Colo-Pro: a pilot randomised controlled trial to compare standard bolus-dosed cefuroxime prophylaxis to bolus-continuous infusion-dosed cefuroxime prophylaxis for the prevention of infections after colorectal surgery

Andrew Kirby, Eduardo Asín-Prieto, Flora Agnes Burns, Duncan Ewin, Kavi Fatania, Mithun Kailavasan, Saira Nisar, Agamemnon Pericleous, Iñaki F Trocóniz, Dermot Burke, Andrew Kirby, Eduardo Asín-Prieto, Flora Agnes Burns, Duncan Ewin, Kavi Fatania, Mithun Kailavasan, Saira Nisar, Agamemnon Pericleous, Iñaki F Trocóniz, Dermot Burke

Abstract

Standard bolus-dosed antibiotic prophylaxis may not inhibit growth of antibiotic resistant colonic bacteria, a cause of SSIs after colorectal surgery. An alternative strategy is continuous administration of antibiotic throughout surgery, maintaining concentrations of antibiotics that inhibit growth of resistant bacteria. This study is a pilot comparing bolus-continuous infusion with bolus-dosed cefuroxime prophylaxis in colorectal surgery. This is a pilot randomised controlled trial in which participants received cefuroxime bolus-infusion (intervention arm) targeting free serum cefuroxime concentrations of 64 mg/L, or 1.5 g cefuroxime as a bolus dose four-hourly (standard arm). Patients in both arms received metronidazole (500 mg intravenously). Eligible participants were adults undergoing colorectal surgery expected to last for over 2 h. Results were analysed on an intention-to-treat basis. The study was successfully piloted, with 46% (90/196) of eligible patients recruited and 89% (80/90) of participants completing all components of the protocol. A trialled bolus-continuous dosing regimen was successful in maintaining free serum cefuroxime concentrations of 64 mg/L. No serious adverse reactions were identified. Rates of SSIs (superficial and deep SSIs) were lower in the intervention arm than the standard treatment arm (24% (10/42) vs. 30% (13/43)), as were infection within 30 days of operation (41% (17/43) vs 51% (22/43)) and urinary tract infections (2% (1/42) vs. 9% (4/43)). These infection rates can be used to power future clinical trials. This study demonstrates the feasibility of cefuroxime bolus-continuous infusion of antibiotic prophylaxis trials, and provides safety data for infusions targeting free serum cefuroxime concentrations of 64 mg/L. Trial registration: NCT02445859 .

Keywords: Antibiotic; Bolus; Cefuroxime; Colorectal; Continuous, infusion; Prophylaxis.

Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1
Fig. 1
Free serum cefuroxime concentrations for 58 patients according to intervention treatment (compartment and non-compartment) and standard treatment dosing regimens. Horizontal lines represent 64 mg/L and 16 mg/L

References

    1. HES data: Health and Social Care Information Centre. Hospital Episode Statistics. . Accessed 11June 2018
    1. Kirby A, Burnside G, Bretsztajn L, Burke D. Post-operative infections following colorectal surgery in an English teaching hospital. Infect Dis (Lond) 2015;47:825–829. doi: 10.3109/23744235.2015.1055584.
    1. Petrosillo N, Drapeau CM, Nicastri E, Martini L, Ippolito G, Moro ML. Surgical site infections in Italian hospitals: a prospective multicenter study. BMC Infect Dis. 2008;8:4. doi: 10.1186/1471-2334-8-34.
    1. Smith RL, Bohl JK, Mcelearney ST, Friel CM, Barclay MM, Sawyer RG, Foley EF. Wound infection after elective colorectal resection. Ann Surg. 2004;239:599–605. doi: 10.1097/01.sla.0000124292.21605.99.
    1. Wick EC, Gibbs L, Indorf LA, Varma MG, Garcia-Aguilar J. Implementation of quality measures to reduce surgical site infection in colorectal patients. Dis Colon Rectum. 2008;51:1004–1009. doi: 10.1007/s10350-007-9142-y.
    1. Tanner J, Khan D, Aplin C, Ball J, Thomas M, Bankart J. Post-discharge surveillance to identify colorectal surgical site infection rates and related costs. J Hosp Infect. 2009;72:243–250. doi: 10.1016/j.jhin.2009.03.021.
    1. Jenks PJ, Laurent M, McQuarry S, Watkins R. Clinical and economic burden of surgical site infection (SSI) and predicted financial consequences of elimination of SSI from an English hospital. J Hosp Infect. 2014;86:24–33. doi: 10.1016/j.jhin.2013.09.012.
    1. Nelson RL, Gladman E, Barbateskovic M. Antimicrobial prophylaxis for colorectal surgery. Cochrane Database Syst Rev. 2014;5:CD001181.
    1. Itani KM, Jensen EH, Finn TS, Tomassini JE, Abramson MA. Effect of body mass index and ertapenem versus cefotetan prophylaxis on surgical site infection in elective colorectal surgery. Surg Infect. 2008;9:131–137. doi: 10.1089/sur.2007.034.
    1. Teillant A, Gandra S, Barter D, Morgan DJ, Laxminarayan R. Potential burden of antibiotic resistance on surgery and cancer chemotherapy antibiotic prophylaxis in the USA: a literature review and modelling study. Lancet Infect Dis. 2015;15:1429–1437. doi: 10.1016/S1473-3099(15)00270-4.
    1. Kirby A, Bretsztajn L, Santoni N, Patel H, Burke D, Horner C. Microbiological prediction of surgical site infection risk after colorectal surgery: a feasibility study. J Hosp Infect. 2015;90:271–272. doi: 10.1016/j.jhin.2015.03.002.
    1. Asín-Prieto E, Soraluce A, Trocóniz IF, Campo Cimarras E, Sáenz de Ugarte Sobrón J, Rodríguez-Gascón A, Isla A. Population pharmacokinetic models for cefuroxime and metronidazole used in combination as prophylactic agents in colorectal surgery: model-based evaluation of standard dosing regimens. Int J Antimicrob Agents. 2015;45:504–511. doi: 10.1016/j.ijantimicag.2015.01.008.
    1. MacGowan AP. Revisiting Beta-lactams - PK/PD improves dosing of old antibiotics. Curr Opin Pharmacol. 2011;11:470–476. doi: 10.1016/j.coph.2011.07.006.
    1. Nascimento JW, Carmona MJ, Strabelli TM, Auler JO, Jr, Santos SR. Perioperative cefuroxime pharmacokinetics in cardiac surgery. Clinics (Sao Paulo) 2007;62:257–260. doi: 10.1590/S1807-59322007000300009.
    1. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–612. doi: 10.7326/0003-4819-150-9-200905050-00006.
    1. Ogungbenro K, Aarons L. How many subjects are necessary for population pharmacokinetic experiments? Confidence interval approach. Eur J Clin Pharmacol. 2008;64:705–713. doi: 10.1007/s00228-008-0493-7.
    1. Mangram A, Horan TC, Pearson ML, Silver L, Jarvis WR. Guideline for prevention of surgical site infection. Am J Infect Control. 1999;27:97–132. doi: 10.1016/S0196-6553(99)70088-X.
    1. Public Health England. Surveillance of surgical site infections in NHS hospitals in England, 2016 to 2017. Public health England, December 2017. Available from: . Accessed 11 June 2017
    1. Health Protection Agency (2012) English national point prevalence survey on healthcare associated infections and antimicrobial use, 2011: preliminary data HPA, London
    1. Moher D, Hopewell S, Schulz KF, Montori V, Gøtzsche PC, Devereaux PJ, Elbourne D, Egger M, Altman DG. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c869. doi: 10.1136/bmj.c869.
    1. Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, Lancaster GA, PAFS consensus group CONSORT 2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016;355:i5239. doi: 10.1136/bmj.i5239.
    1. (EUCAST) ECoAST. Cefuroxime: rationale for the EUCAST clinical breakpoints (2010) . Accessed 11 June 2018
    1. Lovering AM, Perez J, Bowker KE, Reeves DS, MacGowan AP, Bannister G. A comparison of the penetration of cefuroxime and cephamandole into bone, fat and haematoma fluid in patients undergoing total hip replacement. J Antimicrob Chemother. 1997;40:99–104. doi: 10.1093/jac/40.1.99.
    1. Zelenitsky SA, Ariano RE, Harding GK, Silverman RE. Antibiotic pharmacodynamics in surgical prophylaxis: an association between intraoperative antibiotic concentrations and efficacy. Antimicrob Agents Chemother. 2002;46:3026–3030. doi: 10.1128/AAC.46.9.3026-3030.2002.
    1. Woodfield JC, Beshay N, van Rij AM. A meta-analysis of randomized, controlled trials assessing the prophylactic use of ceftriaxone. A study of wound, chest, and urinary infections. World J Surg. 2009;33:2538–2550. doi: 10.1007/s00268-009-0158-4.
    1. Shogan BD, Belogortseva N, Luong PM, Zaborin A, Lax S, Bethel C, Ward M, Muldoon JP, Singer M, An G, Umanskiy K, Konda V, Shakhsheer B, Luo J, Klabbers R, Hancock LE, Gilbert J, Zaborina O, Alverdy JC. Collagen degradation and MMP9 activation by Enterococcus faecalis contribute to intestinal anastomotic leak. Sci Transl Med. 2015;7:286ra68. doi: 10.1126/scitranslmed.3010658.

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