2° Infectivology today
Paestum 18-20 maggio 2006
Etiopatogenesi e profilassi
dell’infezione post-operatoria
Pierluigi Viale
Clinica di Malattie Infettive
Università degli Studi di Udine
Università degli Studi di Udine – Clinica di Malattie Infettive
Impact of SSI’s
Infected
Uninfected
Mortality
7.8%
3.5%
ICU Adm
29%
18%
LOS
11d
6d
Re-admission
41%
7%
Università degli Studi di Udine – Clinica di Malattie Infettive
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
Università degli Studi di Udine – Clinica di Malattie Infettive
NRC Wound Classification
•Clean Surgical Procedures
 atbATB
prophylaxis
indicated
*
* Two well recognized
indications not
for such
clean operations
are:
•Clean Contimated Procedures
1. Any intravascular prosthetic material or prosthetic joint will be
inserted
 prophylaxis indicated
•Contaminated
Procedures
2. Any operation
in which an incisional or organ space SSI would
pose catastrophic
risk
 therapy
indicated
Cardiac surgery
•Dirty Procedures Neurosurgical Operations
Prosthetic
arterial grafts
 therapy
indicated
Revascularization of lower extremity
Università degli Studi di Udine – Clinica di Malattie Infettive
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.
Università degli Studi di Udine – Clinica di Malattie Infettive
THE EQUATION OF THE INFECTIOUS RISK
+ DRUG RESISTANCE
BACTERIAL LOAD x VIRULENCE
HOST IMMUNITY
HOST
= INFECTIOUS
RISK
= INFECTIOUS
RISK
IMMUNITY
+ ANTIBIOTICS
Every Operation is an Experiment in Bacteriology …
Università degli Studi di Udine – Clinica di Malattie Infettive
THE FIVE MAIN TOPIC OF SURGICAL ANTIBIOTIC PROPHYAXIS
• INDICATION
• TIMING OF ADMINISTRATION
• TIME OF ADMINISTRATION (single vs multiple dose)
• DRUG CHOICE
• DRUG DOSAGE
Università degli Studi di Udine – Clinica di Malattie Infettive
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
Università degli Studi di Udine – Clinica di Malattie Infettive
Surgical site infection after groin hernia repair
British 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
Università degli Studi di Udine – Clinica di Malattie Infettive
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
Università degli Studi di Udine – Clinica di Malattie Infettive
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%
Università degli Studi di Udine – Clinica di Malattie Infettive
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
ACUTE CHOLANGITIS RATE
placebo
6%
4.4%
RR 0.73
(95% CI 0.36-1.51)
Università degli Studi di Udine – Clinica di Malattie Infettive
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”
Università degli Studi di Udine – Clinica di Malattie Infettive
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
Università degli Studi di Udine – Clinica di Malattie Infettive
THE FIVE MAIN TOPIC OF SURGICAL ANTIBIOTIC PROPHYAXIS
• INDICATION
• TIMING OF ADMINISTRATION
• TIME OF ADMINISTRATION (single vs multiple dose)
• DRUG CHOICE
• DRUG DOSAGE
Università degli Studi di Udine – Clinica di Malattie Infettive
CINETICA di CRESCITA BATTERICA
dopo CONTAMINAZIONE INTRA-OPERATORIA
PROCEDURA CHIRURGICA
Popolazione batterica
UFC/mL
colonizzazione
INFEZIONE
contaminazione
TEMPO
2 -6 ore
3 -5 giorni
BASI TEORICHE della PROFILASSI CHIRURGICA
Popolazione batterica e concentrazione dell’antibiotico in siero, trombi, ematomi e coaguli
ANTIBIOTICO
(mg/L)
PROCEDURA CHIRURGICA
Pop. Batterica
conc. Sieriche dell’antibiotico
conc. dell’antib. in trombi, ematomi, coaguli
MIC
UFC/mL
SOMMINISTRAZIONE
ANTIBIOTICO
TEMPO
TIMING
100
Incisione cutanea
Siero
Interstizio tessuti
10
C>MIC
per tutto
l’intervento
Periodo
vulnerabile
MIC
1
Troppo precoce
Timing corretto
Troppo tardiva
The timing of prophylactic administration of antibiotics and the
risk of surgical-wound infection.
Classen DC et Al, N Engl J Med 1992
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%
Università degli Studi di Udine – Clinica di Malattie Infettive
BASI TEORICHE della PROFILASSI CHIRURGICA
ANTIBIOTICO
(mg/L)
Pop. Batterica
conc. Sieriche dell’antibiotico
conc. dell’antib. in trombi, ematomi, coaguli
PROCEDURA CHIRURGICA
MIC
UFC/mL
UFC/mL
1^ SOMMINISTRAZIONE
ANTIBIOTICO
2^ SOMMINISTRAZIONE
ANTIBIOTICO
TEMPO
Intraoperative Redosing of Cefazolin and Risk for Surgical Site
Infection in Cardiac Surgery Zanetti et al, Emerging Infectious Diseases 2001
FARMACOCINETICA DEGLI ANTIBIOTICI IMPIEGATI IN
PROFILASSI CHIRURGICA
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
THE FIVE MAIN TOPIC OF SURGICAL ANTIBIOTIC PROPHYAXIS
• INDICATION
• TIMING OF ADMINISTRATION
• TIME OF ADMINISTRATION (single vs multiple dose)
• DRUG CHOICE
• DRUG DOSAGE
Università degli Studi di Udine – Clinica di Malattie Infettive
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)
Università degli Studi di Udine – Clinica di Malattie Infettive
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)
Mixed flora
No growth
Enterobacteriaceae
13
8
56%
18
S. aureus
5
CoNS
Università degli Studi di Udine – Clinica di Malattie Infettive
S. aureus colonization and disease
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)
7,7
p = .002
Mupirocin
4
2,3
Placebo
2,4
overall
S. aureus carriers
Università degli Studi di Udine – Clinica di Malattie Infettive
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
infections per 100 procedures
from CEFAZOLIN to … VANCOMYCIN + RIFAMPICIN
10.5
(95% CI 8.2-13.3)
4.9
(95% CI 3.2-7.1)
CEF
VANCO+RIFA
An estimated $576,655 (Australian) was saved between two 12-month periods
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
Summary of the risk of surgical site infection (SSI) after receipt of
glycopeptide or b-lactam prophylaxis for the outcome of SSIs
cefazolin
Glycopeptide
Università degli Studi di Udine – Clinica di Malattie Infettive
THE FIVE MAIN TOPIC OF SURGICAL ANTIBIOTIC PROPHYAXIS
• INDICATION
• TIMING OF ADMINISTRATION
• TIME OF ADMINISTRATION (single vs multiple dose)
• DRUG CHOICE
• DRUG DOSAGE
Università degli Studi di Udine – Clinica di Malattie Infettive
Pharmacokinetic-pharmacodynamic aspects of antimicrobial prophylaxis with
teicoplanin in patients undergoing major vascular surgery
Pea F, Furlanut M, Stellini R, Signorini L,Pavan F, Giulini SM, Viale P, Carosi G, Int J Antimicrob Ag, 2005
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
Università degli Studi di Udine – Clinica di Malattie Infettive
Pharmacokinetic-pharmacodynamic aspects of antimicrobial prophylaxis with
teicoplanin in patients undergoing major vascular surgery
Pea F, Furlanut M, Stellini R, Signorini L,Pavan F, Giulini SM, Viale P, Carosi G, Int J Antimicrob Ag, 2005
Teicoplanin concentration (mg/L)
30
800 mg
400 mg
20
10
8
7
6
5
4
r = 0.32
3
r = 0.56
2
1
2
3
4
5
6
7
8
9
Time of wound closure (h)
Clinic of Infectious Diseases & Institute of Clinical Pharmacology – University of Udine