Diapositiva 1

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2 Infectivology today Paestum 18-20 maggio 2006
Etiopatogenesi e profilassi dellinfezione
post-operatoria
Pierluigi Viale Clinica di Malattie
Infettive Università degli Studi di Udine
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What do SSIs give rise to?

• SSIs increase hospital stay by 7-10 days.
• SSIs increase hospital costs
• Deep SSIs longer hospital stay and cost
• SSIs increase readmission rates
• 40-60 SSIs preventable with appropriate
  behavior
• and correct use of antibiotics

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Impact of SSIs
Infected Uninfected
Mortality 7.8 3.5
ICU Adm 29 18
LOS 11d 6d
Re-admission 41 7
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Prevention of SSIs

• 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

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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 surgery Neurosurgi
cal Operations Prosthetic arterial
grafts Revascularization of lower extremity
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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.
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THE EQUATION OF THE INFECTIOUS RISK
BACTERIAL LOAD x VIRULENCE
INFECTIOUS RISK
INFECTIOUS RISK
HOST IMMUNITY
HOST IMMUNITY
ANTIBIOTICS
Every Operation is an Experiment in Bacteriology
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THE FIVE MAIN TOPIC OF SURGICAL ANTIBIOTIC
PROPHYAXIS
INDICATION

• INDICATION
• TIMING OF ADMINISTRATION
• TIME OF ADMINISTRATION (single vs multiple dose)
• DRUG CHOICE
• DRUG DOSAGE

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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
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Surgical site infection after groin hernia repair
British J Surgery 2004 91 105111
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 0002
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The role of antibiotic prophylaxis on wound
infection after mesh hernia repair under local
anesthesia on an ambulatory basis Hernia
2004820-2
Randomized choice CEFAZOLIN single dose (50
pts) vs PLACEBO (49 pts) Infection
rates CEFAZOLIN 0 PLACEBO 8.1
P .059
12
A prospective randomized trial of prophylactic
antibiotics in elective laparoscopic
cholecystectomy Surg Endosc 2003
171716-8
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
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PIPERACILLIN TO PREVENT CHOLANGITIS AFTER
ERCP. A RANDOMIZED, CONTROLLED TRIAL Ann Intern
Med 1996 125442-7
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)
14
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
15
Antibiotic Prophylaxis After Endoscopic Therapy
Prevents Rebleeding in Acute Variceal Hemorrhage
A Randomized Trial Hepatology 200439746753
Actuarial probability of remaining free of
rebleeding
P .0029
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THE FIVE MAIN TOPIC OF SURGICAL ANTIBIOTIC
PROPHYAXIS

• INDICATION
• TIMING OF ADMINISTRATION
• TIME OF ADMINISTRATION (single vs multiple dose)
• DRUG CHOICE
• DRUG DOSAGE

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CINETICA di CRESCITA BATTERICA dopo
CONTAMINAZIONE INTRA-OPERATORIA
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BASI TEORICHE della PROFILASSI CHIRURGICA
Popolazione batterica e concentrazione
dellantibiotico in siero, trombi, ematomi e
coaguli
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TIMING
Incisione cutanea
100
Siero
Interstizio tessuti
10
CgtMIC per tutto lintervento
Periodo vulnerabile
MIC
1
Troppo precoce
Timing corretto
Troppo tardiva
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The timing of prophylactic administration of
antibiotics and the risk of surgical-wound
infection. Classen DC et Al, N Engl J Med 1992
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BASI TEORICHE della PROFILASSI CHIRURGICA
ANTIBIOTICO (mg/L)
Pop. Batterica conc. Sieriche dellantibiotico con
c. dellantib. in trombi, ematomi, coaguli
PROCEDURA CHIRURGICA
MIC
UFC/mL
UFC/mL
TEMPO
1 SOMMINISTRAZIONE ANTIBIOTICO
2 SOMMINISTRAZIONE ANTIBIOTICO
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Intraoperative Redosing of Cefazolin and Risk
for Surgical Site Infection in Cardiac Surgery
Zanetti et al, Emerging Infectious Diseases 2001
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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
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THE FIVE MAIN TOPIC OF SURGICAL ANTIBIOTIC
PROPHYAXIS

• INDICATION
• TIMING OF ADMINISTRATION
• TIME OF ADMINISTRATION (single vs multiple dose)
• DRUG CHOICE
• DRUG DOSAGE

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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)

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SURGICAL-SITE INFECTION RATES AND RISK FACTOR
ANALYSIS IN CORONARY ARTERY BYPASS GRAFT
SURGERY Infect Control Hosp Epidemiol
200425472-476
4,474 patients undergoing CABG surgery aggregate
SSI rate 7.8 infections per 100 procedures (
CI 95 7.08.5)
Mixed flora
13
No growth
8
56
S. aureus
18
Enterobacteriaceae
5
CoNS
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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
Placebo
2,4
2,3
overall
S. aureus carriers
28
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
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Clinical, microbiological, and economic
benefit of a change in antibiotic prophylaxis
for cardiac surgery. Spelman D et al, Infect
Control Hosp Epidemiol 200223402
from CEFAZOLIN to VANCOMYCIN RIFAMPICIN
10.5 (95 CI 8.2-13.3)
4.9 (95 CI 3.2-7.1)
infections per 100 procedures
CEF
VANCORIFA
An estimated 576,655 (Australian) was saved
between two 12-month periods
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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 38135763
Summary of the risk of surgical site infection
(SSI) after receipt of glycopeptide or b-lactam
prophylaxis for the outcome of SSIs
cefazolin
Glycopeptide
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THE FIVE MAIN TOPIC OF SURGICAL ANTIBIOTIC
PROPHYAXIS

• INDICATION
• TIMING OF ADMINISTRATION
• TIME OF ADMINISTRATION (single vs multiple dose)
• DRUG CHOICE
• DRUG DOSAGE

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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
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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
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20
10
r 0.32
8
7
6
5
Teicoplanin concentration (mg/L)
4
3
r 0.56
2
1
2
3
4
5
6
7
8
9
Time of wound closure (h)