Meta-analysis: No benefit to continued antibiotic prophylaxis after surgery

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When best practice standards for surgical antibiotic prophylaxis were applied, postoperative continuation of antibiotic prophylaxis was found to have no benefit in reducing the risk of surgical site infection compared with immediate discontinuation, according to the results of a meta-analysis. Findings from this study provide an update to the evidence on which the 2016 World Health Organisation (WHO) recommendation against postoperative continuation of antibiotic prophylaxis was based.

Researchers at the Academic Medical Centre – University of Amsterdam, WHO Infection Prevention and Control Global Unit, University of Cincinnati College of Medicine, University of Bern, searched MEDLINE (PubMed), Embase, CINAHL, CENTRAL, and WHO regional medical databases for randomised controlled trials (RCTs) published from 1 January, 1990, to 24 July, 2018. The primary outcome was the effect of postoperative continuation vs immediate discontinuation of surgical antibiotic prophylaxis on the occurrence of surgical site infection.

The researchers included a pre-specified subgroup analysis for studies that did and did not adhere to current best practice standards for surgical antibiotic prophylaxis. Meeting best practice standards was defined as administering the first dose of antibiotic in the hour before incision and intra-operative re-dosing based on the half-life of the antibiotic and procedure duration.

Of the 83 RCTs included in the meta-analysis, 52 involving 19,273 participants were included in the primary analysis. Results showed an indication, but not conclusive evidence, of a benefit of postoperative continuation of antibiotic prophylaxis for the prevention of surgical site infection vs its immediate postoperative discontinuation (relative risk [RR], 0.89; 95% CI, 0.79-1.00), with low heterogeneity in effect size between studies.

In the subgroup analysis, adherence to best practice standards significantly modified the association between postoperative continuation of antibiotic prophylaxis and the incidence of surgical site infection. In the 27 RCTs that were not adherent to best practice standards, the continuation of antibiotic prophylaxis after surgery prevented surgical site infection compared with its immediate discontinuation (RR, 0.79; 95% CI, 0.67-0.94). However, when the analysis was restricted to the 24 RCTs that met best practice standards, no benefit was seen for postoperative continuation of antibiotic prophylaxis (RR, 1.04; 95% CI, 0.85-1.27; P =.048; 100% variance explained).

In an exploratory subgroup analysis, the researchers found some evidence that postoperative continuation of antibiotic prophylaxis might reduce the risk of surgical site infection associated with maxillofacial and cardiac surgeries. However, only 3 studies adhered to best practice standards in the maxillofacial surgery subgroup, and no studies adhered to standards for cardiac surgery.
The researchers noted that costs and adverse events were poorly reported, if at all, and no meaningful meta-analyses could be done to assess these outcomes.

“Future research to clarify the benefit of continuation of antibiotic prophylaxis beyond surgery, if any, should prespecify monitoring of adverse events, provide detailed data on costs, and standardise preoperative timing and intraoperative repeat administration of antibiotics,” concluded the researchers.

Abstract
Background: Antibiotic prophylaxis is frequently continued for 1 day or more after surgery to prevent surgical site infection. Continuing antibiotic prophylaxis after an operation might have no advantage compared with its immediate discontinuation, and it unnecessarily exposes patients to risks associated with antibiotic use. In 2016, WHO recommended discontinuation of antibiotic prophylaxis after surgery. We aimed to update the evidence that formed the basis for that recommendation.
Methods: For this systematic review and meta-analysis, we searched MEDLINE, Embase, CINAHL, CENTRAL, and WHO regional medical databases for randomised controlled trials (RCTs) on postoperative antibiotic prophylaxis that were published from Jan 1, 1990, to July 24, 2018. RCTs comparing the effect of postoperative continuation versus discontinuation of antibiotic prophylaxis on the incidence of surgical site infection in patients undergoing any surgical procedure with an indication for antibiotic prophylaxis were eligible. The primary outcome was the effect of postoperative surgical antibiotic prophylaxis continuation versus its immediate discontinuation on the occurrence of surgical site infection, with a prespecified subgroup analysis for studies that did and did not adhere to current best practice standards for surgical antibiotic prophylaxis. We calculated summary relative risks (RRs) with corresponding 95% CIs using a random effects model (DerSimonian and Laird). We evaluated heterogeneity with the χ 2 test, I 2, and τ 2, and visually assesed publication bias with a contour-enhanced funnel plot. This study is registered with PROSPERO, CRD42017060829.
Findings: We identified 83 relevant RCTs, of which 52 RCTs with 19 273 participants were included in the primary meta-analysis. The pooled RR of surgical site infection with postoperative continuation of antibiotic prophylaxis versus its immediate discontinuation was 0·89 (95% CI 0·79–1·00), with low heterogeneity in effect size between studies (τ 2=0·001, χ 2 p=0·46, I 2=0·7%). Our prespecified subgroup analysis showed a significant association between the effect estimate and adherence to best practice standards of surgical antibiotic prophylaxis: the RR of surgical site infection was reduced with continued antibiotic prophylaxis after surgery compared with its immediate discontinuation in trials that did not meet best practice standards (0·79 [95% CI 0·67–0·94]) but not in trials that did (1·04 [0·85–1·27]; p=0·048). Whether studies adhered to best practice standards explained all variance in the pooled estimate from the primary meta-analysis.
Interpretation: Overall, we identified no conclusive evidence for a benefit of postoperative continuation of antibiotic prophylaxis over its discontinuation. When best practice standards were followed, postoperative continuation of antibiotic prophylaxis did not yield any additional benefit in reducing the incidence of surgical site infection. These findings support WHO recommendations against this practice.

Authors
Stijn W de Jonge, Quirine J J Boldingh, Joseph S Solomkin, E Patchen Dellinger, Matthias Egger, Georgia Salanti, Benedetta Allegranzi, Marja A Boermeester

 

Infectious Diseases Advisor report

 

The Lancet Infectious Diseases abstract

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