Evaluating the optimal timing of surgical antimicrobial prophylaxis: study protocol for a randomized controlled trial

Edin Mujagic, Tibor Zwimpfer, Walter R Marti, Marcel Zwahlen, Henry Hoffmann, Christoph Kindler, Christoph Fux, Heidi Misteli, Lukas Iselin, Andrea Kopp Lugli, Christian A Nebiker, Urs von Holzen, Fabrizio Vinzens, Marco von Strauss, Stefan Reck, Marko Kraljević, Andreas F Widmer, Daniel Oertli, Rachel Rosenthal, Walter P Weber, Edin Mujagic, Tibor Zwimpfer, Walter R Marti, Marcel Zwahlen, Henry Hoffmann, Christoph Kindler, Christoph Fux, Heidi Misteli, Lukas Iselin, Andrea Kopp Lugli, Christian A Nebiker, Urs von Holzen, Fabrizio Vinzens, Marco von Strauss, Stefan Reck, Marko Kraljević, Andreas F Widmer, Daniel Oertli, Rachel Rosenthal, Walter P Weber

Abstract

Background: Surgical site infections are the most common hospital-acquired infections among surgical patients. The administration of surgical antimicrobial prophylaxis reduces the risk of surgical site infections . The optimal timing of this procedure is still a matter of debate. While most studies suggest that it should be given as close to the incision time as possible, others conclude that this may be too late for optimal prevention of surgical site infections. A large observational study suggests that surgical antimicrobial prophylaxis should be administered 74 to 30 minutes before surgery. The aim of this article is to report the design and protocol of a randomized controlled trial investigating the optimal timing of surgical antimicrobial prophylaxis.

Methods/design: In this bi-center randomized controlled trial conducted at two tertiary referral centers in Switzerland, we plan to include 5,000 patients undergoing general, oncologic, vascular and orthopedic trauma procedures. Patients are randomized in a 1:1 ratio into two groups: one receiving surgical antimicrobial prophylaxis in the anesthesia room (75 to 30 minutes before incision) and the other receiving surgical antimicrobial prophylaxis in the operating room (less than 30 minutes before incision). We expect a significantly lower rate of surgical site infections with surgical antimicrobial prophylaxis administered more than 30 minutes before the scheduled incision. The primary outcome is the occurrence of surgical site infections during a 30-day follow-up period (one year with an implant in place). When assuming a 5% surgical site infection risk with administration of surgical antimicrobial prophylaxis in the operating room, the planned sample size has an 80% power to detect a relative risk reduction for surgical site infections of 33% when administering surgical antimicrobial prophylaxis in the anesthesia room (with a two-sided type I error of 5%). We expect the study to be completed within three years.

Discussion: The results of this randomized controlled trial will have an important impact on current international guidelines for infection control strategies in the hospital. Moreover, the results of this randomized controlled trial are of significant interest for patient safety and healthcare economics.

Trial registration: This trial is registered on ClinicalTrials.gov under the identifier NCT01790529.

Figures

Figure 1
Figure 1
Study flow chart. CDC: Centers for Disease Control and Prevention; SAP: surgical antimicrobial prophylaxis.

References

    1. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection, 1999. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol. 1999;20:250–278. doi: 10.1086/501620. quiz 279–280.
    1. Coello R, Charlett A, Wilson J, Ward V, Pearson A, Borriello P. Adverse impact of surgical site infections in English hospitals. J Hosp Infect. 2005;60(2):93–103. doi: 10.1016/j.jhin.2004.10.019.
    1. Coskun D, Aytac J, Aydinli A, Bayer A. Mortality rate, length of stay and extra cost of sternal surgical site infections following coronary artery bypass grafting in a private medical centre in Turkey. J Hosp Infect. 2005;60(2):176–179. doi: 10.1016/j.jhin.2004.10.017.
    1. Kirkland KB, Briggs JP, Trivette SL, Wilkinson WE, Sexton DJ. The impact of surgical-site infections in the 1990s: attributable mortality, excess length of hospitalization, and extra costs. Infect Control Hosp Epidemiol. 1999;20(11):725–730. doi: 10.1086/501572.
    1. Jenney AW, Harrington GA, Russo PL, Spelman DW. Cost of surgical site infections following coronary artery bypass surgery. ANZ J Surg. 2001;71(11):662–664. doi: 10.1046/j.1445-1433.2001.02225.x.
    1. McGarry SA, Engemann JJ, Schmader K, Sexton DJ, Kaye KS. Surgical-site infection due to Staphylococcus aureus among elderly patients: mortality, duration of hospitalization, and cost. Infect Control Hosp Epidemiol. 2004;25(6):461–467. doi: 10.1086/502422.
    1. Ortona L, Federico G, Fantoni M, Pallavicini F, Ricci F, Antinori A. A study on the incidence of postoperative infections and surgical sepsis in a university hospital. Infect Control. 1987;8(8):320–324.
    1. Vegas AA, Jodra VM, Garcia ML. Nosocomial infection in surgery wards: a controlled study of increased duration of hospital stays and direct cost of hospitalization. Eur J Epidemiol. 1993;9(5):504–510.
    1. Engemann JJ, Carmeli Y, Cosgrove SE, Fowler VG, Bronstein MZ, Trivette SL, Briggs JP, Sexton DJ, Kaye KS. Adverse clinical and economic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection. Clin Infect Dis. 2003;36(5):592–598. doi: 10.1086/367653.
    1. Hollenbeak CS, Murphy DM, Koenig S, Woodward RS, Dunagan WC, Fraser VJ. The clinical and economic impact of deep chest surgical site infections following coronary artery bypass graft surgery. Chest. 2000;118(2):397–402. doi: 10.1378/chest.118.2.397.
    1. Poulsen KB, Bremmelgaard A, Sorensen AI, Raahave D, Petersen JV. Estimated costs of postoperative wound infections. A case-control study of marginal hospital and social security costs. Epidemiol Infect. 1994;113(2):283–295. doi: 10.1017/S0950268800051712.
    1. Whitehouse JD, Friedman ND, Kirkland KB, Richardson WJ, Sexton DJ. The impact of surgical-site infections following orthopedic surgery at a community hospital and a university hospital: adverse quality of life, excess length of stay, and extra cost. Infect Control Hosp Epidemiol. 2002;23(4):183–189. doi: 10.1086/502033.
    1. Yasunaga H, Ide H, Imamura T, Ohe K. Accuracy of economic studies on surgical site infection. J Hosp Infect. 2007;65(2):102–107. doi: 10.1016/j.jhin.2006.07.008.
    1. World Health Organization. Safe Surgery Saves Lives: WHO Guidelines for Safe Surgery 2009. Geneva: WHO; 2009. Objective 6: The team will consistently use methods known to minimize the risk for surgical site infection.
    1. Dellinger EP, Gross PA, Barrett TL, Krause PJ, Martone WJ, McGowan JE Jr, Sweet RL, Wenzel RP. Quality standard for antimicrobial prophylaxis in surgical procedures. Infectious Diseases Society of America. Clin Infect Dis. 1994;18(3):422–427. doi: 10.1093/clinids/18.3.422.
    1. Page CP, Bohnen JM, Fletcher JR, McManus AT, Solomkin JS, Wittmann DH. Antimicrobial prophylaxis for surgical wounds. Guidelines for clinical care. Arch Surg. 1993;128(1):79–88. doi: 10.1001/archsurg.1993.01420130087014.
    1. Clarke JS, Condon RE, Bartlett JG, Gorbach SL, Nichols RL, Ochi S. Preoperative oral antibiotics reduce septic complications of colon operations: results of prospective, randomized, double-blind clinical study. Ann Surg. 1977;186(3):251–259. doi: 10.1097/00000658-197709000-00003.
    1. Nygaard K, Hognestad J. Infection prophylaxis with doxycycline in colorectal surgery. A preliminary report. Scand J Gastroenterol Suppl. 1980;59:37–39.
    1. Baum ML, Anish DS, Chalmers TC, Sacks HS, Smith H Jr, Fagerstrom RM. A survey of clinical trials of antibiotic prophylaxis in colon surgery: evidence against further use of no-treatment controls. N Engl J Med. 1981;305(14):795–799. doi: 10.1056/NEJM198110013051404.
    1. Stone HH, Haney BB, Kolb LD, Geheber CE, Hooper CA. Prophylactic and preventive antibiotic therapy: timing, duration and economics. Ann Surg. 1979;189(6):691–699. doi: 10.1097/00000658-197906000-00004.
    1. Polk HC Jr, Lopez-Mayor JF. Postoperative wound infection: a prospective study of determinant factors and prevention. Surgery. 1969;66(1):97–103.
    1. Pories WJ, Van Rij AM, Burlingham BT, Fulghum RS, Meelheim D. Prophylactic cefazolin in gastric bypass surgery. Surgery. 1981;90(2):426–432.
    1. Chodak GW, Plaut ME. Use of systemic antibiotics for prophylaxis in surgery: a critical review. Arch Surg. 1977;112(3):326–334. doi: 10.1001/archsurg.1977.01370030098018.
    1. Kaiser AB, Clayson KR, Mulherin JL Jr, Roach AC, Allen TR, Edwards WH, Dale WA. Antibiotic prophylaxis in vascular surgery. Ann Surg. 1978;188(3):283–289. doi: 10.1097/00000658-197809000-00003.
    1. Hasselgren PO, Ivarsson L, Risberg B, Seeman T. Effects of prophylactic antibiotics in vascular surgery. A prospective, randomized, double-blind study. Ann Surg. 1984;200(1):86–92. doi: 10.1097/00000658-198407000-00016.
    1. Fong IW, Baker CB, McKee DC. The value of prophylactic antibiotics in aorta-coronary bypass operations: a double-blind randomized trial. J Thorac Cardiovasc Surg. 1979;78(6):908–913.
    1. Austin TW, Coles JC, Burnett R, Goldbach M. Aortocoronary bypass procedures and sternotomy infections: a study of antistaphylococcal prophylaxis. Can J Surg. 1980;23(5):483–485.
    1. Geraghty J, Feely M. Antibiotic prophylaxis in neurosurgery. A randomized controlled trial. J Neurosurg. 1984;60(4):724–726. doi: 10.3171/jns.1984.60.4.0724.
    1. Barker FG 2nd. Efficacy of prophylactic antibiotic therapy in spinal surgery: a meta-analysis. Neurosurgery. 2002;51(2):391–400. discussion 400–401.
    1. Lidwell OM, Lowbury EJ, Whyte W, Blowers R, Stanley SJ, Lowe D. Infection and sepsis after operations for total hip or knee-joint replacement: influence of ultraclean air, prophylactic antibiotics and other factors. J Hyg (Lond) 1984;93(3):505–529. doi: 10.1017/S0022172400065098.
    1. Bullock R, Van Dellen JR, Ketelbey W, Reinach SG. A double-blind placebo-controlled trial of perioperative prophylactic antibiotics for elective neurosurgery. J Neurosurg. 1988;69(5):687–691. doi: 10.3171/jns.1988.69.5.0687.
    1. Shapiro M, Wald U, Simchen E, Pomeranz S, Zagzag D, Michowiz SD, Samuel-Cahn E, Wax Y, Shuval R, Kahane Y. Randomized clinical trial of intra-operative antimicrobial prophylaxis of infection after neurosurgical procedures. J Hosp Infect. 1986;8(3):283–295. doi: 10.1016/0195-6701(86)90125-8.
    1. Young RF, Lawner PM. Perioperative antibiotic prophylaxis for prevention of postoperative neurosurgical infections. A randomized clinical trial. J Neurosurg. 1987;66(5):701–705. doi: 10.3171/jns.1987.66.5.0701.
    1. Platt R, Zucker JR, Zaleznik DF, Hopkins CC, Dellinger EP, Karchmer AW, Bryan CS, Burke JF, Wikler MA, Marino SK. Perioperative antibiotic prophylaxis and wound infection following breast surgery. J Antimicrob Chemother. 1993;31:43–48. doi: 10.1093/jac/31.suppl_B.43.
    1. Platt R, Zucker JR, Zaleznik DF, Hopkins CC, Dellinger EP, Karchmer AW, Bryan CS, Burke JF, Wikler MA, Marino SK. Prophylaxis against wound infection following herniorrhaphy or breast surgery. J Infect Dis. 1992;166(3):556–560. doi: 10.1093/infdis/166.3.556.
    1. Platt R, Zaleznik DF, Hopkins CC, Dellinger EP, Karchmer AW, Bryan CS, Burke JF, Wikler MA, Marino SK, Holbrook KF. Perioperative antibiotic prophylaxis for herniorrhaphy and breast surgery. N Engl J Med. 1990;322(3):153–160. doi: 10.1056/NEJM199001183220303.
    1. Lewis RT, Weigand FM, Mamazza J, Lloyd-Smith W, Tataryn D. Should antibiotic prophylaxis be used routinely in clean surgical procedures: a tentative yes. Surgery. 1995;118(4):742–746. doi: 10.1016/S0039-6060(05)80044-3. discussion 746–747.
    1. Yerdel MA, Akin EB, Dolalan S, Turkcapar AG, Pehlivan M, Gecim IE, Kuterdem E. Effect of single-dose prophylactic ampicillin and sulbactam on wound infection after tension-free inguinal hernia repair with polypropylene mesh: the randomized, double-blind, prospective trial. Ann Surg. 2001;233(1):26–33. doi: 10.1097/00000658-200101000-00005.
    1. ABX Guide. .
    1. Antimicrobial prophylaxis in surgery. Med Lett Drugs Ther. 1997;39:97–101.
    1. Bratzler DW, Houck PM. Antimicrobial prophylaxis for surgery: an advisory statement from the National Surgical Infection Prevention Project. Clin Infect Dis. 2004;38(12):1706–1715. doi: 10.1086/421095.
    1. McKittrick LS, Wheelock FC Jr. The routine use of antibiotics in elective abdominal surgery. Surg Gynecol Obstet. 1954;99(3):376–377.
    1. Burke JF. The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery. 1961;50:161–168.
    1. Stone HH, Hooper CA, Kolb LD, Geheber CE, Dawkins EJ. Antibiotic prophylaxis in gastric, biliary and colonic surgery. Ann Surg. 1976;184(4):443–452. doi: 10.1097/00000658-197610000-00007.
    1. DiPiro JT, Vallner JJ, Bowden TA Jr, Clark BA, Sisley JF. Intraoperative serum and tissue activity of cefazolin and cefoxitin. Arch Surg. 1985;120(7):829–832. doi: 10.1001/archsurg.1985.01390310067015.
    1. Friedman RJ, Friedrich LV, White RL, Kays MB, Brundage DM, Graham J. Antibiotic prophylaxis and tourniquet inflation in total knee arthroplasty. Clin Orthop Relat Res. 1990;260:17–23.
    1. Martin C, Ragni J, Lokiec F, Guillen JC, Auge A, Pecking M, Gouin F. Pharmacokinetics and tissue penetration of a single dose of ceftriaxone (1,000 milligrams intravenously) for antibiotic prophylaxis in thoracic surgery. Antimicrob Agents Chemother. 1992;36(12):2804–2807. doi: 10.1128/AAC.36.12.2804.
    1. Classen DC, Evans RS, Pestotnik SL, Horn SD, Menlove RL, Burke JP. The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J Med. 1992;326(5):281–286. doi: 10.1056/NEJM199201303260501.
    1. Geroulanos S, Marathias K, Kriaras J, Kadas B. Cephalosporins in surgical prophylaxis. J Chemother. 2001;1:23–26.
    1. Vuorisalo S, Haukipuro K, Pokela R, Syrjälä H. Risk features for surgical-site infections in coronary artery bypass surgery. Infect Control Hosp Epidemiol. 1998;19(4):240–247. doi: 10.2307/30142414.
    1. National Nosocomial Infections Surveillance (NNIS) System report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control. 2004;32(8):470–485. doi: 10.1016/j.ajic.2004.10.001.
    1. Steinberg JP, Braun BI, Hellinger WC, Kusek L, Bozikis MR, Bush AJ, Dellinger EP, Burke JP, Simmons B, Kritchevsky SB. Trial to Reduce Antimicrobial Prophylaxis Errors (TRAPE) Study Group. Timing of antimicrobial prophylaxis and the risk of surgical site infections: results from the Trial to Reduce Antimicrobial Prophylaxis Errors. Ann Surg. 2009;250(1):10–16. doi: 10.1097/SLA.0b013e3181ad5fca.
    1. Van Kasteren ME, Mannien J, Ott A, Kullberg BJ, de Boer AS, Gyssens IC. Antibiotic prophylaxis and the risk of surgical site infections following total hip arthroplasty: timely administration is the most important factor. Clin Infect Dis. 2007;44(7):921–927. doi: 10.1086/512192.
    1. Vogel F, Naber KG, Wacha H, Shah P. Parenterale Antibiotika bei Erwachsenen. Chemother J. 1999;8:3–49.
    1. Kujath P, Bouchard R, Scheele J, Esnaashari H. Neues in der perioperativen antibiotischen Prophylaxe. Chirurg. 2006;77:490–498. doi: 10.1007/s00104-006-1194-3.
    1. Davies AJ, Lockley RM, Jones A, el-Safty M, Clothier JC. Comparative pharmacokinetics of cefamandole, cefuroxime and cephradine during total hip replacement. J Antimicrob Chemother. 1986;17(5):637–640. doi: 10.1093/jac/17.5.637.
    1. Maier W, Strutz J. Concentration of cephalosporins in tissues of the head and neck after parenteral infusion. Chemotherapy. 1995;41(6):421–426. doi: 10.1159/000239377.
    1. Alfter G, Schwenzer N, Friess D, Möhrle E. Perioperative antibiotic prophylaxis with cefuroxime in oral-maxillofacial surgical procedures. J Craniomaxillofac Surg. 1995;23(1):38–41. doi: 10.1016/S1010-5182(05)80253-7.
    1. Hutschala D, Skhirtladze K, Kinstner C, Mayer-Helm B, Müller M, Wolner E, Tschernko EM. In vivo microdialysis to measure antibiotic penetration into soft tissue during cardiac surgery. Ann Thorac Surg. 2007;84(5):1605–1610. doi: 10.1016/j.athoracsur.2007.06.052.
    1. Garey KW, Dao T, Chen H, Amrutkar P, Kumar N, Reiter M, Gentry LO. Timing of vancomycin prophylaxis for cardiac surgery patients and the risk of surgical site infections. J Antimicrob Chemother. 2006;58(3):645–650. doi: 10.1093/jac/dkl279.
    1. Kasatpibal N, Norgaard M, Sorensen HT, Schønheyder HC, Jamulitrat S, Chongsuvivatwong V. Risk of surgical site infection and efficacy of antibiotic prophylaxis: a cohort study of appendectomy patients in Thailand. BMC Infect Dis. 2006;6:111. doi: 10.1186/1471-2334-6-111.
    1. Weber WP, Marti WR, Zwahlen M, Misteli H, Rosenthal R, Reck S, Fueglistaler P, Bolli M, Trampuz A, Oertli D, Widmer AF. The timing of surgical antimicrobial prophylaxis. Ann Surg. 2008;247(6):918–926. doi: 10.1097/SLA.0b013e31816c3fec.
    1. Weber WP, Zwahlen M, Reck S, Feder-Mengus C, Misteli H, Rosenthal R, Brandenberger D, Oertli D, Widmer AF, Marti WR. Economic burden of surgical site infections at a European university hospital. Infect Control Hosp Epidemiol. 2008;29(7):623–629. doi: 10.1086/589331.
    1. Misteli H, Weber WP, Reck S, Rosenthal R, Zwahlen M, Fueglistaler P, Bolli MK, Oertli D, Widmer AF, Marti WR. Surgical glove perforation and the risk of surgical site infection. Arch Surg. 2009;144(6):553–558. doi: 10.1001/archsurg.2009.60. discussion 558.
    1. Rosenthal R, Weber WP, Zwahlen M, Misteli H, Reck S, Oertli D, Widmer AF, Marti WR. Impact of surgical training on incidence of surgical site infection. World J Surg. 2009;33(6):1165–1173. doi: 10.1007/s00268-009-0012-8.
    1. Weber WP, Zwahlen M, Reck S, Misteli H, Rosenthal R, Buser AS, Kaufmann M, Oertli D, Widmer AF, Marti WR. The association of preoperative anemia and perioperative allogeneic blood transfusion with the risk of surgical site infection. Transfusion. 2009;49(9):1964–1970. doi: 10.1111/j.1537-2995.2009.02204.x.
    1. Misteli H, Widmer AF, Rosenthal R, Oertli D, Marti WR, Weber WP. Spectrum of pathogens in surgical site infections at a Swiss university hospital. Swiss Med Wkly. 2011;140:w13146.
    1. Rosenthal R, Weber WP, Marti WR, Misteli H, Reck S, Dangel M, Oertli D, Widmer AF. Surveillance of surgical site infections by surgeons: biased underreporting or useful epidemiological data? J Hosp Infect. 2010;75(3):178–182. doi: 10.1016/j.jhin.2009.10.028.
    1. Berry SM, Carlin BP, Lee JJ, Muller P. Bayesian Adaptive Methods for Clinical Trials. Boca Raton, FL: Chapman & Hall/CRC Biostatistics Series; 2010.

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