How to use antimicrobial prophylaxis

Nagoya City University Hospital Infection Control Team

Takehiro WAKASUGI M.D., Ph. D.

 SSI management

It is important to prevent SSI

Preoperative Intraoperative Postoperative

DM control AMP Wound management
smoking Room circumstance surveillance
MRSA Sterilized cloths etc.
Hair remove Operation procedures
etc. etc.

It is important to deal with perioperative

management by all medical employees as
Bundle
Antimicrobial prophylaxis (AMP)
 Four principles for antimicrobial prophylaxis

(1) Use an AMP agent for all operations or classes of operations in which
its use has been shown to reduce SSI rates based on evidence from
clinical trials
(2) Use an AMP agent that is safe, inexpensive, and bactericidal with an in
vitro spectrum that covers the most probable intraoperative
contaminants for the operation.
(3) Time the infusion of the initial dose of antimicrobial agent so that a
bactericidal concentration of the drug is established in serum and
tissues by the time the skin is incised.
(4) Maintain therapeutic levels of the antimicrobial agent in both serum
and tissues throughout the operation and until, at most, a few hours
after the incision is closed in the operating.

Mangram AJ, et al; Infect control Hosp Epidemiol, 20, 247-78, 1999
 AMP prevents SSI of clean-contaminated surgery
Gastrointestinal surgery
Wound Infection(%) Wound
Infection(%)
Drug Authors Routes Drug Control P Drug Authors Routes Drug Control P
Cephaloridine Polk and Lopez-Mayor IM 0 31 <.05 Cephaloridine Polk and Lopez-Mayor IM 7 30 <.05
Evans and Pollock IM/IV 3 20 <.05 Evans and Pollock IM/IV 29 43 NS
Lewis et al IV 0 26 <.05 Hughes et al IM 15 38 <.05
Stone et al IM/IV 5 9 NS
Stone et al IM/IV 4 0 NS
(compared with cefamandole)
(compared with
Lewis et al IM/IV 10 6 NS
cefamandole)
(compared with oral erythromycin,neomysin)

Cefazolin Stone et al IM 4 19 <.05 Cephradine Lewis et al IV 36 10 NS

Pories et al IV 4 22 NS (compared with oral metronidazole erythromycin)

Cefamandole Nichols et al IV 5 35 <.05 Cefamandole Stone et al IM/IV 9 4 NS

(compared with cefamandole)
Stone et al IM/IV 0 4 NS
Slama et al IV 33 31 NS
(compared with (compared with cefalothin)
cephaloridine) Eisenberg IV 4 6 NS
(compared with cefalothin)
Upper GI surgery Mehigan et al IV 6 3 NS
(compared with penicillin,gentamisin,clindamycin)

Cephalothin Kjellgren,Sellstrom IV 18 53 <.05

Slama et al IV 31 33 NS
(compared with cefamandole)
Eisenberg IV 6 4 NS
(compared with cefamandole)
Lindhagen et al IV 11 10 NS
(compared with fosfomycin)
Condon et al IV 39 6 <.05
(compared with erythromycin,neomycin)

Colorectal colorectal
Guglielmo B, et al ; Arch surg, 118, 943-55,1983
 Classification of surgery

(1)Clean surgery
no infected surgery (breast, hernia repair)
(2)Clean-contaminated surgery
usual surgery for gastrointestinal tract, genital tract,
urinary tract
(3)Contaminated surgery
(4)Dirty infected surgery
perforated organ surgery, surgery for abscess
AMP prevents SSI of clean surgery

Breast surgery Hernia repair

SSI

Clean-contaminated

Platt R, et al ; N Engl J Med, 32, 153-60,1990

 Target pathogens for prevention of SSI

Graft S. aureus, coagulase-negative staphylococci

Cardiac S. aureus, coagulase-negative staphylococci
Neurosurgery S. aureus, coagulase-negative staphylococci
Breast S. aureus, coagulase-negative staphylococci
Ophthalmic S. aureus, coagulase-negative staphylococci, streptococci, GNR
Orthopedic S. aureus, coagulase-negative staphylococci,GNR
Thoracic S. aureus, coagulase-negative staphylococci, S. pneumoniae, GNR
Vascular S. aureus, coagulase-negative staphylococci
Appendectomy GNR, anaerobes
Biliary tract GNR, anaerobes
Colorectal GNR, anaerobes
Gastroduodenal GNR, anaerobes, oropharyngeal anaerobes
Head and neck GNR, anaerobes, oropharyngeal anaerobes
Gynecologic GNR, enterococci, group B streptococci, anaerobes
Urologic GNR

Mangram AJ, et al; Infect control Hosp Epidemiol, 20, 247-78, 1999
 Timing of initial AMP infusion
It is the most effective to apply initial AMP 0-2 hours before incision.

Classen DC, et al ; N Engl J Med, 326, 281-6,1992

 Appropriate AMP adding timing
It is preferable to add AMP every 3 hours during operation.

MICs of cefazorin for main SSI pathogens Change in cefazorin concentrations

at tissues

MSSA MIC80=0.5g/gl Serum

K. Pneumonia MIC80=4.0g/gl Peritoneum
E. Coli MIC80=4.0g/gl Adipose tissue
Streptococcus spp MIC80=4.0g/gl Pancreatic tissue

Ohge H ,et al ; Jpn J Surg, 29,1233-6,1999

 Appropriate AMP duration
It is not preferable to continue AMP administration more than 48 hours after operation
% of Patients
Variable Total n With SSI (n) OR (95% CI) P
<48 1502 9 (131)
Duration of prophylaxis, h 1.0 (0.8-1.8) 0.9
>48 1139 9 (100)
Yes 2180 8 (184)
Prophylactic CEZ exposure 0.8 (0.6-1.1) 0.2
No 461 10 (47)
Yes 385 11 (41)
Prophylactic VCM exposure 1.3 (0.9-1.8) 0.2
No 2256 8 (190)
Yes 222 10 (23)
Prophylactic CTRX exposure 1.2 (0.8-1.9) 0.4
No 2419 9 (208)

Prolonged AMP administration increases the appearance of resistant pathogens

Patients With Positive Cultures
(n=426)
Variable OR P 95% CI
Prolonged prophylaxis (>48h) 1.6 0.027 1.1-2.6
Age >65y 1.3 0.022 1.0-1.6
Combined CABG/valve surgery 2.7 0.002 1.4-5.1
Antibiotic therapy after CABG 1.8 0.054 1.0-3.3
Harbarth S, et al; Circulation, 101, 2916-21, 2000
 Nagoya City Univ. Hospital Policy
Mannual of antimicrobial prophylaxis
 Retrospective survey
Appropriate use of AMP at NCU hospital
 Discussion
(1) Initial administration
3 hour adding
The necessity of anesthesiologists collaboration
Intraoperative AMP administration has been
routined
(2) Antibiotics choice
Postoperative administration duration
Decision of doctor-in-chief
Inadequate education for doctor
Postoperative administration duration tends to be
prolonged