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Randomized Controlled Trial
. 2022 Nov 3:379:e071476.
doi: 10.1136/bmj-2022-071476.

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

Emmanuel Futier  1   2 , Samir Jaber  3   4 , Matthias Garot  5 , Marie Vignaud  6 , Yves Panis  7 , Karem Slim  8 , Jean-Christophe Lucet  9   10 , Gilles Lebuffe  5 , Alexandre Ouattara  11   12 , Younes El Amine  13 , Philippe Couderc  14 , Aurélien Dupré  15   16 , Audrey De Jong  3 , Sigismond Lasocki  17 , Marc Leone  18 , Julien Pottecher  19 , Bruno Pereira  20 , Catherine Paugam-Burtz  21 ; COMBINE study group
Affiliations
Randomized Controlled Trial

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

Emmanuel Futier et al. BMJ. .

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.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: the study was funded by a grant from the French Ministry of Health under its Clinical Research Program and by Clermont-Ferrand University Hospital; EF reports receiving consulting fees from Drager Medical, GE Healthcare, and Edwards Lifesciences, and honorariums for presentation from Baxter outside the submitted work; SJ reports receiving consulting fees from Drager Medical, Fisher & Paykel Healthcare, Fresenius Xenios, Medtronic, Baxter, and Mindray outside the submitted work; SL reports receiving consulting fees from Vifor Pharma and Alexys Sante, and honorariums for lectures from Vifor Pharma, Pharmacosmos, Pfizer, and Masimo outside the submitted work; ML reports receiving consulting fees from Gilead, Ambu, and LFB outside the submitted work; AO reports receiving consulting fees from LFB, Orion Pharma, Vifor Pharma, Nordic Pharma, and iSEP, and honorariums for lectures from Orion Pharma, Nordic Pharma, and LFB outside the submitted work. The authors declare no financial relationships with any organisations that might have an interest in the submitted work in the previous three years and no other relationships or activities that could appear to have influenced the submitted work.

Figures

Fig 1
Fig 1
Flow of participants through study. The per protocol population included patients from the modified intention-to-treat population, except those with one or more major protocol violations
Fig 2
Fig 2
Kaplan-Meier probability of surgical site infection (modified intention-to-treat population). Raw data for the Kaplan-Meier probability of surgical site infection were censored at 30 days after surgery (hazard ratio with oral prophylaxis versus placebo 0.57, 95% confidence interval 0.43 to 0.78). The Cox proportional-hazards model was unadjusted
Fig 3
Fig 3
Relative risks with 95% confidence intervals for the primary outcome of surgical site infection within 30 days after surgery in the oral prophylaxis group and placebo group, among all patients and in the two predefined subgroups. The widths of the confidence intervals for subgroup analyses were not adjusted for multiplicity and should not be used to infer definitive treatment effects. Mechanical bowel preparation consisted of polyethylene glycol or senna solution
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References

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