Continuous Antibiotic Prophylaxis in Colorectal Surgery

• Status: Completed
• Trial end date: 2017-05-01
• Target enrollment: 0
• Participant gender: All

Summary

We propose to randomise patients due to undergo colorectal surgery to standard antibiotic prophylaxis or an interventional antibiotic prophylaxis regimen and assess surgical wound infection rates. Standard antibiotic prophylaxis is a pre-operative injection of cefuroxime, repeated every 4 hours. The intervention regimen is a loading dose of cefuroxime followed by a continuous infusion of cefuroxime until the end of surgery. The intervention regimen dosing will be calculated using a patient's renal function and body weight. The intervention regimen will target a free serum drug concentration of 64mg/L. This serum level is 4x the MIC90 for colonising Enterobacteriaceae. The rational for this dosing regimen is summarised below. The primary objective of the study is to reduce by 50% the rate of surgical wound infections after colorectal surgery.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Leeds
• Treatments: Anti-Bacterial Agents; Antibiotics, Antitubercular; Cefuroxime; Cefuroxime axetil

Criteria

Inclusion criteria

• Undergoing colorectal surgery (incision, excision or anastomosis of the large bowel, including anastomosis of small to large bowel)

• Age >18.

• Expected duration of surgery > 2hours

• Creatinine clearance > 40 ml/min

• Cefuroxime/metronidazole are appropriate antibiotic prophylaxis regimens.

• Patient capable of giving informed consent

• Patients undergoing colorectal surgery plus additional surgery e.g. plastic surgery, urological surgery, gynaecological surgery.

• If it is not possible to obtain intra-operative blood samples e.g. difficult vascular access, or pre-operative swabs e.g. anatomy makes it difficult to obtain, patients will be included and this information treated as missing data. Patients on antibiotic treatment for an existing infection (except SSIs) can be included in the study

Exclusion Criteria:

• Unable to consent

• Pregnancy

• Expected duration of surgery <2hours

• Creatinine clearance <40ml/min

• Individual level microbiological advice for non cefuroxime based prophylaxis

• Cephalosporin allergy

• Penicillin allergy (hypersensitivity reaction only)

• Coumarin (warfarin and acenocoumarol) treatment

• Active blood borne virus infection e.g. HIV, hepatitis.

• Seizure history

• Concurrent use of probenecid

• Current participation in a research project aimed at reducing SSIs

• Antibiotics for treatment of a systemic Gram negative infection within 2 hours of initiation of surgery (Vancomycin, Teicoplanin, Daptomycin, Linezolid, Flucloxacillin. Nitrofurantoin and Clarithromycin would be permissible antibiotics without systemic Gram negative antibiotics).

• A current diagnosis of a SSI at the time of study entry.