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

Eur J Clin Microbiol Infect Dis. 2019 Feb;38(2):357-363. doi: 10.1007/s10096-018-3435-z. Epub 2018 Dec 5.

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.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Intravenous
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Antibiotic Prophylaxis*
  • Bacteria / drug effects
  • Bacteria / isolation & purification
  • Cefuroxime / blood
  • Cefuroxime / pharmacology
  • Cefuroxime / therapeutic use*
  • Colorectal Surgery / adverse effects
  • Colorectal Surgery / methods*
  • Feasibility Studies
  • Female
  • Humans
  • Male
  • Metronidazole / blood
  • Metronidazole / pharmacology
  • Metronidazole / therapeutic use
  • Microbial Sensitivity Tests
  • Middle Aged
  • Perioperative Care
  • Pilot Projects
  • Surgical Wound Infection / drug therapy
  • Surgical Wound Infection / microbiology
  • Surgical Wound Infection / prevention & control*
  • Treatment Outcome
  • United Kingdom

Substances

  • Anti-Bacterial Agents
  • Metronidazole
  • Cefuroxime

Associated data

  • ClinicalTrials.gov/NCT02445859