pierluigi viale clinica di malattie infettive università degli studi di udine
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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. Impact of SSI’s. Prevention of SSI’s. Perioperative antimicrobial prevention measures - PowerPoint PPT PresentationTRANSCRIPT
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
Università degli Studi di Udine – Clinica di Malattie Infettive
Infected Uninfected
Mortality 7.8% 3.5%
ICU Adm 29% 18%
LOS 11d 6d
Re-admission 41% 7%
Impact of SSI’s
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
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
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
BACTERIAL LOAD x VIRULENCE
HOST IMMUNITY
= INFECTIOUS RISK
+ DRUG RESISTANCE
HOST IMMUNITY
= INFECTIOUS RISK
Every Operation is an Experiment in Bacteriology …
+ ANTIBIOTICS
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
INDICATION
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 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
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 placebo
ACUTE CHOLANGITIS RATE 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
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
PROCEDURA CHIRURGICAPROCEDURA CHIRURGICA
Periodo vulnerabile
TIMING
Troppo precoce Timing corretto Troppo tardiva
100
10
1
Incisione cutanea
MIC
Siero
Interstizio tessuti
C>MICper tuttol’intervento
Università degli Studi di Udine – Clinica di Malattie Infettive
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
PROCEDURA CHIRURGICAPROCEDURA CHIRURGICA
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
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
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)
56%56%
5
18
8
1313
S. aureus
CoNS
Enterobacteriaceae
No growth
Mixed flora
Università degli Studi di Udine – Clinica di Malattie Infettive
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
Università degli Studi di Udine – Clinica di Malattie Infettive
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
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
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