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.

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 .

• Authors: Andrew Kirby, Eduardo Asín-Prieto, Flora Agnes Burns, Duncan Ewin, Kavi Fatania, Mithun Kailavasan, Saira Nisar, Agamemnon Pericleous, Iñaki F Trocóniz, Dermot Burke
• Journal: European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology (Eur J Clin Microbiol Infect Dis) Vol. 38 Issue 2 Pg. 357-363 (Feb 2019) ISSN: 1435-4373 [Electronic] Germany
• PMID: 30519893 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Anti-Bacterial Agents
• Metronidazole
• Cefuroxime

Topics

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