pierluigi viale clinica di malattie infettive università degli studi di udine

Università degli Studi di Udine – Clinica di Malattie Infettive

Pierluigi Viale

Clinica di Malattie Infettive

Università degli Studi di Udine

Pierluigi Viale

Clinica di Malattie Infettive

Università degli Studi di Udine

2° Infectivology today

Paestum 18-20 maggio 2006

2° Infectivology today

Paestum 18-20 maggio 2006

Etiopatogenesi e profilassi dell’infezione post-operatoriaEtiopatogenesi e profilassi

dell’infezione post-operatoria


Infected Uninfected

Mortality 7.8% 3.5%

ICU Adm 29% 18%

LOS 11d 6d

Re-admission 41% 7%

Impact of SSI’s


Prevention of SSI’s

Perioperative antimicrobial prevention measures

Maintain normal blood sugar levels

Hyper-oxygenation

Maintain normal body temperature

Hair removal immediately prior to operation using electric clippers

Hand washing

Good surgical technique

Control of host-related risk factors

Antibiotics


NRC Wound Classification

•Clean Surgical Procedures

atb prophylaxis not indicated *

•Clean Contimated Procedures

prophylaxis indicated

•Contaminated Procedures

therapy indicated

•Dirty Procedures

therapy indicated

* Two well recognized ATB indications for such clean operations are:

1. Any intravascular prosthetic material or prosthetic joint will be inserted

2. Any operation in which an incisional or organ space SSI would pose catastrophic risk

Cardiac surgeryNeurosurgical OperationsProsthetic arterial graftsRevascularization of lower extremity


Surgical Antimicrobial Prophylaxis

Surgical AMP refers to a very brief course of an antimicrobial agent initiated just before an operation begins. AMP is not an attempt to sterilize tissues, but a critically timed adjunct used to reduce the microbial burden of intra-operative contamination to a level that cannot overwhelm host defenses.


THE EQUATION OF THE INFECTIOUS RISK

BACTERIAL LOAD x VIRULENCE

HOST IMMUNITY

= INFECTIOUS RISK

+ DRUG RESISTANCE

HOST IMMUNITY

= INFECTIOUS RISK

Every Operation is an Experiment in Bacteriology …

+ ANTIBIOTICS


THE FIVE MAIN TOPIC OF SURGICAL ANTIBIOTIC PROPHYAXIS

• INDICATION

• TIMING OF ADMINISTRATION

• TIME OF ADMINISTRATION (single vs multiple dose)

• DRUG CHOICE

• DRUG DOSAGE

INDICATION


Antibiotic prophylaxis in orthopedics. An epidemiological survey in Italy

J Chemother 2000; 12 (supppl 2):28-38

136,312 procedures

24.4% arthroscopy

57.1% prophylaxis


Surgical site infection after groin hernia repairBritish J Surgery 2004; 91: 105–111

Site: Scotland

Sample : 2665 pts

Follow up: 30 days

Method: on call

n. Infections : 140

Infection rate: 5.3 %

ATB prophylaxis: 4.2%

NO prophylaxis 7.6%P = 0·002

Risk factors for wound infection : multivariate analysis


The role of antibiotic prophylaxis on wound infection after mesh hernia repair under local anesthesia on an ambulatory basis Hernia 2004;8:20-2

Randomized choice : CEFAZOLIN single dose (50 pts)

vs

PLACEBO (49 pts)

Infection rates : CEFAZOLIN 0

PLACEBO 8.1%P = .059


A prospective randomized trial of prophylactic antibiotics in elective laparoscopic cholecystectomy Surg Endosc 2003; 17:1716-8

Randomized choice : CEFOTAXIME 2 g single dose (49 pts)

vs

PLACEBO (43 pts)

Follow up: 30 days

Infection rates : CEFOTAXIME 2.04%

PLACEBO 2.32%


PIPERACILLIN TO PREVENT CHOLANGITIS AFTER ERCP.

A RANDOMIZED, CONTROLLED TRIAL Ann Intern Med 1996; 125:442-7

PIPERACILLIN (single dose) vs PLACEBO

551 consecutive pts enrolled

atb placebo

ACUTE CHOLANGITIS RATE 6% 4.4%

RR 0.73

(95% CI 0.36-1.51)


Biliary tract infections: a guide to drug treatment

Drugs 1999; 57: 81-91

“ antibacterial prophylaxis before ERCP should be reserved for patients with obstructive jaundice, since the risk of infectious complications seems to be strongly associated with this clinical condition…

… failure to achieve a full biliary drainage is the most important factor predicting bacteremia, and antimicrobial treatment should be prolonged until the bile duct is obstructed”


Antibiotic Prophylaxis After Endoscopic Therapy Prevents Rebleeding in Acute Variceal Hemorrhage: A Randomized Trial Hepatology 2004;39:746–753

Actuarial probability of remaining free of rebleeding

P .0029



• INDICATION



• DRUG CHOICE

• DRUG DOSAGE

CINETICA di CRESCITA BATTERICA CINETICA di CRESCITA BATTERICA

dopo CONTAMINAZIONE INTRA-OPERATORIAdopo CONTAMINAZIONE INTRA-OPERATORIA

Popolazione battericaPopolazione battericaUFC/mLUFC/mL

PROCEDURA CHIRURGICAPROCEDURA CHIRURGICA

TEMPOTEMPO

2 -6 ore2 -6 ore 3 -5 giorni3 -5 giorni

contaminazionecontaminazione

colonizzazionecolonizzazione

INFEZIONEINFEZIONE

BASI TEORICHE della PROFILASSI CHIRURGICABASI TEORICHE della PROFILASSI CHIRURGICA

Popolazione batterica e concentrazione dell’antibiotico in siero, trombi, ematomi e Popolazione batterica e concentrazione dell’antibiotico in siero, trombi, ematomi e coaguli coaguli

ANTIBIOTICO ANTIBIOTICO (mg/L)(mg/L)

UFC/mLUFC/mL

SOMMINISTRAZIONE SOMMINISTRAZIONE ANTIBIOTICOANTIBIOTICO

TEMPOTEMPO

MICMIC

Pop. BattericaPop. Battericaconc. Sieriche dell’antibioticoconc. Sieriche dell’antibioticoconc. dell’antib. in trombi, ematomi, conc. dell’antib. in trombi, ematomi, coagulicoaguli


Periodo vulnerabile

TIMING

Troppo precoce Timing corretto Troppo tardiva

100

10

1

Incisione cutanea

MIC

Siero

Interstizio tessuti

C>MICper tuttol’intervento


TIMING INCIDENCE OF INFECTIONS

• > 2 h pre-incision 3,8%

•< 2 h pre-incision 0,6%

•< 3 h post-incision 1,5%

•> 3 h post-incision 3,3%

The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. Classen DC et Al, N Classen DC et Al, N

Engl J Med 1992Engl J Med 1992

ANTIBIOTICO ANTIBIOTICO (mg/L)(mg/L)

UFC/mLUFC/mLTEMPOTEMPO

MICMIC

Pop. BattericaPop. Battericaconc. Sieriche dell’antibioticoconc. Sieriche dell’antibioticoconc. dell’antib. in trombi, ematomi, conc. dell’antib. in trombi, ematomi, coagulicoaguli


1^ SOMMINISTRAZIONE 1^ SOMMINISTRAZIONE ANTIBIOTICOANTIBIOTICO

2^ SOMMINISTRAZIONE 2^ SOMMINISTRAZIONE ANTIBIOTICOANTIBIOTICO

UFC/mLUFC/mL

BASI TEORICHE della PROFILASSI CHIRURGICABASI TEORICHE della PROFILASSI CHIRURGICA

Intraoperative Redosing of Cefazolin and Risk for Surgical Site Infection in Cardiac Surgery Zanetti et al, Emerging Infectious Diseases 2001

Antibiotico % legame pr. t1/2

eliminazione

Dose

intraop.

dopo ore

Cefazolina 70-85 1.4-1.5 3.5

Cefamandolo 65-85 0.6-0.8 1.5

Cefuroxima 33-50 1-2 3.5

Cefoxitina 70 0.7-1 1.5

Clindamicina 92-94 2-3 3.5

Gentamicina 5 2-3 3.5

Amoxic./ac. Clav 18-25 1-1.5 2.5

Ampic./sulbactam 15-25 1-15 2.5

FARMACOCINETICA DEGLI ANTIBIOTICI IMPIEGATI IN PROFILASSI CHIRURGICA



• INDICATION



• DRUG CHOICE

• DRUG DOSAGE


Ideal Prophylactic Agent

Excellent in vitro activity vs Staphylococci and Streptococci

Relatively long serum half-life

Good tissue penetration

Relatively non-toxic and well handling

Inexpensive

With low ability to collateral damage (selective pressure)


SURGICAL-SITE INFECTION RATES AND RISK FACTOR ANALYSIS IN CORONARY ARTERY BYPASS GRAFT SURGERY

Infect Control Hosp Epidemiol 2004;25:472-476

4,474 patients undergoing CABG surgery

aggregate SSI rate : 7.8 infections per 100 procedures ( CI 95 7.0–8.5)

56%56%

5

18

8

1313

S. aureus

CoNS

Enterobacteriaceae

No growth

Mixed flora


Intranasal Mupirocin to prevent post-operative S. aureus infections

Perl et al, N Engl J Med, 2002

Randomized, double-blind, placebo controlled trial

3864 patients included in the ITT analysis (891 S. aureus carriers)

2,3

4

2,4

7,7

overall S. aureus carriers

Mupirocin

Placebo

p = .002

S. aureus colonization and disease

Base-case analysis: clinical outcomes and costs for a hypothetical cohort of 10,000 patients undergoing coronary artery bypass graft surgery

Zanetti et al, Emerging Infectious Diseases 2001

Clinical, microbiological, and economic benefit of a change in antibiotic prophylaxis for cardiac surgery. Spelman D et al, Infect Control

Hosp Epidemiol 2002;23:402

10.5(95% CI 8.2-13.3)

4.9(95% CI 3.2-7.1)

CEF VANCO+RIFA

infe

cti

on

s p

er

10

0 p

roced

ure

s

An estimated $576,655 (Australian) was saved between two 12-month periods

from CEFAZOLIN to … VANCOMYCIN + RIFAMPICIN


Summary of the risk of surgical site infection (SSI) after receipt of glycopeptide or b-lactam prophylaxis for the outcome of SSIs

Glycopeptides Are No More Effective than b-Lactam Agents for Prevention of Surgical Site Infection after Cardiac Surgery: A Meta-analysis

Clin Infect Dis 2004; 38:1357–63

cefazolin

Glycopeptide



• INDICATION



• DRUG CHOICE

• DRUG DOSAGE


Type of study: prospective two-arms

Goal: assessing plasma exposure to teicoplanin with two different prophylactic regimens [Group A (n = 23), 800 mg pre-operatively vs Group B (n = 24), 400 mg pre-operatively plus two doses of 200 mg 24 h apart)]

Setting: patients undergoing major vascular surgery.

Pts N: 47

Pharmacokinetic-pharmacodynamic aspects of antimicrobial prophylaxis withteicoplanin in patients undergoing major vascular surgeryPea F, Furlanut M, Stellini R, Signorini L,Pavan F, Giulini SM, Viale P, Carosi G, Int J Antimicrob Ag, 2005

Clinic of Infectious Diseases & Institute of Clinical Pharmacology – University of Udine

2

Teic

op

lan

in c

on

cen

trati

on

(m

g/L

)

2

3

45678

20

30

1

10

Time of wound closure (h)

3 4 5 6 7 8 9

r = 0.56

400 mg

r = 0.32

800 mg

Pharmacokinetic-pharmacodynamic aspects of antimicrobial prophylaxis withteicoplanin in patients undergoing major vascular surgeryPea F, Furlanut M, Stellini R, Signorini L,Pavan F, Giulini SM, Viale P, Carosi G, Int J Antimicrob Ag, 2005

pierluigi viale clinica di malattie infettive università degli studi di udine

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