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Clinical Efficacy and Safety of Antibiotic Prophylaxis: An Umbrella Review of Meta-Analyses of Randomised Controlled Trials
25 Pages Posted: 12 Jan 2023
More...Abstract
Background: Antibiotic prophylaxis is an important part of antibiotic prescription and contributes to controversy and improper use. Considering the increasing global consumption of antibiotics and burden of antibiotic related adverse events. We aimed to comprehensively map the efficacy and safety of antibiotic prophylaxis through clinical scenarios and assess the strength of evidences.
Methods: In this umbrella review we searched PubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews to identify meta-analyses of randomised controlled trials (RCTs) evaluating the efficacy and safety of antibiotic prophylaxis compared to placebo or no treatment. We re-analysed meta-analyses including both RCTs and non-randomised studies of intervention (NRSIs) by removing NRSIs. We calculated effect estimates (relative risk [RR], 95% CI, 95% prediction interval, small study effects and excess significance biases). We also created an evidence map to summarise the absolute benefits of antibiotic prophylaxis in each scenario and certainty of evidences. This study is registered with PROSPERO, CRD42021292543.
Findings: 74 meta-analyses proved eligible with 721 RCTs and 77 clinical scenarios in three major classes. Of 118 health outcomes, 67 (56·8%) showed statistically significant benefits, 34 of which were supported by consistent or highly suggestive evidence from RCTs, and future studies are unlikely to change the direction of results. For clean surgeries, antibiotic prophylaxis may minimise infection occurrences in most surgeries except Mohs surgery, simple hand surgery, herniorrhaphy surgery, and thyroid surgery. For clean-contaminated surgeries, antibiotic prophylaxis benefited most surgeries and was particularly associated with 16 fewer surgical site infections (95% confidence interval [CI], 5 to 24 fewer) per 1000 persons after elective laparoscopic cholecystectomy, with high certainty evidence. Antibiotic prophylaxis showed benefits for all contaminated surgeries but may have little to no effect on the risk of anal fistula after incision and drainage of anorectal abscesses (Absolute risk reduction [ARR] 30 fewer per 1000 persons, 95% CI 200 fewer to 550 more), with very low certainty evidence. Antibiotic prophylaxis only showed benefits for cystoscopy, postoperative urinary catheterisation, mechanical ventilation, and urodynamic study in all 11 non-surgical invasive procedures. For non-procedural medical scenarios, antibiotic prophylaxis showed greater benefits in non-emergency scenarios, in which patients were mainly with weakened immune systems, or at risk of recurrent chronic infections. The safety profile of antibiotic prophylaxis from 21 systematic reviews showed that prophylactic antibiotics may increase the rate of antibiotic resistance or other adverse events in most scenarios and reach significance in cystoscopy, afebrile neutropenia following chemotherapy and hematopoietic stem cell transplantation.
Interpretation: The efficacy of prophylactic antibiotics varies widely across clinical scenarios. Safety profiles of prophylactic antibiotics were rarely reported with high heterogeneity. These findings call for systematic and transparent surveillance of prophylactic antibiotics for different scenarios.
Funding: This study was supported by 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University (Grant no ZYJC18015) and the Post-Doctor Research Project, West China Hospital, Sichuan University (Grant no 2020HXBH016). These funders had no role in the study design, writing of the manuscript, or decision to submit this or future manuscripts for publication. KW is funded by 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University (Grant no ZYJC18015). ZJ is funded by the Post-Doctor Research Project, West China Hospital, Sichuan University (Grant no 2020HXBH016).
Declaration of Interests: We declare no competing interests.
Keywords: Antibiotic prophylaxis, Antimicrobial stewardship, Antimicrobial resistance, Anti-bacterial agents, Umbrella review
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