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Randomized Controlled Trial
. 2020 Jun 15;9(1):84.
doi: 10.1186/s13756-020-00745-2.

Prevention of severe infectious complications after colorectal surgery using oral non-absorbable antimicrobial prophylaxis: results of a multicenter randomized placebo-controlled clinical trial

Tessa Mulder  1 , Marjolein Kluytmans-van den Bergh  1   2   3 , Bart Vlaminckx  4 , Daphne Roos  5 , Anne Marie de Smet  6 , Robert de Vos Tot Nederveen Cappel  7 , Paul Verheijen  8 , Alexandra Brandt  9 , Anke Smits  10 , Eric van der Vorm  11 , Erik Bathoorn  12 , Boudewijn van Etten  13 , Jacobien Veenemans  14 , Annemarie Weersink  15 , Margreet Vos  16 , Nils van 't Veer  17 , Stavros Nikolakopoulos  1 , Marc Bonten  1   18 , Jan Kluytmans  19   20
Affiliations
Randomized Controlled Trial

Prevention of severe infectious complications after colorectal surgery using oral non-absorbable antimicrobial prophylaxis: results of a multicenter randomized placebo-controlled clinical trial

Tessa Mulder et al. Antimicrob Resist Infect Control. .

Abstract

Background: Surgical site infections (SSIs) are common complications after colorectal surgery. Oral non-absorbable antibiotic prophylaxis (OAP) can be administered preoperatively to reduce the risk of SSIs. Its efficacy without simultaneous mechanical cleaning is unknown.

Methods: The Precaution trial was a double-blind, placebo-controlled randomized clinical trial conducted in six Dutch hospitals. Adult patients who underwent elective colorectal surgery were randomized to receive either a three-day course of preoperative OAP with tobramycin and colistin or placebo. The primary composite endpoint was the incidence of deep SSI or mortality within 30 days after surgery. Secondary endpoints included both infectious and non-infectious complications at 30 days and six months after surgery.

Results: The study was prematurely ended due to the loss of clinical equipoise. At that time, 39 patients had been randomized to active OAP and 39 to placebo, which reflected 8.1% of the initially pursued sample size. Nine (11.5%) patients developed the primary outcome, of whom four had been randomized to OAP (4/39; 10.3%) and five to placebo (5/39; 12.8%). This corresponds to a risk ratio in the intention-to-treat analysis of 0.80 (95% confidence interval (CI) 0.23-2.78). In the per-protocol analysis, the relative risk was 0.64 (95% CI 0.12-3.46).

Conclusions: Observational data emerging during the study provided new evidence for the effectiveness of OAP that changed both the clinical and medical ethical landscape for infection prevention in colorectal surgery. We therefore consider it unethical to continue randomizing patients to placebo. We recommend the implementation of OAP in clinical practice and continuing monitoring of infection rates and antibiotic susceptibilities.

Trial registration: The PreCaution trial is registered in the Netherlands Trial Register under NL5932 (previously: NTR6113) as well as in the EudraCT register under 2015-005736-17.

Keywords: Colorectal surgery; Infection control; Preoperative oral antibiotic prophylaxis; Surgical site infection.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Definitions of primary and secondary endpoints. SSIs were diagnosed with the CDC criteria [17]. CDC, Centers for Disease Control and Infection Prevention; ESBL-E, extended spectrum beta-lactamase producing Enterobacteriaceae; ICU, intensive care unit; SSI, surgical site infection
Fig. 2
Fig. 2
CONSORT flowchart of enrolment of participants. Logistical issues were unexpected changes in the date of surgery that led to insufficient time to complete the three-day intervention period (n = 1) or missed appointments for the informed consent procedure due last-minute changes in the outpatient clinic schedule (n = 3)
See this image and copyright information in PMC

References

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