id rotation highlights - acunatural family...
TRANSCRIPT
ID Rotation HighlightsAMANDEEP RAKHRA PGY 1
TOAN NGUYEN PGY 2
Typical schedule
Monday Roundsconsults travel clinic
Tuesday AM roundsconsults PM clinic
Wednesday Board review with fellows roundsconsults
Thursday city wide case conference AM roundsclinic PM clinic
Friday AM Fellow clinic at the VA roundsconsults
Tips
Consists of inpatient and outpatient exposure
Utilize free time to study review antibiotics guidelines
Remember to communicate recommendations to primary teams
Helpful resources
Sanford microbiology guide
IDSA website
ID MKSAP
Send your presentation to the fellows for them to look over it prior to
your presentation
Case Conference
You will have opportunity to present at one conference during the
month regarding an interesting case that was seen
The presentation is roughly 30 min long
Helpful to include studies and trials that pertain to your topic
There are specific guidelines when presenting that your fellow will
help you with
Send your presentation to the fellows for them to look over it prior to
your presentation
ID case conference rules
Donrsquot wait til the last minute Working with the fellow and myself pick a
case early Start working on it early
You need to rehearse your presentation with the attending and
fellow Allow time for this You may need to revise your presentation after
the rehearsal
Arrive early at the presentation room You may need to call audiovisual for
help in getting the computer and projector to work
Start on time Finish on time People have other meetings to go to
If you involve a pathologist or radiologist coordinate the
presentations Donrsquot waste time fumbling as you switch from one
presentation
Allow 10 minutes for questions after your presentation ends
ID case conference rules
The VA bans the use of flash drives (thumb drives) E-mail your presentation
for back-up
When you make PowerPoint slides save in an older PowerPoint version
rather than PowerPoint 2007 (unless you know the computer in the
presentation room will handle PowerPoint 2007) That will accommodate
non-upgraded machines
Make back-up copies of your presentation
Always bring a hard copy of your presentation on paper That way you can
continue your presentation even if the computer and projector fail
Use Arial font Other fonts may be hard to read or may be mishandled by
the computer in the presentation room
ID case conference rules
Use white letters on a blue background You may also choose to use black
letters on a white background Other colors may be hard to read
No use of red This cannot be seen by individuals who are color blind
Do not use a template with various pictures or designs This is distracting
If you jam so much material on your slides that no one can read them
yoursquove wasted your time and ours 8 lines maximumslide I donrsquot want to
hear anyone say ldquoThis is a busy sliderdquo If therersquos too much material on a
slide donrsquot apologize Be kind to your audience Redo the slide
8 lines includes ALL lines That includes title and reference
ID case conference rules
Do not use tiny fonts for the reference
Put the relevant reference(s) on each slide In a published paper
references go at the end In a presentation they go on each slide
Try very hard to get pictures Work with us on borrowing a camera getting
x-rays etc Donrsquot wait til the last minute
Do not simply parrot a textbook chapter or a pair of review articles Work
with us to avoid this
Do not cut and paste a table from UpToDatecom These do not project
well If you need to use information from a table you need to retype it If
the table has too much material for one slide revise it and put the
information on two slides
Sample of a good ID case
presentation
ID City Wide Conference
Manasa Velagapudi MBBS
3917
bull No conflicts of interest
bull No discussion of ldquooff-labelrdquo use of medications
Case
Chief Complaint scrotal pain
History of Present Illness
bull 66 yo male who presented to ER with
bull malaise and
bull a 2 day history of diarrhea
bull He has cough with hemoptysis for the last 2 days
bull His exercise capacity has been reduced acutely usually walks a mile to work but has been winded easily He has been coughing up green sputum in addition to the blood
Case(contd)
Past Medical History
bull Diabetes mellitus
Case(contd)
bull Past Surgical History Hernia repair
bull Allergies No known allergies
Case(contd)
Family history
Social History
bull Lives at Sienna Francis shelter
bull Single
bull Never smoker
bull Occasional alcoholic
bull Denies Injection drug use
Case(contd)
Social History
bull No pets
bull No recent travel
Review of systems
bull Constitutional positive for generalized weakness fever
bull Respiratory positive for cough hemoptysis
bull CVS no chest pain dyspnea
bull GI no nausea vomiting diarrhea
bull GU
bull Musculoskeletal negative for arthralgias
Review of systems
bull He denied any CP SOB DOE or palpitations
bull He also denied fevers chills
bull time He also has diarrhea severe with no blood in stool He denies nausea vomiting or abdominal pain
bull lost weight over the last weeksmonths
Physical Exam
bull Vitals T-976 H-73 R-18 BP-14070
bull Constitutional well-developed no distress
bull Eyes Conjunctivae normal
bull HENT poor dentition
bull MouthThroat Oropharynx is clear moist
bull Neck no thyromegaly
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Typical schedule
Monday Roundsconsults travel clinic
Tuesday AM roundsconsults PM clinic
Wednesday Board review with fellows roundsconsults
Thursday city wide case conference AM roundsclinic PM clinic
Friday AM Fellow clinic at the VA roundsconsults
Tips
Consists of inpatient and outpatient exposure
Utilize free time to study review antibiotics guidelines
Remember to communicate recommendations to primary teams
Helpful resources
Sanford microbiology guide
IDSA website
ID MKSAP
Send your presentation to the fellows for them to look over it prior to
your presentation
Case Conference
You will have opportunity to present at one conference during the
month regarding an interesting case that was seen
The presentation is roughly 30 min long
Helpful to include studies and trials that pertain to your topic
There are specific guidelines when presenting that your fellow will
help you with
Send your presentation to the fellows for them to look over it prior to
your presentation
ID case conference rules
Donrsquot wait til the last minute Working with the fellow and myself pick a
case early Start working on it early
You need to rehearse your presentation with the attending and
fellow Allow time for this You may need to revise your presentation after
the rehearsal
Arrive early at the presentation room You may need to call audiovisual for
help in getting the computer and projector to work
Start on time Finish on time People have other meetings to go to
If you involve a pathologist or radiologist coordinate the
presentations Donrsquot waste time fumbling as you switch from one
presentation
Allow 10 minutes for questions after your presentation ends
ID case conference rules
The VA bans the use of flash drives (thumb drives) E-mail your presentation
for back-up
When you make PowerPoint slides save in an older PowerPoint version
rather than PowerPoint 2007 (unless you know the computer in the
presentation room will handle PowerPoint 2007) That will accommodate
non-upgraded machines
Make back-up copies of your presentation
Always bring a hard copy of your presentation on paper That way you can
continue your presentation even if the computer and projector fail
Use Arial font Other fonts may be hard to read or may be mishandled by
the computer in the presentation room
ID case conference rules
Use white letters on a blue background You may also choose to use black
letters on a white background Other colors may be hard to read
No use of red This cannot be seen by individuals who are color blind
Do not use a template with various pictures or designs This is distracting
If you jam so much material on your slides that no one can read them
yoursquove wasted your time and ours 8 lines maximumslide I donrsquot want to
hear anyone say ldquoThis is a busy sliderdquo If therersquos too much material on a
slide donrsquot apologize Be kind to your audience Redo the slide
8 lines includes ALL lines That includes title and reference
ID case conference rules
Do not use tiny fonts for the reference
Put the relevant reference(s) on each slide In a published paper
references go at the end In a presentation they go on each slide
Try very hard to get pictures Work with us on borrowing a camera getting
x-rays etc Donrsquot wait til the last minute
Do not simply parrot a textbook chapter or a pair of review articles Work
with us to avoid this
Do not cut and paste a table from UpToDatecom These do not project
well If you need to use information from a table you need to retype it If
the table has too much material for one slide revise it and put the
information on two slides
Sample of a good ID case
presentation
ID City Wide Conference
Manasa Velagapudi MBBS
3917
bull No conflicts of interest
bull No discussion of ldquooff-labelrdquo use of medications
Case
Chief Complaint scrotal pain
History of Present Illness
bull 66 yo male who presented to ER with
bull malaise and
bull a 2 day history of diarrhea
bull He has cough with hemoptysis for the last 2 days
bull His exercise capacity has been reduced acutely usually walks a mile to work but has been winded easily He has been coughing up green sputum in addition to the blood
Case(contd)
Past Medical History
bull Diabetes mellitus
Case(contd)
bull Past Surgical History Hernia repair
bull Allergies No known allergies
Case(contd)
Family history
Social History
bull Lives at Sienna Francis shelter
bull Single
bull Never smoker
bull Occasional alcoholic
bull Denies Injection drug use
Case(contd)
Social History
bull No pets
bull No recent travel
Review of systems
bull Constitutional positive for generalized weakness fever
bull Respiratory positive for cough hemoptysis
bull CVS no chest pain dyspnea
bull GI no nausea vomiting diarrhea
bull GU
bull Musculoskeletal negative for arthralgias
Review of systems
bull He denied any CP SOB DOE or palpitations
bull He also denied fevers chills
bull time He also has diarrhea severe with no blood in stool He denies nausea vomiting or abdominal pain
bull lost weight over the last weeksmonths
Physical Exam
bull Vitals T-976 H-73 R-18 BP-14070
bull Constitutional well-developed no distress
bull Eyes Conjunctivae normal
bull HENT poor dentition
bull MouthThroat Oropharynx is clear moist
bull Neck no thyromegaly
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Tips
Consists of inpatient and outpatient exposure
Utilize free time to study review antibiotics guidelines
Remember to communicate recommendations to primary teams
Helpful resources
Sanford microbiology guide
IDSA website
ID MKSAP
Send your presentation to the fellows for them to look over it prior to
your presentation
Case Conference
You will have opportunity to present at one conference during the
month regarding an interesting case that was seen
The presentation is roughly 30 min long
Helpful to include studies and trials that pertain to your topic
There are specific guidelines when presenting that your fellow will
help you with
Send your presentation to the fellows for them to look over it prior to
your presentation
ID case conference rules
Donrsquot wait til the last minute Working with the fellow and myself pick a
case early Start working on it early
You need to rehearse your presentation with the attending and
fellow Allow time for this You may need to revise your presentation after
the rehearsal
Arrive early at the presentation room You may need to call audiovisual for
help in getting the computer and projector to work
Start on time Finish on time People have other meetings to go to
If you involve a pathologist or radiologist coordinate the
presentations Donrsquot waste time fumbling as you switch from one
presentation
Allow 10 minutes for questions after your presentation ends
ID case conference rules
The VA bans the use of flash drives (thumb drives) E-mail your presentation
for back-up
When you make PowerPoint slides save in an older PowerPoint version
rather than PowerPoint 2007 (unless you know the computer in the
presentation room will handle PowerPoint 2007) That will accommodate
non-upgraded machines
Make back-up copies of your presentation
Always bring a hard copy of your presentation on paper That way you can
continue your presentation even if the computer and projector fail
Use Arial font Other fonts may be hard to read or may be mishandled by
the computer in the presentation room
ID case conference rules
Use white letters on a blue background You may also choose to use black
letters on a white background Other colors may be hard to read
No use of red This cannot be seen by individuals who are color blind
Do not use a template with various pictures or designs This is distracting
If you jam so much material on your slides that no one can read them
yoursquove wasted your time and ours 8 lines maximumslide I donrsquot want to
hear anyone say ldquoThis is a busy sliderdquo If therersquos too much material on a
slide donrsquot apologize Be kind to your audience Redo the slide
8 lines includes ALL lines That includes title and reference
ID case conference rules
Do not use tiny fonts for the reference
Put the relevant reference(s) on each slide In a published paper
references go at the end In a presentation they go on each slide
Try very hard to get pictures Work with us on borrowing a camera getting
x-rays etc Donrsquot wait til the last minute
Do not simply parrot a textbook chapter or a pair of review articles Work
with us to avoid this
Do not cut and paste a table from UpToDatecom These do not project
well If you need to use information from a table you need to retype it If
the table has too much material for one slide revise it and put the
information on two slides
Sample of a good ID case
presentation
ID City Wide Conference
Manasa Velagapudi MBBS
3917
bull No conflicts of interest
bull No discussion of ldquooff-labelrdquo use of medications
Case
Chief Complaint scrotal pain
History of Present Illness
bull 66 yo male who presented to ER with
bull malaise and
bull a 2 day history of diarrhea
bull He has cough with hemoptysis for the last 2 days
bull His exercise capacity has been reduced acutely usually walks a mile to work but has been winded easily He has been coughing up green sputum in addition to the blood
Case(contd)
Past Medical History
bull Diabetes mellitus
Case(contd)
bull Past Surgical History Hernia repair
bull Allergies No known allergies
Case(contd)
Family history
Social History
bull Lives at Sienna Francis shelter
bull Single
bull Never smoker
bull Occasional alcoholic
bull Denies Injection drug use
Case(contd)
Social History
bull No pets
bull No recent travel
Review of systems
bull Constitutional positive for generalized weakness fever
bull Respiratory positive for cough hemoptysis
bull CVS no chest pain dyspnea
bull GI no nausea vomiting diarrhea
bull GU
bull Musculoskeletal negative for arthralgias
Review of systems
bull He denied any CP SOB DOE or palpitations
bull He also denied fevers chills
bull time He also has diarrhea severe with no blood in stool He denies nausea vomiting or abdominal pain
bull lost weight over the last weeksmonths
Physical Exam
bull Vitals T-976 H-73 R-18 BP-14070
bull Constitutional well-developed no distress
bull Eyes Conjunctivae normal
bull HENT poor dentition
bull MouthThroat Oropharynx is clear moist
bull Neck no thyromegaly
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Case Conference
You will have opportunity to present at one conference during the
month regarding an interesting case that was seen
The presentation is roughly 30 min long
Helpful to include studies and trials that pertain to your topic
There are specific guidelines when presenting that your fellow will
help you with
Send your presentation to the fellows for them to look over it prior to
your presentation
ID case conference rules
Donrsquot wait til the last minute Working with the fellow and myself pick a
case early Start working on it early
You need to rehearse your presentation with the attending and
fellow Allow time for this You may need to revise your presentation after
the rehearsal
Arrive early at the presentation room You may need to call audiovisual for
help in getting the computer and projector to work
Start on time Finish on time People have other meetings to go to
If you involve a pathologist or radiologist coordinate the
presentations Donrsquot waste time fumbling as you switch from one
presentation
Allow 10 minutes for questions after your presentation ends
ID case conference rules
The VA bans the use of flash drives (thumb drives) E-mail your presentation
for back-up
When you make PowerPoint slides save in an older PowerPoint version
rather than PowerPoint 2007 (unless you know the computer in the
presentation room will handle PowerPoint 2007) That will accommodate
non-upgraded machines
Make back-up copies of your presentation
Always bring a hard copy of your presentation on paper That way you can
continue your presentation even if the computer and projector fail
Use Arial font Other fonts may be hard to read or may be mishandled by
the computer in the presentation room
ID case conference rules
Use white letters on a blue background You may also choose to use black
letters on a white background Other colors may be hard to read
No use of red This cannot be seen by individuals who are color blind
Do not use a template with various pictures or designs This is distracting
If you jam so much material on your slides that no one can read them
yoursquove wasted your time and ours 8 lines maximumslide I donrsquot want to
hear anyone say ldquoThis is a busy sliderdquo If therersquos too much material on a
slide donrsquot apologize Be kind to your audience Redo the slide
8 lines includes ALL lines That includes title and reference
ID case conference rules
Do not use tiny fonts for the reference
Put the relevant reference(s) on each slide In a published paper
references go at the end In a presentation they go on each slide
Try very hard to get pictures Work with us on borrowing a camera getting
x-rays etc Donrsquot wait til the last minute
Do not simply parrot a textbook chapter or a pair of review articles Work
with us to avoid this
Do not cut and paste a table from UpToDatecom These do not project
well If you need to use information from a table you need to retype it If
the table has too much material for one slide revise it and put the
information on two slides
Sample of a good ID case
presentation
ID City Wide Conference
Manasa Velagapudi MBBS
3917
bull No conflicts of interest
bull No discussion of ldquooff-labelrdquo use of medications
Case
Chief Complaint scrotal pain
History of Present Illness
bull 66 yo male who presented to ER with
bull malaise and
bull a 2 day history of diarrhea
bull He has cough with hemoptysis for the last 2 days
bull His exercise capacity has been reduced acutely usually walks a mile to work but has been winded easily He has been coughing up green sputum in addition to the blood
Case(contd)
Past Medical History
bull Diabetes mellitus
Case(contd)
bull Past Surgical History Hernia repair
bull Allergies No known allergies
Case(contd)
Family history
Social History
bull Lives at Sienna Francis shelter
bull Single
bull Never smoker
bull Occasional alcoholic
bull Denies Injection drug use
Case(contd)
Social History
bull No pets
bull No recent travel
Review of systems
bull Constitutional positive for generalized weakness fever
bull Respiratory positive for cough hemoptysis
bull CVS no chest pain dyspnea
bull GI no nausea vomiting diarrhea
bull GU
bull Musculoskeletal negative for arthralgias
Review of systems
bull He denied any CP SOB DOE or palpitations
bull He also denied fevers chills
bull time He also has diarrhea severe with no blood in stool He denies nausea vomiting or abdominal pain
bull lost weight over the last weeksmonths
Physical Exam
bull Vitals T-976 H-73 R-18 BP-14070
bull Constitutional well-developed no distress
bull Eyes Conjunctivae normal
bull HENT poor dentition
bull MouthThroat Oropharynx is clear moist
bull Neck no thyromegaly
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
ID case conference rules
Donrsquot wait til the last minute Working with the fellow and myself pick a
case early Start working on it early
You need to rehearse your presentation with the attending and
fellow Allow time for this You may need to revise your presentation after
the rehearsal
Arrive early at the presentation room You may need to call audiovisual for
help in getting the computer and projector to work
Start on time Finish on time People have other meetings to go to
If you involve a pathologist or radiologist coordinate the
presentations Donrsquot waste time fumbling as you switch from one
presentation
Allow 10 minutes for questions after your presentation ends
ID case conference rules
The VA bans the use of flash drives (thumb drives) E-mail your presentation
for back-up
When you make PowerPoint slides save in an older PowerPoint version
rather than PowerPoint 2007 (unless you know the computer in the
presentation room will handle PowerPoint 2007) That will accommodate
non-upgraded machines
Make back-up copies of your presentation
Always bring a hard copy of your presentation on paper That way you can
continue your presentation even if the computer and projector fail
Use Arial font Other fonts may be hard to read or may be mishandled by
the computer in the presentation room
ID case conference rules
Use white letters on a blue background You may also choose to use black
letters on a white background Other colors may be hard to read
No use of red This cannot be seen by individuals who are color blind
Do not use a template with various pictures or designs This is distracting
If you jam so much material on your slides that no one can read them
yoursquove wasted your time and ours 8 lines maximumslide I donrsquot want to
hear anyone say ldquoThis is a busy sliderdquo If therersquos too much material on a
slide donrsquot apologize Be kind to your audience Redo the slide
8 lines includes ALL lines That includes title and reference
ID case conference rules
Do not use tiny fonts for the reference
Put the relevant reference(s) on each slide In a published paper
references go at the end In a presentation they go on each slide
Try very hard to get pictures Work with us on borrowing a camera getting
x-rays etc Donrsquot wait til the last minute
Do not simply parrot a textbook chapter or a pair of review articles Work
with us to avoid this
Do not cut and paste a table from UpToDatecom These do not project
well If you need to use information from a table you need to retype it If
the table has too much material for one slide revise it and put the
information on two slides
Sample of a good ID case
presentation
ID City Wide Conference
Manasa Velagapudi MBBS
3917
bull No conflicts of interest
bull No discussion of ldquooff-labelrdquo use of medications
Case
Chief Complaint scrotal pain
History of Present Illness
bull 66 yo male who presented to ER with
bull malaise and
bull a 2 day history of diarrhea
bull He has cough with hemoptysis for the last 2 days
bull His exercise capacity has been reduced acutely usually walks a mile to work but has been winded easily He has been coughing up green sputum in addition to the blood
Case(contd)
Past Medical History
bull Diabetes mellitus
Case(contd)
bull Past Surgical History Hernia repair
bull Allergies No known allergies
Case(contd)
Family history
Social History
bull Lives at Sienna Francis shelter
bull Single
bull Never smoker
bull Occasional alcoholic
bull Denies Injection drug use
Case(contd)
Social History
bull No pets
bull No recent travel
Review of systems
bull Constitutional positive for generalized weakness fever
bull Respiratory positive for cough hemoptysis
bull CVS no chest pain dyspnea
bull GI no nausea vomiting diarrhea
bull GU
bull Musculoskeletal negative for arthralgias
Review of systems
bull He denied any CP SOB DOE or palpitations
bull He also denied fevers chills
bull time He also has diarrhea severe with no blood in stool He denies nausea vomiting or abdominal pain
bull lost weight over the last weeksmonths
Physical Exam
bull Vitals T-976 H-73 R-18 BP-14070
bull Constitutional well-developed no distress
bull Eyes Conjunctivae normal
bull HENT poor dentition
bull MouthThroat Oropharynx is clear moist
bull Neck no thyromegaly
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
ID case conference rules
The VA bans the use of flash drives (thumb drives) E-mail your presentation
for back-up
When you make PowerPoint slides save in an older PowerPoint version
rather than PowerPoint 2007 (unless you know the computer in the
presentation room will handle PowerPoint 2007) That will accommodate
non-upgraded machines
Make back-up copies of your presentation
Always bring a hard copy of your presentation on paper That way you can
continue your presentation even if the computer and projector fail
Use Arial font Other fonts may be hard to read or may be mishandled by
the computer in the presentation room
ID case conference rules
Use white letters on a blue background You may also choose to use black
letters on a white background Other colors may be hard to read
No use of red This cannot be seen by individuals who are color blind
Do not use a template with various pictures or designs This is distracting
If you jam so much material on your slides that no one can read them
yoursquove wasted your time and ours 8 lines maximumslide I donrsquot want to
hear anyone say ldquoThis is a busy sliderdquo If therersquos too much material on a
slide donrsquot apologize Be kind to your audience Redo the slide
8 lines includes ALL lines That includes title and reference
ID case conference rules
Do not use tiny fonts for the reference
Put the relevant reference(s) on each slide In a published paper
references go at the end In a presentation they go on each slide
Try very hard to get pictures Work with us on borrowing a camera getting
x-rays etc Donrsquot wait til the last minute
Do not simply parrot a textbook chapter or a pair of review articles Work
with us to avoid this
Do not cut and paste a table from UpToDatecom These do not project
well If you need to use information from a table you need to retype it If
the table has too much material for one slide revise it and put the
information on two slides
Sample of a good ID case
presentation
ID City Wide Conference
Manasa Velagapudi MBBS
3917
bull No conflicts of interest
bull No discussion of ldquooff-labelrdquo use of medications
Case
Chief Complaint scrotal pain
History of Present Illness
bull 66 yo male who presented to ER with
bull malaise and
bull a 2 day history of diarrhea
bull He has cough with hemoptysis for the last 2 days
bull His exercise capacity has been reduced acutely usually walks a mile to work but has been winded easily He has been coughing up green sputum in addition to the blood
Case(contd)
Past Medical History
bull Diabetes mellitus
Case(contd)
bull Past Surgical History Hernia repair
bull Allergies No known allergies
Case(contd)
Family history
Social History
bull Lives at Sienna Francis shelter
bull Single
bull Never smoker
bull Occasional alcoholic
bull Denies Injection drug use
Case(contd)
Social History
bull No pets
bull No recent travel
Review of systems
bull Constitutional positive for generalized weakness fever
bull Respiratory positive for cough hemoptysis
bull CVS no chest pain dyspnea
bull GI no nausea vomiting diarrhea
bull GU
bull Musculoskeletal negative for arthralgias
Review of systems
bull He denied any CP SOB DOE or palpitations
bull He also denied fevers chills
bull time He also has diarrhea severe with no blood in stool He denies nausea vomiting or abdominal pain
bull lost weight over the last weeksmonths
Physical Exam
bull Vitals T-976 H-73 R-18 BP-14070
bull Constitutional well-developed no distress
bull Eyes Conjunctivae normal
bull HENT poor dentition
bull MouthThroat Oropharynx is clear moist
bull Neck no thyromegaly
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
ID case conference rules
Use white letters on a blue background You may also choose to use black
letters on a white background Other colors may be hard to read
No use of red This cannot be seen by individuals who are color blind
Do not use a template with various pictures or designs This is distracting
If you jam so much material on your slides that no one can read them
yoursquove wasted your time and ours 8 lines maximumslide I donrsquot want to
hear anyone say ldquoThis is a busy sliderdquo If therersquos too much material on a
slide donrsquot apologize Be kind to your audience Redo the slide
8 lines includes ALL lines That includes title and reference
ID case conference rules
Do not use tiny fonts for the reference
Put the relevant reference(s) on each slide In a published paper
references go at the end In a presentation they go on each slide
Try very hard to get pictures Work with us on borrowing a camera getting
x-rays etc Donrsquot wait til the last minute
Do not simply parrot a textbook chapter or a pair of review articles Work
with us to avoid this
Do not cut and paste a table from UpToDatecom These do not project
well If you need to use information from a table you need to retype it If
the table has too much material for one slide revise it and put the
information on two slides
Sample of a good ID case
presentation
ID City Wide Conference
Manasa Velagapudi MBBS
3917
bull No conflicts of interest
bull No discussion of ldquooff-labelrdquo use of medications
Case
Chief Complaint scrotal pain
History of Present Illness
bull 66 yo male who presented to ER with
bull malaise and
bull a 2 day history of diarrhea
bull He has cough with hemoptysis for the last 2 days
bull His exercise capacity has been reduced acutely usually walks a mile to work but has been winded easily He has been coughing up green sputum in addition to the blood
Case(contd)
Past Medical History
bull Diabetes mellitus
Case(contd)
bull Past Surgical History Hernia repair
bull Allergies No known allergies
Case(contd)
Family history
Social History
bull Lives at Sienna Francis shelter
bull Single
bull Never smoker
bull Occasional alcoholic
bull Denies Injection drug use
Case(contd)
Social History
bull No pets
bull No recent travel
Review of systems
bull Constitutional positive for generalized weakness fever
bull Respiratory positive for cough hemoptysis
bull CVS no chest pain dyspnea
bull GI no nausea vomiting diarrhea
bull GU
bull Musculoskeletal negative for arthralgias
Review of systems
bull He denied any CP SOB DOE or palpitations
bull He also denied fevers chills
bull time He also has diarrhea severe with no blood in stool He denies nausea vomiting or abdominal pain
bull lost weight over the last weeksmonths
Physical Exam
bull Vitals T-976 H-73 R-18 BP-14070
bull Constitutional well-developed no distress
bull Eyes Conjunctivae normal
bull HENT poor dentition
bull MouthThroat Oropharynx is clear moist
bull Neck no thyromegaly
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
ID case conference rules
Do not use tiny fonts for the reference
Put the relevant reference(s) on each slide In a published paper
references go at the end In a presentation they go on each slide
Try very hard to get pictures Work with us on borrowing a camera getting
x-rays etc Donrsquot wait til the last minute
Do not simply parrot a textbook chapter or a pair of review articles Work
with us to avoid this
Do not cut and paste a table from UpToDatecom These do not project
well If you need to use information from a table you need to retype it If
the table has too much material for one slide revise it and put the
information on two slides
Sample of a good ID case
presentation
ID City Wide Conference
Manasa Velagapudi MBBS
3917
bull No conflicts of interest
bull No discussion of ldquooff-labelrdquo use of medications
Case
Chief Complaint scrotal pain
History of Present Illness
bull 66 yo male who presented to ER with
bull malaise and
bull a 2 day history of diarrhea
bull He has cough with hemoptysis for the last 2 days
bull His exercise capacity has been reduced acutely usually walks a mile to work but has been winded easily He has been coughing up green sputum in addition to the blood
Case(contd)
Past Medical History
bull Diabetes mellitus
Case(contd)
bull Past Surgical History Hernia repair
bull Allergies No known allergies
Case(contd)
Family history
Social History
bull Lives at Sienna Francis shelter
bull Single
bull Never smoker
bull Occasional alcoholic
bull Denies Injection drug use
Case(contd)
Social History
bull No pets
bull No recent travel
Review of systems
bull Constitutional positive for generalized weakness fever
bull Respiratory positive for cough hemoptysis
bull CVS no chest pain dyspnea
bull GI no nausea vomiting diarrhea
bull GU
bull Musculoskeletal negative for arthralgias
Review of systems
bull He denied any CP SOB DOE or palpitations
bull He also denied fevers chills
bull time He also has diarrhea severe with no blood in stool He denies nausea vomiting or abdominal pain
bull lost weight over the last weeksmonths
Physical Exam
bull Vitals T-976 H-73 R-18 BP-14070
bull Constitutional well-developed no distress
bull Eyes Conjunctivae normal
bull HENT poor dentition
bull MouthThroat Oropharynx is clear moist
bull Neck no thyromegaly
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Sample of a good ID case
presentation
ID City Wide Conference
Manasa Velagapudi MBBS
3917
bull No conflicts of interest
bull No discussion of ldquooff-labelrdquo use of medications
Case
Chief Complaint scrotal pain
History of Present Illness
bull 66 yo male who presented to ER with
bull malaise and
bull a 2 day history of diarrhea
bull He has cough with hemoptysis for the last 2 days
bull His exercise capacity has been reduced acutely usually walks a mile to work but has been winded easily He has been coughing up green sputum in addition to the blood
Case(contd)
Past Medical History
bull Diabetes mellitus
Case(contd)
bull Past Surgical History Hernia repair
bull Allergies No known allergies
Case(contd)
Family history
Social History
bull Lives at Sienna Francis shelter
bull Single
bull Never smoker
bull Occasional alcoholic
bull Denies Injection drug use
Case(contd)
Social History
bull No pets
bull No recent travel
Review of systems
bull Constitutional positive for generalized weakness fever
bull Respiratory positive for cough hemoptysis
bull CVS no chest pain dyspnea
bull GI no nausea vomiting diarrhea
bull GU
bull Musculoskeletal negative for arthralgias
Review of systems
bull He denied any CP SOB DOE or palpitations
bull He also denied fevers chills
bull time He also has diarrhea severe with no blood in stool He denies nausea vomiting or abdominal pain
bull lost weight over the last weeksmonths
Physical Exam
bull Vitals T-976 H-73 R-18 BP-14070
bull Constitutional well-developed no distress
bull Eyes Conjunctivae normal
bull HENT poor dentition
bull MouthThroat Oropharynx is clear moist
bull Neck no thyromegaly
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
ID City Wide Conference
Manasa Velagapudi MBBS
3917
bull No conflicts of interest
bull No discussion of ldquooff-labelrdquo use of medications
Case
Chief Complaint scrotal pain
History of Present Illness
bull 66 yo male who presented to ER with
bull malaise and
bull a 2 day history of diarrhea
bull He has cough with hemoptysis for the last 2 days
bull His exercise capacity has been reduced acutely usually walks a mile to work but has been winded easily He has been coughing up green sputum in addition to the blood
Case(contd)
Past Medical History
bull Diabetes mellitus
Case(contd)
bull Past Surgical History Hernia repair
bull Allergies No known allergies
Case(contd)
Family history
Social History
bull Lives at Sienna Francis shelter
bull Single
bull Never smoker
bull Occasional alcoholic
bull Denies Injection drug use
Case(contd)
Social History
bull No pets
bull No recent travel
Review of systems
bull Constitutional positive for generalized weakness fever
bull Respiratory positive for cough hemoptysis
bull CVS no chest pain dyspnea
bull GI no nausea vomiting diarrhea
bull GU
bull Musculoskeletal negative for arthralgias
Review of systems
bull He denied any CP SOB DOE or palpitations
bull He also denied fevers chills
bull time He also has diarrhea severe with no blood in stool He denies nausea vomiting or abdominal pain
bull lost weight over the last weeksmonths
Physical Exam
bull Vitals T-976 H-73 R-18 BP-14070
bull Constitutional well-developed no distress
bull Eyes Conjunctivae normal
bull HENT poor dentition
bull MouthThroat Oropharynx is clear moist
bull Neck no thyromegaly
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
bull No conflicts of interest
bull No discussion of ldquooff-labelrdquo use of medications
Case
Chief Complaint scrotal pain
History of Present Illness
bull 66 yo male who presented to ER with
bull malaise and
bull a 2 day history of diarrhea
bull He has cough with hemoptysis for the last 2 days
bull His exercise capacity has been reduced acutely usually walks a mile to work but has been winded easily He has been coughing up green sputum in addition to the blood
Case(contd)
Past Medical History
bull Diabetes mellitus
Case(contd)
bull Past Surgical History Hernia repair
bull Allergies No known allergies
Case(contd)
Family history
Social History
bull Lives at Sienna Francis shelter
bull Single
bull Never smoker
bull Occasional alcoholic
bull Denies Injection drug use
Case(contd)
Social History
bull No pets
bull No recent travel
Review of systems
bull Constitutional positive for generalized weakness fever
bull Respiratory positive for cough hemoptysis
bull CVS no chest pain dyspnea
bull GI no nausea vomiting diarrhea
bull GU
bull Musculoskeletal negative for arthralgias
Review of systems
bull He denied any CP SOB DOE or palpitations
bull He also denied fevers chills
bull time He also has diarrhea severe with no blood in stool He denies nausea vomiting or abdominal pain
bull lost weight over the last weeksmonths
Physical Exam
bull Vitals T-976 H-73 R-18 BP-14070
bull Constitutional well-developed no distress
bull Eyes Conjunctivae normal
bull HENT poor dentition
bull MouthThroat Oropharynx is clear moist
bull Neck no thyromegaly
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Case
Chief Complaint scrotal pain
History of Present Illness
bull 66 yo male who presented to ER with
bull malaise and
bull a 2 day history of diarrhea
bull He has cough with hemoptysis for the last 2 days
bull His exercise capacity has been reduced acutely usually walks a mile to work but has been winded easily He has been coughing up green sputum in addition to the blood
Case(contd)
Past Medical History
bull Diabetes mellitus
Case(contd)
bull Past Surgical History Hernia repair
bull Allergies No known allergies
Case(contd)
Family history
Social History
bull Lives at Sienna Francis shelter
bull Single
bull Never smoker
bull Occasional alcoholic
bull Denies Injection drug use
Case(contd)
Social History
bull No pets
bull No recent travel
Review of systems
bull Constitutional positive for generalized weakness fever
bull Respiratory positive for cough hemoptysis
bull CVS no chest pain dyspnea
bull GI no nausea vomiting diarrhea
bull GU
bull Musculoskeletal negative for arthralgias
Review of systems
bull He denied any CP SOB DOE or palpitations
bull He also denied fevers chills
bull time He also has diarrhea severe with no blood in stool He denies nausea vomiting or abdominal pain
bull lost weight over the last weeksmonths
Physical Exam
bull Vitals T-976 H-73 R-18 BP-14070
bull Constitutional well-developed no distress
bull Eyes Conjunctivae normal
bull HENT poor dentition
bull MouthThroat Oropharynx is clear moist
bull Neck no thyromegaly
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Case(contd)
Past Medical History
bull Diabetes mellitus
Case(contd)
bull Past Surgical History Hernia repair
bull Allergies No known allergies
Case(contd)
Family history
Social History
bull Lives at Sienna Francis shelter
bull Single
bull Never smoker
bull Occasional alcoholic
bull Denies Injection drug use
Case(contd)
Social History
bull No pets
bull No recent travel
Review of systems
bull Constitutional positive for generalized weakness fever
bull Respiratory positive for cough hemoptysis
bull CVS no chest pain dyspnea
bull GI no nausea vomiting diarrhea
bull GU
bull Musculoskeletal negative for arthralgias
Review of systems
bull He denied any CP SOB DOE or palpitations
bull He also denied fevers chills
bull time He also has diarrhea severe with no blood in stool He denies nausea vomiting or abdominal pain
bull lost weight over the last weeksmonths
Physical Exam
bull Vitals T-976 H-73 R-18 BP-14070
bull Constitutional well-developed no distress
bull Eyes Conjunctivae normal
bull HENT poor dentition
bull MouthThroat Oropharynx is clear moist
bull Neck no thyromegaly
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Case(contd)
bull Past Surgical History Hernia repair
bull Allergies No known allergies
Case(contd)
Family history
Social History
bull Lives at Sienna Francis shelter
bull Single
bull Never smoker
bull Occasional alcoholic
bull Denies Injection drug use
Case(contd)
Social History
bull No pets
bull No recent travel
Review of systems
bull Constitutional positive for generalized weakness fever
bull Respiratory positive for cough hemoptysis
bull CVS no chest pain dyspnea
bull GI no nausea vomiting diarrhea
bull GU
bull Musculoskeletal negative for arthralgias
Review of systems
bull He denied any CP SOB DOE or palpitations
bull He also denied fevers chills
bull time He also has diarrhea severe with no blood in stool He denies nausea vomiting or abdominal pain
bull lost weight over the last weeksmonths
Physical Exam
bull Vitals T-976 H-73 R-18 BP-14070
bull Constitutional well-developed no distress
bull Eyes Conjunctivae normal
bull HENT poor dentition
bull MouthThroat Oropharynx is clear moist
bull Neck no thyromegaly
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Case(contd)
Family history
Social History
bull Lives at Sienna Francis shelter
bull Single
bull Never smoker
bull Occasional alcoholic
bull Denies Injection drug use
Case(contd)
Social History
bull No pets
bull No recent travel
Review of systems
bull Constitutional positive for generalized weakness fever
bull Respiratory positive for cough hemoptysis
bull CVS no chest pain dyspnea
bull GI no nausea vomiting diarrhea
bull GU
bull Musculoskeletal negative for arthralgias
Review of systems
bull He denied any CP SOB DOE or palpitations
bull He also denied fevers chills
bull time He also has diarrhea severe with no blood in stool He denies nausea vomiting or abdominal pain
bull lost weight over the last weeksmonths
Physical Exam
bull Vitals T-976 H-73 R-18 BP-14070
bull Constitutional well-developed no distress
bull Eyes Conjunctivae normal
bull HENT poor dentition
bull MouthThroat Oropharynx is clear moist
bull Neck no thyromegaly
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Case(contd)
Social History
bull No pets
bull No recent travel
Review of systems
bull Constitutional positive for generalized weakness fever
bull Respiratory positive for cough hemoptysis
bull CVS no chest pain dyspnea
bull GI no nausea vomiting diarrhea
bull GU
bull Musculoskeletal negative for arthralgias
Review of systems
bull He denied any CP SOB DOE or palpitations
bull He also denied fevers chills
bull time He also has diarrhea severe with no blood in stool He denies nausea vomiting or abdominal pain
bull lost weight over the last weeksmonths
Physical Exam
bull Vitals T-976 H-73 R-18 BP-14070
bull Constitutional well-developed no distress
bull Eyes Conjunctivae normal
bull HENT poor dentition
bull MouthThroat Oropharynx is clear moist
bull Neck no thyromegaly
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Review of systems
bull Constitutional positive for generalized weakness fever
bull Respiratory positive for cough hemoptysis
bull CVS no chest pain dyspnea
bull GI no nausea vomiting diarrhea
bull GU
bull Musculoskeletal negative for arthralgias
Review of systems
bull He denied any CP SOB DOE or palpitations
bull He also denied fevers chills
bull time He also has diarrhea severe with no blood in stool He denies nausea vomiting or abdominal pain
bull lost weight over the last weeksmonths
Physical Exam
bull Vitals T-976 H-73 R-18 BP-14070
bull Constitutional well-developed no distress
bull Eyes Conjunctivae normal
bull HENT poor dentition
bull MouthThroat Oropharynx is clear moist
bull Neck no thyromegaly
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Review of systems
bull He denied any CP SOB DOE or palpitations
bull He also denied fevers chills
bull time He also has diarrhea severe with no blood in stool He denies nausea vomiting or abdominal pain
bull lost weight over the last weeksmonths
Physical Exam
bull Vitals T-976 H-73 R-18 BP-14070
bull Constitutional well-developed no distress
bull Eyes Conjunctivae normal
bull HENT poor dentition
bull MouthThroat Oropharynx is clear moist
bull Neck no thyromegaly
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Physical Exam
bull Vitals T-976 H-73 R-18 BP-14070
bull Constitutional well-developed no distress
bull Eyes Conjunctivae normal
bull HENT poor dentition
bull MouthThroat Oropharynx is clear moist
bull Neck no thyromegaly
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Physical Exam
bull GI Soft non-tender and Bowel sounds present
bull GU Swollen tender scrotumpustule-4x2 cm palpable
penile pristhesis
bull Skin no rash
bull CNS no focal deficits
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Diagnostics
bull Hb- 123
bull WBC-107 with normal diff
bull Platelets-137
bull Creatinine-111
bull INR - 10
bull LFTS-normal
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Diagnostics
bull Alcohol-negative
bull Urine drug screen-negative
bull Chest xray No cardiopulmonary infiltrate
bull UA ndashno pyuria bacteruria
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Further Course
bull 2 weeks later
bull persistent pain
bull scrotal swelling
bull erosion of overlying skin
bull exposed penile implant
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Case Summary
bull 69 year old male with a inflatable penile implant with
scrotal swelling pain and exposed implant
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Diagnostics
Microbiology
bull 2 out of 2 blood cultures- no growth
bull scrotal drainage culture
Group B Streptococcus- 3+
Coagulase negative Staphylococcus- rare
Diptheroids
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Acinetobacter baumannii
bull gram-negative coccobacillus
bull strictly aerobic
bull glucose nonfermenter
bull catalase-positive oxidase-negative bacteria
bull found in water and soil
bull colonises skinwounds respiratory and GI tract
Clin Microbiol Rev 200721538
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Epidemiology
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Who are at risk
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
bull The virulence of this pathogen is enhanced by the frequent development of multiple antimicrobial resistance which severely restricts the therapeutic options
Chest 1999 1151378-82
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
bull ICU patients
bull Burns patiets
bull Low birth weight infants
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Risk Factors for A baumanniiNosocomial Bacteremia in ICU
immunosuppression
unscheduled admission
respiratory failure at admission
previous sepsis in ICU
invasive procedures
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
arterial catheter abdominal drainages central venous catheter mechanical ventilation nasogastric tube peripheral vein catheter pulmonary artery catheter thoracic drain- ageandurinary catheter
CID 200133 944
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Risk Factors for A baumannii Nosocomial Bacteremia in ICU
Male sexAPACHE II score length of stay in ICU mechanical ventilation prior infection bull antimicrobial therapy- cephalosporins and aminoglycosides hasbull been associated with a higher risk of infection or colonizationbull ofthe respiratory tract with A baumannii than with other gramnegativebull bacilli [23]enteral hyperalimentation
Ann Intern Med 1998 129182
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Risk factors
neurosurgery
adult respiratory distress syndrome
head trauma
large-volume pulmonary aspiration
Chest 1997 1121050
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Who else are at risk
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Risk Factors for A baumannii Nosocomial Bacteremia in Adult Burns
bull female sex
bull total body surface of burn gt50
bull prior colonization with AB
bull and use of hydrotherapy
Clin Infect Dis 1999 2859
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
bull Epidemic outbreaks of AB nosocomial infections have developed in different hospital areas but mainly in the ICU
Eur J Clin Microbiol Infect Dis 1988 7485
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Community acquired
Versus
Health care associated Abaumanii
pneumonia
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Cbull First CAP-AB patients were more likely to be
ever-smokers and to have
bull COPD while other lung diseases or comorbid conditionssuch as liver cirrhosis diabetes mellitus
bull malignancy and hematologic malignancy were not predisposing factors Second the clinical presentation
Chest 2006129 107
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
bull CAP-AB group had significantly higher higher mortality than patients in the HAP-AB group bull was more acute and fulminant with the conditionsbull of more patients complicated by ARDS andbull DIC Third CAP-AB patients were likely to have ABbull bacteremia on presentation and were less likely tobull have other concomitant organisms grown in culturebull from the same respiratory specimen Fourth antibioticbull sensitivity was significantly different in the twobull groups with HAP-AB isolates being more resistantbull than the CAP-AB isolates Nevertheless the appropriatebull empirical coverage of CAP-AB did not seembull to alter the dismal prognosis Finally patients in the
Chest 2006129 107
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
bull Finally patients in the
bull CAP-AB group had significantly higher mortality
bull than patients in the HAP-AB group Therefore we
bull propose that CAP-AB is a unique clinical entity
bull characterized by a high incidence of bacteremia
bull ARDS DIC and early deaths
bull Our study showed that CAP-AB usually occur
Chest 2006129 107
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
CAP vs HAP
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
factors were associated with higher mortality in the CAP-AB
AB bacteremia
platelet count of 120 x109cellsL
pH 735 on presentation
and the presenceof DIC
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
bull Lipopolysaccharides may play an important role in the pathogenesis of CAP-AB which may explain its fulminant nature
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Mortality
bull CAP-AB appears to be characterized
bull by a fulminant course with an acute onset of
bull dyspnea cough and fever that rapidly progresses to respiratory failure and shock
Chest2001 1201072ndash1077
bull mortality rate from CAP-AB is high (40 to 64) gtthe overall mortality rate (24)resulting from severe CAP
Chest 1994 1051487ndash1495
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
bull Patients with A baumannii bacteremia
had significantly
bull more hemodynamic instability
bull longer ICU stay and
bull longer ventilator dependence
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Abaumannii bacteremia
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Risk factors of Ab bacteremia
CID 200133 939
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
bull The impact of nosocomial bloodstream infection on the outcome of critically ill patients has been extensively studied with an attributable mortality rate ranging from 19 to 35
Clin Infect Dis 1997 24 387
JAMA 1994 27115
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
bull The nonsignificant attributable mortality in A baumanniibacteremia might be the consequence of a high overall rate of appropriate antibiotic therapy (88) and a short delay in the start of treatment (08―12 days)
Intensive Care Med 200329471
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Intensive Care Med 200329471
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Clinical features
Clinical infections bull pneumoniabull meningitis bull bacteremiabull soft-tissue infections bull surgical site infections bull peritonitis bull endocarditis bull catheter-related and urinary tract infections
Eur J Clin Microbiol Infect Dis 1998 1773
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Sulbactam
bull Sulbactam has been successfully used as a single agent
bull and in combination with ampicillin for the treatment of
bull severe Acinetobacter infections including bacteremia and
bull VAP5816 Its mechanism of antimicrobial activity against
bull A baumannii strains is related to its intrinsic affinity for
bull essential penicillin-binding proteins (PBPs) of these organisms
bull and to alter the permeability of the outer membrane
bull of gram-negative bacilli resulting in the leakage of
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Sulbactam
bull b-lactamases and thus better penetration by other antibacterialbull agentsAntimicrob Agents Chemother2004481586bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
Sulbactam
bull Sulbactam has a good penetration inbull the lower respiratory tract during bacterial pneumoniabull and reaches therapeutically active concentrations in thebull alveolar lining fluid similar to that in serum18 The use ofbull high doses of the drug was based on our previous experience8bull and the knowledge that since sulbactam has timebull dependent activity a high dose could achieve a higherbull t gt MIC which is an important parameter of the in vivobull efficacy of b-lactamaseeb-lactam combination
bull Antimicrob Agents Chemother 2015 59 1680
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
bull It must also be highlighted
bull that the pharmacokinetic and pharmacodynamic benefits of
bull extended-infusion b-lactams attenuate in patients with increasing
bull renal impairment which is a common comorbidity in patients
bull with Acinetobacter infection who are hospitalized in intensive
bull care units
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
bull Finally it is unknown whether the use of
bull extended-infusion carbapenems will reduce the emergence of
bull antibiotic resistance in Acinetobacter
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
bull They found no differencebull in outcomes between the 2 groups however the number ofbull monotherapy patients was small Overall there is far more inbull vitro and in vivo data available than there is data from clinicalbull studies which makes any direct applicability of the data tobull clinical care problematic To summarize the extensive in vitrobull information the most significant data on combination therapybull pertains to colistin and rifampin or a carbapenem [4 39]bull Because of the lack of well-controlled comparative trials ofbull combination therapy for A baumannii infections we cannotbull make any specific recommendations related to the variousbull agents available for therapy
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
bull Diagn
bull Microbiol Infect Dis 2005 52(4)317ndash322
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
CDC Serious Threats
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
bull Nosocomial opportunistic pathogen and frequent cause of ventilator-associated pneumonia with or without associated bacteremia
bull Roughly 50 of Acinetobacterisolates now demonstrate multidrug resistance to include production of ESBLs and carbapenemases ( AntimicrobAgents Chemother 574605 2013 ) Prevalence varies from institution to institution Hence choice of empiric therapy in time period between identification of the pathogen and availability of in vitro susceptibility is difficultndash Choice depends on local antibiogramsndash Severity of the infectionndash Status of the patients immune system
bull Specific (Directed) treatmentregimens are determined by susceptibility of the identified
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
bull There may be resistance to multiple classes of antimicrobials 50 of A baumannii strains from ICUs in the US that are are carbapenem resistant ( Antimicrob Agents Chemother 574605 2013 )
bull Links to specific diseasesconditionsndash Acinetobacter pneumoniandash Acinetobacter meningitisndash Acinetobacter wound infection
bull Classificationbull Gram negative bacilli glucose non-fermenterbull Primary Regimensbull Patients with nosocomial pneumonia and Acinetobacter is carbapenem susceptible
ndash Imipenem 05-1 gm IV q6hor Meropenem 1 gm IVq8h Resistance may develop during therapyndash Ampicillin-sulbactam(Sulbactam is the active component) 3 gm IV q6h (Clin Infect Dis 5179 2010)
bull Patients who are bacteremic from infected IV line or pneumonia or endocarditis and Acinetobacter identified and in vitro susceptibility is pending
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
bull pendingndash Remove the infected line
ndash If local prevalence of carbapenem resistance is lt 20bull Meropenem 1 gm IVq8h + ( Ciprofloxacin400 mg IV q8h orAmp-Sulb 3
gm IVq6h) + Gentamicin51-7 mgkg IV once daily De-escalate when susceptibility results available
ndash If local prevalence of carbapenem resistance is gt 20 andor immunocompromised host
bull Meropenem 1 gm IVq8h plus polymyxin B 25 mgkg IV over 2 hrs as loading dose Then 12 hrs later start 15 mgkg IVover 1 hr and repeat q12h
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
bull For multi-drug resistant (MDR) isolates with in vitro resistanceto all penicillins cephalosporins carbapenems aminoglycosides and fluoroquinolonesndash For critically ill patient with pneumonia andor bacteremia ( Antimicrob Agents
Chemother 553284 2011 Crit Care Med 431194 2015 Crit Care Med 431332 2015 )
ndash Combination therapy with [ Polymyxin B(preferred) or Colistin] + ( Imipenem orMeropenem ) (seeClin Infect DIs 5988 2014 ) OR
bull Uncontrolled small studies suggest potential benefit form the combination ofPolymyxinB +Minocycline200 mg loading dose then 100 mg q12h IV(see Comment for references)
bull No benefit from combination of Colistin + Rifampin vs Colistin alone (Clin Inf Dis 57 349 2013)
bull Colistin + Tigecycline (with Acinetobacter MIC
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
ndash For critically ill patient with polymyxin-resistantA baumanniibull Usually concomitant resistance to all beta-lactams aminoglycosides and
fluoroquinolones
bull Can try a polymyxin (for its detergent effect) plus a carbapenem
bull Clinical experience and editorial comment Clin Infect Dis 601295 amp 1304 2015 Lowest mortality observed with a combination of colistin + a carbapenem + ampicillin-sulbactam
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
bull What would be the drug of choice
bull How to dose with his renal function
bull How long to treat
How to prevent
Take Home Points
Questions
Thank You
How to prevent
Take Home Points
Questions
Thank You
Take Home Points
Questions
Thank You
Questions
Thank You
Thank You