Resistenze batteriche e terapia delle infezioni

postoperatorie

Resistenze batteriche e terapia delle infezioni

postoperatorie

Fausto de Lalla,VicenzaFausto de Lalla,Vicenza

Postoperative infection 2006Postoperative infection 2006

Despite the great advances Despite the great advances in surgical technique and in surgical technique and antibiotic prophylaxis, and antibiotic prophylaxis, and ongoing research in this ongoing research in this field, field, wound infection wound infection remains a considerable remains a considerable cause of morbidity and cause of morbidity and mortality among mortality among surgical patientssurgical patients

Antibiotic Resistance Antibiotic Resistance

The knowledge of The knowledge of sensitivity sensitivity patterns patterns of the most likely etiological agents of of the most likely etiological agents of postoperative infections is postoperative infections is pivotalpivotal for for the success of both the success of both

- - perioperative prophylaxisperioperative prophylaxis, and , and

- empiric - empiric treatmenttreatment of SSIs of SSIs

TRADITIONAL CLASSIFICATION TRADITIONAL CLASSIFICATION

Clean surgery Clean surgery Clean-contaminated surgeryClean-contaminated surgeryContaminated surgery Contaminated surgery Dirty surgeryDirty surgery

Pathogens Causing Surgical Site Infections Pathogens Causing Surgical Site Infections

Are different,Are different, in respect to the in respect to the surgical proceduresurgical procedure and the site and the site of infection. of infection.

Infections following: Infections following:

- - CLEAN SURGICAL PROCEDURESCLEAN SURGICAL PROCEDURES

(with or without implantation of vascular grafts (with or without implantation of vascular grafts or prosthetic devices)or prosthetic devices)

- - SUPERFICIAL,INCISIONAL SSIsSUPERFICIAL,INCISIONAL SSIs (i.e. simple (i.e. simple infection of the surgical incision, involving only infection of the surgical incision, involving only skin and subcutaneous tissue) :skin and subcutaneous tissue) :

are most often caused by are most often caused by

Staph. aureusStaph. aureus or or coag. negative coag. negative staphylococcistaphylococci

(patient’s skin flora, surgical team, exogenous environment)(patient’s skin flora, surgical team, exogenous environment)

Pathogens Causing Surgical Site Infections

Pathogens Causing Surgical Site Infections

Deep and “organ space” Deep and “organ space” infections followinginfections following

CLEAN- CONTAMINATED SURGERY :CLEAN- CONTAMINATED SURGERY :

- are more often - are more often polymicrobial polymicrobial infectionsinfections

- are caused by the normal - are caused by the normal endogenous microflora endogenous microflora of the of the structure which has been transectedstructure which has been transected

Most Likely SSI Pathogens according to Operation Type

Most Likely SSI Pathogens according to Operation Type

Operation Likely pathogensOperation Likely pathogens Appendectomy - gram-negativi bacilli + Appendectomy - gram-negativi bacilli +

anaerobesanaerobes

colorectal (B.fragilis)colorectal (B.fragilis) Gastroduodenal - gram-negativi bacilli Gastroduodenal - gram-negativi bacilli

oropharingeal oropharingeal

anarobes; streptococcianarobes; streptococci Biliary tract - gram-negativi Biliary tract - gram-negativi

bacilli±Enterococcus sppbacilli±Enterococcus spp OB/GYN. OB/GYN. - - gram-negativi bacilli + anaerobes gram-negativi bacilli + anaerobes

(B.(B.

fragilis)± enterococcus spp; fragilis)± enterococcus spp; streptococcstreptococc

Urologic - gram-negative bacilliUrologic - gram-negative bacilli Head and neckHead and neck - - oropharingeal anarobes ± gram-oropharingeal anarobes ± gram-

negative bacilli; streptococci;negative bacilli; streptococci;

Eziologia delle infezioni postoperatorieEziologia delle infezioni postoperatorie -ResistenzeResistenze -gram positivi-gram positivi - gram - gram negativi negativi - microrganismi in situazioni microrganismi in situazioni particolari particolari

Emerging Gram-positive Micro-organisms in Postoperative Infections

Emerging Gram-positive Micro-organisms in Postoperative Infections

MR staphylococciMR staphylococci

VR enterococci VR enterococci

Surgical Infection with Antibiotic-resistant Microorganisms

Surgical Infection with Antibiotic-resistant Microorganisms

Surgical patientsSurgical patients with with infections infections by by

MR staphylococci MR staphylococci or or VRE VRE have:have: a significantly higher mortality ratea significantly higher mortality rate

longer hospitalizationlonger hospitalization

longer treatment before the dischargelonger treatment before the discharge

than patients with infections by MS staphylococci or than patients with infections by MS staphylococci or glycopeptide sensitive enterococci glycopeptide sensitive enterococci

Nichols RL, Am J Med 1998;Nichols RL, Am J Med 1998; Gleason et al, Arch Surg 1999; Gleason et al, Arch Surg 1999;

Mekontso DA, et al. CID 2001; Mekontso DA, et al. CID 2001; Edmond MB, et al. CID 1996 Edmond MB, et al. CID 1996

Significance of Enterococci in Surgical Infections

Significance of Enterococci in Surgical Infections

Enterococcal bacteremia carries a serious Enterococcal bacteremia carries a serious prognosisprognosis

Patients with intra-abdominal infection and Patients with intra-abdominal infection and an initial isolation of enterococci have a an initial isolation of enterococci have a significant higher treatment failure rate *significant higher treatment failure rate *

VRE infections, and particularly VRE bacteremia, VRE infections, and particularly VRE bacteremia, are associated with high morbidity and are associated with high morbidity and mortality**mortality**

* Burnett RJ, Dellinger EP, et al. Surgery 1995* Burnett RJ, Dellinger EP, et al. Surgery 1995

** Edmond MB, et al. CID 1996** Edmond MB, et al. CID 1996

Microbiologia delle peritoniti secondaria(comunitaria) e postoperatoria (ospedaliera)

Microbiologia delle peritoniti secondaria(comunitaria) e postoperatoria (ospedaliera)

microrganismo comunitaria (%) ospedaliera(%) p microrganismo comunitaria (%) ospedaliera(%) p

- Enterococchi 5 Enterococchi 5 21 21 0,0010,001

- E. coli 36E. coli 36 19 19 0,0050,005

- Enterobacter spp. 3 12 Enterobacter spp. 3 12 0,05 0,05- Bacteroides spp 10Bacteroides spp 10 7 7 NS NS- Klebsiella spp 7 7Klebsiella spp 7 7 NS NS- S.aureus 1S.aureus 1 6 6 0,05 0,05- S.coagulasi neg. 1 5 S.coagulasi neg. 1 5 0,05 0,05- Streptococcus spp 14 4 Streptococcus spp 14 4 0,005 0,005- Pseudomonas spp 2 6 NSPseudomonas spp 2 6 NS

- Roehrborn A. CID 2001;33:1513-9Roehrborn A. CID 2001;33:1513-9

VRE: isolamenti per materialeVRE: isolamenti per materialeANNOANNO MATERIALEMATERIALE N° ISOLAMENTIN° ISOLAMENTI

20012001 FeciFeci 2424

Urine Urine 77

Ferita chir.Ferita chir. 33SangueSangue 22LiquorLiquor 11

Drenaggio Drenaggio bil.bil.

11

20022002 FeciFeci 8585

UrineUrine 33

Piaga decubitoPiaga decubito

BileBile11

11

MR Staphylococci in Surgical Site Infections (S.Bortolo Hospital)

MR Staphylococci in Surgical Site Infections (S.Bortolo Hospital)

Dept. S.aureus Coag. Neg. staph.Dept. S.aureus Coag. Neg. staph. MR/ tot S.aureus (%) MR/ tot. CNS (%)MR/ tot S.aureus (%) MR/ tot. CNS (%)

- Neurosurg. 35/39 (89.7) 18/26 (69.2)- Neurosurg. 35/39 (89.7) 18/26 (69.2)

- - Cardiosurg. 11/18 (61.1) 11/15 (73.3)Cardiosurg. 11/18 (61.1) 11/15 (73.3)

- Orthoped. 32/58 (55.2) 12/18 (66.7)- Orthoped. 32/58 (55.2) 12/18 (66.7)

TOTAL 78/115 (67.8) 41/59 (69.5)TOTAL 78/115 (67.8) 41/59 (69.5)de Lalla F. J Hosp Infect 2002de Lalla F. J Hosp Infect 2002

MR Staphylococci in Surgical Site Infections in Italy

MR Staphylococci in Surgical Site Infections in Italy

Ancona and Pesaro Hospitals (676 patients) *Ancona and Pesaro Hospitals (676 patients) *

- MR S. aureus/total S.aureus = 104/191 - MR S. aureus/total S.aureus = 104/191 (54%)(54%)

- MR CNS/total CNS = 71/138 - MR CNS/total CNS = 71/138 (51%)(51%) S.Bortolo Hospital,Vicenza **S.Bortolo Hospital,Vicenza **

-- MR S. aureus/total S.aureusMR S. aureus/total S.aureus = 78/115 (67.8%) = 78/115 (67.8%)

-- MR CNS/total CNS =MR CNS/total CNS = 41/59 (69.5) 41/59 (69.5)

86 orthopedic centers (2,013 isolates from86 orthopedic centers (2,013 isolates from

SSIs following TH or TK arthroplasties) ***SSIs following TH or TK arthroplasties) ***

-- MR S. aureus/total S.aureus = 212/463 MR S. aureus/total S.aureus = 212/463 (46%)(46%)

- MR CNS/total CNS = 156/304 - MR CNS/total CNS = 156/304 (51%)(51%)* Giacometti A et al. J Clin Microbiol 2000; de Lalla et al,J Hosp * Giacometti A et al. J Clin Microbiol 2000; de Lalla et al,J Hosp

Infect 2002;*** Mini E et al, J Chemother 2001Infect 2002;*** Mini E et al, J Chemother 2001

Implications of Resistance for Selection of Antibiotics in Surgery (1)

Implications of Resistance for Selection of Antibiotics in Surgery (1)

TREATMENTTREATMENT OF ESTABLISHED OF ESTABLISHED

INFECTIONS:INFECTIONS:1) SSIs following clean surgery1) SSIs following clean surgery::

- the high frequency of MR staphylococci as- the high frequency of MR staphylococci as

causative agents should be kept in mind, causative agents should be kept in mind,

AND AND

-- glycopetides should be administered glycopetides should be administered in the in the empiricempiric treatment of the treatment of the most most seriousserious of these infections (e.g. of these infections (e.g. prosthetic infections)prosthetic infections)

PERIOPERATIVE PROPHYLAXISPERIOPERATIVE PROPHYLAXIS::

- - The administration of The administration of glycopeptides as glycopeptides as prophylactic agents in clean prosthetic major prophylactic agents in clean prosthetic major

surgerysurgery is suggested by some Authors is suggested by some Authors ( (at at least for those least for those cardiovascularcardiovascular and and orthopedicorthopedic Depts. in which the Depts. in which the prevalence of MR staphylococci is prevalence of MR staphylococci is considerably highconsiderably high))

- - prophylactic glycopeptides are extensively prophylactic glycopeptides are extensively used in clinical practiceused in clinical practice

If the proportion of postoperative If the proportion of postoperative S. S. aureus iaureus infection caused by MRSA (in nfection caused by MRSA (in major vascular and orthopedic surgical major vascular and orthopedic surgical prostheses) were to rise to 20%, we prostheses) were to rise to 20%, we would probably advise using would probably advise using vancomycin or teicoplanin as vancomycin or teicoplanin as prophylactic agents in both of these prophylactic agents in both of these areasareas..

Adam P Fraise, J Antimicrob Chemother 1998; Adam P Fraise, J Antimicrob Chemother 1998; 42:287-28942:287-289

Antibiotic of choice in clean surgery prophylaxis

Antibiotic of choice in clean surgery prophylaxis

Vancomycin may be the agent of choice in Vancomycin may be the agent of choice in

certain clinical circumstancescertain clinical circumstances,such as a ,such as a

cluster of MRSA mediastinitis or incision cluster of MRSA mediastinitis or incision

infection due to MR coag.neg staphylococci. infection due to MR coag.neg staphylococci.

A threshold has not been scientifically A threshold has not been scientifically

defined that can support the decision to use defined that can support the decision to use

vancomycin. The decision should involve vancomycin. The decision should involve

local considerationslocal considerations..

CDC GuidelinesCDC Guidelines

Clinical consequences and cost of limiting use of vancomycin for perioperative prophylaxis:example of

coronary artery bypass surgery (CABS) *

Clinical consequences and cost of limiting use of vancomycin for perioperative prophylaxis:example of

coronary artery bypass surgery (CABS) *- -to compare clinical results and cost-effectiveness -to compare clinical results and cost-effectiveness

of no prophylaxis, cefazolin and vancomycin in of no prophylaxis, cefazolin and vancomycin in CABSCABS

- -Decision-analytic models -Decision-analytic models - -Vancomycin resulted in 7% fewer surgical -Vancomycin resulted in 7% fewer surgical

infections and 1% lower all-cause mortality and infections and 1% lower all-cause mortality and saved $ 117 per procedure,compared with saved $ 117 per procedure,compared with cefazolin.cefazolin.

- -Cefazolin resulted in substantially fewer -Cefazolin resulted in substantially fewer infections and deaths and lower costs than no infections and deaths and lower costs than no prophylaxisprophylaxis

- -Data on vancomycin’s impact on resistance are -Data on vancomycin’s impact on resistance are needed to quantify……..the future long term-needed to quantify……..the future long term-consequences to society consequences to society

- * Zanetti,Goldie, Platt, Emerg Infect Dis 2001;820-* Zanetti,Goldie, Platt, Emerg Infect Dis 2001;820-77

Glycopeptides Are No More Effective than ß-Lactam Agents for Prevention of Surgical Site Infection after Cardiac

Surgery: a Meta-analysis (Bolon et al,CID 2004)

Glycopeptides Are No More Effective than ß-Lactam Agents for Prevention of Surgical Site Infection after Cardiac

Surgery: a Meta-analysis (Bolon et al,CID 2004) 7 trials published between 1988-2002 on 5,761 subjects7 trials published between 1988-2002 on 5,761 subjects Glycopeptide : vancomycin (4 studies) or teicoplanin (3 trials)Glycopeptide : vancomycin (4 studies) or teicoplanin (3 trials) Comparators: cefazolin (3),cefuroxime (1),ceftriaxone Comparators: cefazolin (3),cefuroxime (1),ceftriaxone

(1),fluc+tobra (1)(1),fluc+tobra (1)

Prevalence of MRSAPrevalence of MRSA: low (6 trials), high (1 : low (6 trials), high (1 study)study)

Blinded: No (5 trials), yes (2studies)Blinded: No (5 trials), yes (2studies)

RESULTS : RESULTS : neither agent proved to be superiorneither agent proved to be superior for for prevention of occurrence of SSIprevention of occurrence of SSI (primary outcome (primary outcome at 30 at 30 days !!days !!))

In subanalyses:In subanalyses:

- - ß-lactams were superior to glycopeptides for prevention of ß-lactams were superior to glycopeptides for prevention of chest SSIs, andchest SSIs, and

- glycopetides were superior for prevention of - glycopetides were superior for prevention of SSIs caused by SSIs caused by MR gram + bacteriaMR gram + bacteria..

Implications of Resistance for Selection of Antibiotics in Surgery (2)

Implications of Resistance for Selection of Antibiotics in Surgery (2)

during treatment with 3rd gen cephalosporinsduring treatment with 3rd gen cephalosporins

enterococcal superinfection can occursenterococcal superinfection can occurs

the use of 3rd gen ceph.s is an the use of 3rd gen ceph.s is an important risk factor important risk factor for VREfor VRE colonization and infection in surgical patients colonization and infection in surgical patients * *

in the hospitals with high rates of VRE,in the hospitals with high rates of VRE, limitation limitation of of 3rd gen ceph.s use, with 3rd gen ceph.s use, with an increasean increase of penicillins of penicillins --LI LI combinationscombinations, is followed by a significant, is followed by a significant decrease decrease in the VRE infection ** in the VRE infection **

Dahms RA et al, Arch Surg 1998; ** May AK, Shock 2000 Dahms RA et al, Arch Surg 1998; ** May AK, Shock 2000

Implications of Resistance for Selection of Antibiotics in Surgery (3)

Implications of Resistance for Selection of Antibiotics in Surgery (3)

- The particular role of Enterococcus spp. as an - The particular role of Enterococcus spp. as an etiological agent of tertiary peritonitis (hospital etiological agent of tertiary peritonitis (hospital acquired peritonitis) should be kept in mind (acquired peritonitis) should be kept in mind (use of use of extended spectrum penicillins and penicillin- extended spectrum penicillins and penicillin- LIs LIs combinations in the treatment of abdominal and combinations in the treatment of abdominal and pelvic surgical infectionspelvic surgical infections) )

- Postoperative infections in patients who have been - Postoperative infections in patients who have been hospitalized for a prolonged period prior to surgery, hospitalized for a prolonged period prior to surgery, and/or have received prior antibiotic treatment are and/or have received prior antibiotic treatment are more likely to involve antibiotic resistant Gram more likely to involve antibiotic resistant Gram negative bacilli(ESBL producing negative bacilli(ESBL producing Klebsiella Klebsiella pneumoniae, E.coli, C.freundi, E.cloacae, S. pneumoniae, E.coli, C.freundi, E.cloacae, S. marcescens …..marcescens …..).: ).: the possible administration of the possible administration of carbapenems should be kept in mind carbapenems should be kept in mind