Effect of oral antimicrobial prophylaxis on surgical site infection after elective colorectal surgery: multicentre, randomised, double blind, placebo controlled trial

Abstract

Objective To investigate whether oral antimicrobial prophylaxis as an adjunct to intravenous antibiotic prophylaxis reduces surgical site infections after elective colorectal surgery. Design Multicentre, randomised, double blind, placebo controlled trial. Setting 11 university and non-university hospitals in France between 25 May 2016 and 8 August 2019. Participants 926 adults scheduled for elective colorectal surgery. Intervention Patients were randomised to receive either a single 1 g dose of ornidazole (n=463) or placebo (n=463) orally 12 hours before surgery, in addition to intravenous antimicrobial prophylaxis before surgical incision. Main outcome measures The primary outcome was the proportion of patients with surgical site infection within 30 days after surgery. Secondary outcomes included individual types of surgical site infections and major postoperative complications (Clavien-Dindo classification grade 3 or higher) within 30 days after surgery. Results Of the 960 patients who were enrolled, 926 (96%) were included in the analysis. The mean age of participants was 63 years and 554 (60%) were men. Surgical site infection within 30 days after surgery occurred in 60 of 463 patients (13%) in the oral prophylaxis group and 100 of 463 (22%) in the placebo group (absolute difference −8.6%, 95% confidence interval −13.5% to −3.8%; relative risk 0.60, 95% confidence interval 0.45 to 0.80). The proportion of patients with deep infections was 4.8% in the oral prophylaxis group and 8.0% in the placebo group (absolute difference −3.2%, 95% confidence interval −6.4% to −0.1%). The proportion of patients with organ space infections was 5.0% in the oral prophylaxis group and 8.4% in the placebo group (absolute difference −3.4%, −6.7% to −0.2%). Major postoperative complications occurred in 9.1% patients in the oral prophylaxis group and 13.6% in the placebo group (absolute difference −4.5%, −8.6% to −0.5%). Conclusion Among adults undergoing elective colorectal surgery, the addition of a single 1 g dose of ornidazole compared with placebo before surgery significantly reduced surgical site infections. Trial registration ClinicalTrials.gov NCT02618720 .

Oral antibiotics and mechanical bowel preparation for colorectal surgery: a prospective observational study of surgical site infection and microbial analysis

“…While this study might be underpowered, differences with the current study cohort could also be ascribed to a control arm without MBP and the single dose regimen used, perhaps not su cient to impact the gut microbiome. A French trial comprising colorectal resections compared ornidazole only versus placebo and found an SSI difference of 22 vs 13%, while the subset of patients with MBP had an even greater bene t from OAB [27]. While strengthening the hypothesis that OAB and MBP in combination are bene cial, in the current study clear SSI improvements were suggested only in the dual OAB group, which might be explained the admittedly weaker study design.…”

Preoperative oral antibiotic administration in patients undergoing curative resection with stoma creation for colorectal cancer: effectiveness in preventing surgical site infection and the possibility of peristomal candidiasis induced by enterobacterial alteration

“…However, there is no consensus on the type and optimal dosage of antibiotics to be used. Futier et al have reported the SSI suppressive effect of a single 1000 mg dose of ornidazole in a multicentre, double‐blind, randomized trial [18]. Papp et al also conducted a prospective multicentre study and reported that preoperative oral administration of 1500 mg of MNZ and 3000 mg of neomycin can prevent SSI [19].…”

Antimicrobial Prophylaxis with Ampicillin-sulbactam Compared with Cefazolin for Esophagectomy

“…Previous animal studies on colorectal surgery have shown that the gut microbiome, whose composition and function are affected by antimicrobial prophylaxis, plays a major role in anastomotic healing 43,44 . A recent multicenter, double-blind, randomized trial investigating colorectal surgery (n=926) showed that enhanced anaerobic coverage in antimicrobial prophylaxis (addition of a single dose of ornidazole to cefoxitin) significantly reduced anastomotic leakage [relative risk, 0.59 (0.36–0.99)] as well as SSI [0.60 (0.45–0.80)] 8 . Although there would be a time lag between the use of antibiotic prophylaxis and the occurrence of anastomotic leakage, even single-dose antibiotics can reportedly change the composition of the gut microbiome for approximately 1 week 45,46 .…”