antimicrobials use in cancer patients
DESCRIPTION
Antimicrobials Use in Cancer PatientsTRANSCRIPT
7th Oncology review Course on April 24-25, 2013 in Intercontinental Hotel, Jeddah
Mansoor Ahmed KhanB.Pharm, MS, BCOP
Clinical Pharmacist Adult Oncology/HemKAMC-WR Jeddah
Bugs and Drugs: Antimicrobials use in Cancer Patients
Do Bugs need Drugs in immunocompromized Cancer
patients
Introduction. Classification of Bacteria Normal Bacterial Flora MDRs Classification of Antibiotics Most common bugs and Abx Options Common infections in Oncology patients Febrile Neutropenia
Outlines
Gram-positive bacteria retain the stain, and hence appear purple or blue-black when visualised by bright-field microscopy.
Gram-negative bacteria cannot retain the dye complex, and need to be counterstained with a red dye such as carbol fuchsin before they can be seen in the bright-field microscope.
The shape of bacteria is also used to classify them. Bacteria display three basic shapes: round (cocci, from the Greek kokkos - a berry), rod shaped (bacilli, from the Latin bacillus - a stick or rod), or spiral.
Bases of Bacterial Classification
Gram Positive Cocci1. Staphyllococci (Clusters)2. Streptococci (Chains)3. Pneumococci Gram Positive Bacilli1. The genus bacillus2. Clostridia3. Other Gram Positive Bacilli- Listeria,
Corynebacterium
Classification of the Bacteria
GPC in Cluster: Staph
GPC in Chains: Streptococci
VRE
Gram Negative Cocci 1. Neisseria Gram Negative Bacilli1. Enterobacteriaceae- Major Class2. Pseudomonads3. Curved Gram Negative Rods4. Cocco-bacilli5. Other Gram Negative Bacilli- Legionella
Classification of the Bacteria
E.Coli
Pseudomonas Aeruginosa
Staphyllococci1. MSSA, MRSA2. MSSE- Coagulase Negative Staph, MRSE3. VRSA, VRSE Streptococci1. Non-Hemolytic Streptococci (Enterococci,
E.fecalis VSE, VRE)2. Hemolytic Streptococci
α-hemolytic streptococci (S.pneumonia, S.viridans) β-hemolytic streptococci (Group A, B,C,D, G)
(S.pyogenes)
Gram Positive Cocci
Bacillus (spore forming)B.anthracis (Anthrax), B.cereus
ClostridiaC.Difficile (diarrhea), C.perfringes (gangrene), C.botulinum (Botulism)
Other Gram Positive Bacilli Listeria (Meningitis), Corynebacterium (Diphtheria), Propionibacterium acne
Gram Positive Bacilli
Neisseria (Diplococci)
Neisseria meningitidis is an important cause of bacterial meningitis
Neisseria gonorrhoeae causes gonorrhoea.
Gram Negative Cocci
Gram Negative Bacilli
Enterobacteriaceae1. E.Coli2. Klebsiella3. Salmonella4. Shigella5. Proteus6. Yersinia7. Citrobacter8. Enterobacter9. Morganella10. providentia
PseudomonadsP.Aeruginosa
Curved GN- Rods Vibrio Campylobacter H.Pylori
Contd Gram Negative Bacilli
Cocco-bacilli Moraxella Acinetobacter Haemophilus
H.Influenza H.Parainfluenza
Others Legionella Bordetella Bartonella Stenotrophomonas
Obligatory GN Anaerobes
1. Bacteroids
Anaerobes
Gram +ve Anaerobes
Gram Positive Cocci1. Peptococcus Spp2. Peptostreptococcus Spp Endospore forming GPB1. Clostridium Non-spore forming GPB1. Actinomyces Spp2. Eubacterium3. Propionibacterium
Gram -ve Anaerobes Gram negative Bacilli1. Bacteroides fragilis2. Other Bacteroides Spp3. Fusobacterium
Gram Negative Cocci1. Neisseria meningitidis2. Neisseria gonorrhoeae3. Veillonella
Miscellaneous
Chlamydia 1. C.trachomatis (STD)2. C.pneumonia (Live Stock)3. C.psittaci (Birds)
Riscketsia1. R.prowazekii2. R.ricketsii
Spirochaetes (STD)1. Treponema pallidum
(Syphilis)
2. T. pallidum pertenue (Yaws)
Mycoplasma Pneumonia
AFB1. MAC2. M.kansasii3. M.leprae4. M.tuberculosis
Normal Bacterial Flora
Skin Staphylococci and Corynebacterium
Conjunctiva Sparse, GPC and GNB
Oral Cavity Streptococci and Lactobacillus
Nasal Staphylococci and Corynebacterium
Pharynx Strept, Neisseria, GNB and GNC
Stomach H.Pylori (Upto 50%)
Normal Bacterial Flora
Small Intestine
Lactics, Enterics, Enterococci
Colon Bacteroides, Lactics, Enterics, Enterococci, Clostridia
Ant Urethera Sparse, Staphylococci, Corynebacterium, Enterics
Vagina Lactic during child bearing age otherwise mixed flora.
Multidrug Resistant pathogens
Gram +ve1. MRSA2. VRSA3. VISA4. MRSE5. VRE
Gram –Ve1. Pseudomonas2. Xanthomonas or
Stenotrophomonas3. Acinetobacter4. ESBL Inducers
(Klebsiella + E.Coli + 1-3 in KKH)
Classification Of Antibiotics
CW synthesis Inhibitor
1. Penicillins2. Cephalosporins3. Carbapenems4. Glycopeptide Folate Antagonist1. Sulfonamides
Protein synthesis Inhibitor
1. Tetracyclines2. Aminoglycosides3. Macrolides-Lincosamide4. Streptogramins5. Chloramphenicol DNA Gyrase Inhibitors1. Fluroquinolones
Penicillin
Penicillins Penicillin G Penicillin V Antistaphyllococcal Cloxacillin Flucloxacillin Methicillin Oxacillin Nafcillin
Extended Spectrum1. Amoxicillin2. Augmentin3. Ampicillin4. Unasyn Antipseudomonal1. Piperacillin2. Tazocin3. Ticarcillin4. Timentin
Strept, GPB, Anaerobes
Staph, Strept, H.pylori , E.Coli,
Klebsiella , Salmonella, Anaerobes
Enterobacteriaceae, PSEAER, Anaerobes,
Staph, Strept
Cephalosporins
1st Generation Cefazolin Cefalexin 2nd Generation Cefuroxime Cefprozil Cefaclor Cefonicid Cefoxitin Loracarbef Cefotetan
3rd Generation Cefotaxime Ceftriaxone Ceftazidime Cefpodoxime Cefixime 4th Generation Cefepime Cefoperazone 5th Generation Ceftaroline
MSSA, Strep, E.Coli, Proteus
Klebsiella, H.Infleunza, Moraxella, Morganella
MSSA, Strep, E.Coli,
Klebsiella, H.Infleunza,
Proteus
ACIBAU, Citrobacter, Enterobacter
, Serratia, Pseudomona
s, Salmonella
Gram +ve ,
Gram -ve, PSEAER
MSSA, MRSA, Gram –Ve but
no PSEAER coverage
Carbapenems Imipenem Meropenem Doripenem Ertapenem Biapenem PZ-601
Monobactams Aztreonam
Carbapenems & Monobactams
MSSA, Strept, ACIBAU, PSEAER, Citrobacter, Enterobacter, ESBLs,
Klebsiella, E.Coli, H.Infleunza, Proteus, Serratia, Anaerobes,
Same as Carbapenems but no
Gram Positive Coverage and no
ACIBAU
Vancomycin Teicoplanin
Glycopeptides
MSSA, MRSA, VSE, CNSTA, Streptococci, Diptheroids
Daptomycin
Lipopeptide
MSSA, MRSA, VSE, CNSTA, Streptococci, Diptheroids
Tetracycline OTC Demeclocycline Minocycline Doxycycline Tigecycline (Derivative of Minocycline and
broad spectrum. Covers G+ve and G-ve and MDR strains except PSEAER & Proteus)
Tetracyclines
ACIBAU, Anaerobes, Brucella,
Camplylobacter, Chlamydia,
Enterobacter, E.Coli, H.Influenza, Listeria,
Mycoplasma, Shigella, Strept, Yersinia, Vibrio
Streptomycin Amikacin Gentamycin Tobramycin Neomycin (PO or Topical) Kanamycin (PO or Topical)
Aminoglycosides
Enterobacteriaceae, PSEAER,
ACIBAU
Macrolides and Related Agents-MLS
Macrolides1. Erytheromycin2. Clarythromycin3. Azithromycin
Clindamycin
Streptogramins Quinopristin-
Dalfopristine (synercid) MRSA, VRE
Oxazoladinones Linezolid MRSA,
VRE
Staph, Strept,
Atypical, H.influen
za, Moraxella
Staph, Strept,
Anaerobes
Sulfonamides
Sulfonamides Sulfamethoxazole Sulfapyridine Sulfadiazine Sulfisoxazol Sulfamethizole
Pyrimidines Trimethoprim (TMP) Pyrimethamine Fixed Combinations1. Septrin (SMZ+ TMP)
2. Fansidar (Sulfadoxine+ Pyrimethamine) Malaria
PCP, Stenotrophomon
as, Enterobacteriace
ae
Fluroquinolones
1st Generation1. Nalidixic Acid2. Norfloxacin3. Cinoxacin 2nd Generation1. Ciprofloxacin2. Levofloxacin3. Ofloxacin4. Lomefloxacin5. Enoxacin
3rd Generation Gatifloxacin Sparfloxacin 4th Generation Moxifloxacin
MSSA, Strept Enterobacteriace
ae
MSSA, Strept Enterobacteriace
ae, Atypical, Anaerobes
PSEAER, Atypical
MSSA, Strept Enterobacteriace
ae, Atypical, Anaerobes
WEAK Gram -
ve & Weak Gram +ve
Antimycobacterial Drugs
1st Line ATT INH Rifampin PZA Ethambutol Streptomycin
2nd Line ATT Amikacin Capreomycin Moxifloxacin Ciprofloxacin Levofloxacin PAS Ethionamide Cycloserine
Bacteriostatic Vs Bactericidal
Bacteriostatic1. Sulfonamides2. Tetracyclines3. Chloramphenicol4. Linezolid (except
streptococci)
Bactericidal1. Penicillins2. Cephalopsorins3. Glycopeptides4. Carbapenems5. Aminoglycosides6. Macrolides7. Fluroquinolones8. Sulfonamide +TMP
Treatment Options against Various Bugs
MSSA- Cloxacillin, Augmentin
MRSA- Vancomycin
VSE-Vancomycin
VRE-Linezolid
Pseudomonas- Tazocin, Amikacin Carbapenem, Cefepime, Ciproflox
Stenotrophomonas- Septrin
Acinetobacter- Colistin, Carbapenems, Tigecyclin
ESBL Inducers-Carbapenem
Anaerobes, Flagyl, Clindamycin
Atypical Pneumonia-Zithromax
PCP- Septrin
Enterobacteriaceae- Cipro, Moxi, Penicillins, Cephalosporins, Amikacin, Gentamycin
Listeria, Ampicillin
Site Specific Infections in Oncology
Meningitis Endocarditis URTI LRTI UTI Skin and soft tissue Intraabdominal
Pseudomembranous Colitis
Otitis Media CAP HAP Febrile Neutropenia
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Definitions
Neutropenia: Absolute neutrophil count (ANC) < 500 cells/mm3 OR
expected to go <500 cells/mm3 during next 48hr
Profound Neutropenia: ANC <100 cells/mm3
Functional Neutropenia: impaired phagocytosis & killing of pathogens despite normal neutrophil count
Fever: Oral temperature measurement that is ≥ 38.30 C (1010 F) once ≥ 380 C (100.50 F) for > 1 hr
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Common organisms
A recent prospective observational study involved > 2000 pts showed that only 23% of FN episodes associated with bacteremia
G+ve 57% > G-ve 34% > polymicrobial 9%
Mortality associated bacteremia G-ve > G+ve 18% vs 5%
P. aeruginosa coverage remains an essential component of initial empirical Abx regimen
Klastersky J et al. Bacteraemia in febrile neutropeniccancer patients. Int J Antimicrob Agents 2007; 30(Suppl 1):S51–9.Pizzo PA, et al. Empiric antibiotic and antifunga ltherapy for cancer patients with prolonged fever and granulocytopenia. Am J Med 1982; 72:101–11.Schimpff SC. Empiric antibiotic therapy for granulocytopenic cancer patients. Am J Med 1986; 80:13–20.
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Mucositis- Common source of infection
www.pacificprosthodontics.com/.../ oncology.html
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Risk Assessment, MASCC Score
Burden of febrile neutropenia with no or mild symptoms
5
No hypotension (systolic blood pressure>90 mmHg) 5
No chronic obstructive pulmonary disease 4
Solid tumor or hematologic malignancy with no previous fungal infection
4
No dehydration requiring parenteral fluids 3
Burden of febrile neutropenia with moderate symptoms
3
Outpatient status 3
Age < 60 years 2
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Risk Assessment
High risk patient
Anticipated neutropenic period to last >7 days & profound neutropenia
Significant medical co-morbid condition
Should be hospitalized for empirical Abx.
MASCC score < 21
Anticipated neutropenic period to last ≤ 7 days
No or few comorbidities Candidate for oral &/or
outpatient empirical therapy
MASCC score ≥21
Low risk patient
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Empiric Antibiotic Therapy
Monotherapy Broad spectrum, anti pseudomonal antibiotics
Piperacillin /tazobactam : 4.5gm IV q6h Carbapenem Imipenem/cilastatin : 500mg IV q6h Meropenem : 1gm IV q8h : 2gm IV q8h
(meningitis) Cefepime : 2gm IV q8h Ceftazidime : 2gm IV q8h
Need dose adjustment in renal patient
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Empiric Antibiotic Therapy
For PCN allergic patient use either:
Ciprofloxacin + Clindamycin OR
Aztreonam + Vancomycin
Either combination will ensure anti pseudomonal and G +ve coverage.
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Saudi Arabia National Guard - Health Affair
King Khalid National Guard Hospital
INTERNAL POLICY AND PROCEDURE (IPP)
Saudi Arabia National Guard - Health AffairKing Khalid National Guard Hospital
Clinical pathway : Febrile Neutropenia in adults patients .
Responding
Discontinue therapy after 48hr of neutropil recovery
NeutropeniaNo neutropenia
Continue IV therapy for 7days then Ciprofloxacin 500 mg PO q12
hr and Augmentin 625 mg PO q8hr
for 7 days
ID Consultation for Type and duration of
therapy
Documented infection
Fever of unknown origin
Not Responding
Blood culturesCT chest
Abelcet 5 mg/kg q24ID Consultation
Stable Deteriorating
Continue Tazocin Discontinue Amikacin
Do not add Vancomycin
Imipenem 500mg IV q6hr
Vancomycin 15mg/kg IV q12hr
Thanks and Questions
END
Bugs & Drugs Antimicrobial Reference 2012
Alison G. Freifeld et al. Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Diseases Society of America. Clinical Infectious Diseases 2011;52(4):e56–e93
John’s Hopkins Antibiotics guide
References