1、PERIOPERATIVE ANTIBIOTIC PROPHYLAXIS AND SURGICAL SITE INFECTION,Paul A. Kearney MD, FACS Professor of Surgery Chief, Section of Trauma and Critical Care University of Kentucky,You aint gonna learn what you dont want to know.,Grateful Dead,Department of Surgery 1964,Ben Eiseman - Chairman Frank C. S
2、pencer Benjamin Rush Rene Menguy Ward O. Griffen Tom Brower,Kentucky Dialect,Versailles,Vursales,Athens,Aythens,Louisville,Looavul,Irvine,Ervun,Liketakillme,Hurts like hell!,Aherdat!,Affirmation or Agreement,“Survival of the fittest”,Herbert Spencer,Antibiotics and Resistance,Close association betwe
3、en use of antibiotics and emergence of resistant pathogens Prior antibiotic exposure coupled with several other risk factors Prolonged LOS Presence of invasive devices,Kollef MH. Clin Infect Dis. 2000;31:S131-8,Factors Increasing Antibiotic Resistance,Increased severity of illness More severely immu
4、nocompromised patients Newer devices and procedures Resistance in the community Ineffective infection control and compliance Increased prophylactic, empiric antibiotics Higher antibiotic use per area per unit time,Epidemiology,18 million surgical procedures yearly 486,000 nosocomial infections 20% i
5、n intensive care unit, with SICU highest risk Patients have longer and costlier hospitalization Twice as likely to die Mortality rate up to 44% in ICU patients 60% more likely to spend time in ICU Five times more likely to be re-admitted Excess direct cost $5,038/infected patient,Kirkland KB, et al.
6、 Infect Control Hosp Epidem. 1999;20:725-30 Wallace WC et al. Amer Surg 1999;65:987-989,Emerging Pathogen,What is an emerging pathogen?,EMERGING INFECTIOUS DISEASES: DEFINITION,New, reemerging or drug-resistant infections whose incidence in humans has increased within the past two decades or whose i
7、ncidence threatens to increase in the near future,Institute of Medicine,What are the “Emerging Pathogens”?,Multi-Drug Resistant Gram Negative Bacilli ESBLs (E. coli, Klebsiella) P. aeruginosa Acinetobacter spp. Vancomycin-Resistant Enterococci Enterococcus faecium Methicillin-Resistant S. aureus Clo
8、stridium difficile-Associated Disease,Consequences of Overuse of Cephalosporins,*Extended Spectum Beta-Lactmases * Vancomycin Resistant Enterococci,Selection,Selection,Hyperproduced Bush Group I Chromosomal -Lactamases in Gram-Negative Bacteria,Originally were the chromosomal inducible enzymes in P.
9、 aeruginosa and enterobacteriaceae. Originally induced by ampicillin and cefoxitin With the introduction of cefotaxime and ceftazidime selection of strains with derepressed (hyperproduced) group 1 enzymes occurred. Confers resistance to most cephalosporins, monobactams, and penicillins, until recent
10、ly remained susceptible to carbapenems,Bush K. CID 2001; 32: 1085-9,Antibiotic doses ceftazidime,Production of -Lactamase,Loss of repressor gene (amp C gene),Hyperproduction of inducible enzyme,MIC = 4 mcg/ml,MIC = 16 mcg/ml,MIC = 64 mcg/ml,Question 1 Which IV Antibiotic(s) Would You Choose for Prop
11、hylaxis of Elective Colon Surgery?,A. Ampicillin/sulbactam B. Cefazolin C. Cefoxitin D. Ceftriaxone and metronidazole E. Gentamicin and metronidazole,Question 1 Which IV Antibiotic(s) Would You Choose for Prophylaxis of Elective Colon Surgery?,A. Ampicillin/sulbactam B. Cefazolin C. Cefoxitin D. Cef
12、triaxone and metronidazole E. Gentamicin and metronidazole,Panel Response Which Would You Choose for Prophylaxis of Elective Colon Surgery?,Question 2 When Would You Administer The First Dose of Antibiotic(s)?,A. At 10:30 AM B. “On call” to the OR C. In the preoperative holding area D. Upon inductio
13、n of anesthesia E. At the time of skin incision,Question 2 When Would You Administer The First Dose of Antibiotic(s)?,A. At 10:30 AM B. “On call” to the OR C. In the preoperative holding area D. Upon induction of anesthesia E. At the time of skin incision,Panel Response When Would You Administer The
14、 First Dose?,Question 3 When would you give the next dose of antibiotic(s)?,A. At 4-hour point B. At 6-hour point C. In Recovery Room D. None needed,Question 3 When would you give the next dose of antibiotic(s)?,A. At 4-hour point B. At 6-hour point C. In Recovery Room D. None needed,Panel Response
15、When would you give the next dose?,Major Pathogens in Surgical Wound Infection,NNIS 1990-1996,Appropriate Prophylactic AB infections mortality costs,Inappropriate Prophylactic AB adverse events likelihood resistant pathogens resistance globally,Appropriate Antibiotic Prophylaxis,Shortest duration of
16、 antibiotics with equivalent efficacyDosing at correct time intervalNarrowest spectrum with equivalent efficacyUse of an antibiotic with good safety profile,Appropriate Antibiotic Prophylaxis,Shortest duration of antibiotics with equivalent efficacyDosing at correct time intervalNarrowest spectrum w
17、ith equivalent efficacyUse of an antibiotic with good safety profile,Duration of Therapy,Period: 10/1/95 and 4/30/97 Data from charts collected and retrospectively reviewed End points of study: Frequency prophylaxis continued 24 h Cost of prophylaxis given 1 d Frequency of line infections and bacter
18、emias in patients receiving 4 days of prophylaxis,Namias N, et al J Am Coll Surg 1999;188:225-230,Effect of Duration on Infections,Namias N, et al J Am Coll Surg 1999;188:225-230,Appropriate Antibiotic Prophylaxis,Shortest duration of antibiotics with equivalent efficacyDosing at correct time interv
19、alNarrowest spectrum with equivalent efficacyUse of an antibiotic with good safety profile,Timing and Risk of Wound Infection,Prospective study 2847 patients Elective clean or “clean-contaminated” surgery Timing of prophylaxis Early- 2 to 24 hrs pre-operatively Preoperatively- 2 h before the incisio
20、n Perioperative- 3 h after incision Postoperative- 3 and24 h after incision,Classen DC, et al. NEJM 1992;326:281-285,Temporal Relation Between Prophylaxis and Infection,*See definitions As denoted by logistic-regression analysis P0.0001 as compared to preoperative group P=0.001 P=0.12 as compared to
21、 preoperative group | P=0.23 # P=0.0001,Relation Between Timing and Surgical Wound Rate,Classen DC, et al. NEJM 1992;326:281-285,Timeliness of Antibiotic Prophylaxis,Retrospective review of charts Abdominal aortic aneurysm repair Partial or total hip replacement Large bowel resection 44 teaching hos
22、pitals in New York State 2256 Medicare patients 395 Medicaid patients,Silver A, et al. Am J Surg 1996;171(6):548-52,Abx Delivery in Relation to Time,Timeliness of Antibiotic Prophylaxis,44 different Abx utilized 86% of patients received Abx 63% received timely antibiotics 26% received antibiotics ea
23、rly 10% received intra-operatively 1% received late Prophylaxis performed in 81% to 94% of cases 27% to 54% of all cases did not receive in a timely fashion Recommends delegating administration of prophylaxis to anesthesia team,Silver A, et al. Am J Surg 1996;171(6):548-52,Timeliness of Antibiotic P
24、rophylaxis,44 different Abx utilized 14% received no antibiotics 37% of those Rxed received at inappropriate time Recommend delegating prophylaxis to anesthesia team,Silver A, et al. Am J Surg 1996;171(6):548-52,UNIVERSITY OF KENTUCKY HOSPITAL Cardiovascular Surgery Pre-op Antibiotic Usage July 2000
25、 - September 2001,Timing of Administration,Prophylactic antibioticsInduction of anesthesiaRe-dose antibiotics if procedures 4 hrsmajor blood loss during procedure,Appropriate Antibiotic Prophylaxis,Shortest duration of antibiotics with equivalent efficacyDosing at correct time intervalNarrowest spec
26、trum with equivalent efficacyUse of an antibiotic with good safety profile,EMERGENCE OF MRSA,Fukatsu K, et al. Arch Surg. 1997;132:1320-1325,TYPES OF PROPHYLAXIS PROVIDED OVER TIME,Fukatsu K, et al. Arch Surg. 1997;132:1320-1325,* P0.01 vs. Index Period (1982-1984),TIMING OF PROPHYLAXIS,*,Fukatsu K,
27、 et al. Arch Surg. 1997;132:1320-1325,* P0.01 vs. Index Period (1982-1984),Results of Interventions,Fukatsu K, et al. Arch Surg. 1997;132:1320-1325,RATES OF POSTOPERATIVE INFECTION,*,*=P0.01 vs. Index period,Fukatsu K, et al. Arch Surg. 1997;132:1320-1325,RESULTS,Overuse of 3rd-generation cephalospo
28、rins for extended periods caused an MRSA outbreak Long-term prophylaxis did not lower infection rates MRSA rates decreased as usage of third-generation cephalosporins declined Prophylaxis with first- or second-generation cephalosporins should be as brief as possible,Fukatsu K, et al. Arch Surg. 1997
29、;132:1320-1325,Appropriate Antibiotic Prophylaxis,Shortest duration of antibiotics with equivalent efficacyDosing at correct time intervalNarrowest spectrum with equivalent efficacyUse of an antibiotic with good safety profile,Safety Issues,Antibiotic use and adverse drug events (ADEs) 4031 tertiary
30、 care center admissions for ADEs and potential ADEs Antibiotics second most common drug class for ADEs ADEs in 24% of those receiving antibiotics,Bates DW, et al JAMA 1995; 274: 29-34,INDICATIONS FOR ANTIBIOTICS,Jobe BA., et al. Am J Surg 1995;169:480-3,Potential Role of Prophylaxis,(N=103),Priviter
31、a G, et al. Antimicrob Agents Chemother. 1991;35(1):208-10,RESULTS,Most frequent indicators of CDAD Abdominal pain Distention Nausea Fever White blood cells and presence or absence of blood in stool did not contribute to diagnosis,Jobe BA., et al. Am J Surg 1995;169:480-3,INCIDENCE OF CDAD,Jobe BA.,
32、 et al. Am J Surg 1995;169:480-3,RESULTS,Strong positive correlation with 3rd-generation cephalosporins Strong negative correlation for ticarcillin/clavulanate, aminoglycosides, and metronidazole Increased association with IV vancomycin but not statistical No correlation for 1st- or 2nd-generation c
33、ephalosporins or erythromycin,Anand A.,et al. Am J Gastroenter 1994:4:519-23,RESULTS,Mean age at diagnosis 52 yrs. 55% of cases were surgical patients 20% were immunocompromised Post-organ transplant AIDs Oncology patients on myelosuppressive chemotherapy 97% had diarrhea,Jobe BA., et al. Am J Surg
34、1995;169:480-3,RESULTS,Overall mortality 3.5% Majority of patients developing CDAD (64%) received multiple antibiotics Cephalosporin usage, alone or in combination, associated with CDAD Ampicillin/sulbactam associated with CDAD Ticarcillin/clavulanic acid not associated with development of CDAD,Jobe
35、 BA., et al. Am J Surg 1995;169:480-3,Antibiotic Utilization in Surgical Patients with C. difficile-associated Diarrhea,Ciprofloxacin and cefoxitin most common antibiotics prescribed before diagnosis Patients with C. difficile had higher mortality compared with control (31% vs. 11% (p = 0.01) Time f
36、rom completion of antibiotic course to diagnosis was 7 +/- 2 days 16 % developed diarrhea after prophylactic antibiotics,Crabtree et al Amer Surgery 1999; 65: 507-12.,PROBLEM,CDAD currently principal cause of diarrhea in the hospital Incidence of CDAD increasing Broad-spectrum antibiotics alter norm
37、al aerobic/anaerobic balance Reduced “colonization resistance” Third-generation cephalosporins implicated Cefotaxime Ceftriaxone,Settle CD, et al. Aliment Pharmacol 12:1217-1223,RESULTS,P=0.001,P=0.006,Percent,Settle CD, et al. Aliment Pharmacol 12:1217-1223,ASSOCIATION OF SELECTED ANTIMICROBIAL WIT
38、H CDAD,+ Common + Uncommon - Rare,When Should Antibiotic Prophylaxis Be Used?,Surgical procedures with a high rate of wound infections clean-contaminated, contaminated Implantation of prosthetic materials Surgical procedures where infection would have severe consequences,Type of Procedure Risk of SS
39、IClean 30%,Nichols RL - Amer J Surg 1996; 172: 68-74,Traditional Classification of Operative Procedures and Risk of Infection,* Dirty wounds infection - antibiotics indicated as therapy,Medical Conditions Known to Increase Risk of Surgical Site Infection,extremes of age undernutrition obesity diabet
40、es prior site irradiation,hypoxemia remote infection corticosteroid therapy recent operation chronic inflammation,Antibiotic prophylaxis may be indicated in clean cases when associated conditions increase infection risk,NNIS Risk Index as a Predictor of Risk of Infection,Nichols RL, Martone WJ. Surg
41、ery 2000; 128: S2-S13,Technical Factors May Outweigh Benefit,Fluid/blood collections Ischemia/poor blood supply Inoculum,Clean Surgical Procedures,Most do not require antibioitcs Indicated in Prosthetic materials Cardiothoracic, vascular procedures Possibly breast and hernia Likely pathogens Above w
42、aist Gram positive aerobic coverage - cefazolin Below waist Gram positive and Gram negative enterics - cefazolin,Platt R et al . NEJM 1990; 322:153-60,Clean Surgical Procedures,Special Circumstances Increased risk of MRSA known colonization with MRSA hospital MRSA infection rate at 50% ?chronic dial
43、ysis, chronic diabetic foot ulcersVancomycin alone - above the waist Vancomycin alone - below waist,Clean Contaminated/ Contaminated Procedures,Head and Neck cefazolin + metronidazole clindamycin + gentamicinGastroduodenal cefazolin - high risk onlyBiliary tract cefazolin - high risk only ?2GC or Am
44、p/sul laparoscopic - none,Appendectomy (non-perf) Ampicillin/sulbactamColorectal oral prep neomycin + eryth. Ampicillin/sulbactam + combination in high riskGynecologic cefazolin or Ampicillin/sulbactam,Appropriate Duration of Therapy,Single dose therapy is as effective as multiple doses in majority
45、of studiesLonger therapy indicated in some cases usually related to inadequate dataNo studies indicate prophylaxis longer than 72 hrs is beneficialNo studies support continuing therapy for drains/tubes,Appropriate Duration of Therapy,Neurosurgical Recommendation: single dose meta-analysis found no d
46、ifference in single vs multiple dose regimensHead and Neck Recommendation: 24 hours single dose/ 24 hours not studied,Am J Health Syst Pharm 1999; 56:1839-88,Appropriate Duration of Therapy,Cardiothoracic Recommendation: 72 hours studies demonstrate no difference in single, short, or longer courses
47、of therapy. No evidence to support continued coverage of mediastinal drainsGastroduodenal Recommendation: single dose 2 studies demonstrate equal efficacy with multiple dose,Am J Health Syst Pharm 1999; 56:1839-88,Appropriate Duration of Therapy,Hepatobiliary Recommendation: single dose multiple stu
48、dies demonstrate equal efficacy with single and multiple doseAppendectomy Recommendation: single dose studies with single dose or multiple dose regimens demonstrate similar infection ratesColorectal Recommendation: single dose multiple studies single vs multiple dose, only 2 with same regimen - no d
49、ifference in infection rates,Appropriate Duration of Therapy,Vascular Recommendation: 24 hours inadequate studies examining 24 hoursSolid Organ Transplant Insufficient studies for heart and liver Recommendations: Heart: 48 - 72 hours Liver: 48 hours Kidney: single dose,Am J Health Syst Pharm 1999; 56:1839-88,Prophylactic Antibiotics Appropriate Choice,Narrowest spectrum to cover likely pathogens Avoid agents that are therapeutic choices3rd/4th generation cephalosporins and new agents should not be used Agents with moderately long half-life Good safety profile,
