Continuous Antibiotic Prophylaxis in Colorectal Surgery
Condition: Surgical Site Infection
MeSH terms: Infections; Surgical Wound Infection
Intervention: Cefuroxime 4 hourly bolus
Intervention description: Cefuroxime loading dose followed by a continuous infusion dosed according to renal function. Dosed to target a serum concentration of 64mg/L.
Intervention MeSH terms: Cefuroxime; Cefuroxime axetil
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 90.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Antibiotic; prophylaxis; surgical site infection

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.
    

Eligibility 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.