Reporting of antibiotic resistance in randomized controlled trials of new antibiotics: a systematic review.

BACKGROUND

Planning and reporting of antibiotic resistance at baseline and as an outcome in randomized controlled trials (RCTs) of new antibiotics is important for trial interpretation.

OBJECTIVES

To assess the planning and reporting of antibiotic susceptibility testing (AST) in recent RCTs of new antibiotics.

METHODS

Data sources: MEDLINE, EMBASE, Web of Science, Cochrane Central, and Ai2 Paper Finder were searched from January 2017 to July 2025, with no language restrictions; complemented by backward and forward citation screening for secondary publications and registry results, and the WHO antibacterial pipeline.

STUDY ELIGIBILITY CRITERIA: RCTs of new antibiotics listed in Phase 2/3 of the 2025 WHO antibacterial pipeline.

PARTICIPANTS

Adults and children with bacterial infections.

INTERVENTIONS: New antibiotics vs. any comparator.

ASSESSMENT OF RISK OF BIAS: Cochrane Risk of Bias 2.

METHODS OF DATA SYNTHESIS: Four prespecified resistance domains were extracted-real-time AST, central-laboratory baseline AST, AST-stratified primary efficacy outcome assessment, and assessment of resistance acquisition during follow-up. We calculated proportions of trials and arms with planning and reporting of each domain.

RESULTS

Fifty-seven RCTs evaluating 23 new antibiotics across 119 arms were included. Real-time baseline AST was reported in 17 of 57 (29.8%) trials, including 6 of 62 (9.7%) intervention and 17 of 57 (29.8%) comparator arms. Central-laboratory baseline AST was reported in 48 of 57 (84.2%). The primary efficacy outcome was stratified by baseline AST in 36 of 48 (75%) with available baseline AST data. Resistance acquisition was reported in 22 of 57 (38.6%) based on clinical infections; none of the trials conducted surveillance for resistance development. Only 2 of 57 trials planned to assess all four resistance domains, and only 9 of 57 reported results for all four domains.

CONCLUSIONS

In RCTs of antibiotics approved or in late-stage development since 2017, resistance assessment remained inconsistently planned and reported. Future trials should provide local laboratories with real-time AST tools, prespecify resistance-stratified analyses, and assess resistance acquisition through routine surveillance samples.