Efficacy and safety of imipenem/cilastatin/relebactam (IMI/CS/REL): a meta-analysis of randomized controlled clinical trials.

Background: Relebactam is a new inhibitor of class A and class C β-lactamases. The FDA has approved combining IMI/CS/REL to treat some infectious diseases. This study systematically reviews the efficacy and safety of IMI/CS/REL based on existing clinical trials so as to provide a reference for follow-up research.

Methods: Researchers comprehensively searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for randomised controlled trials published up to Mar 28, 2025, with "Imipenem/Cilastatin/Relebactam" or "IMI/CS/REL" as keywords, and screened the results according to the proposed exclusion and inclusion criteria. Data extraction was performed on the included randomized controlled trials (RCTs), while the day 28/30 all-cause mortality, clinical response rate, microbiological response rate, the adverse event response rate and drug-related adverse reaction rate were evaluated using R (4.4.3). The evaluation results were expressed in terms of relative risk with 95% confidence limit (RR, 95%CI).

Results: Six RCTs (1606 subjects) were involved in this meta-analysis. The meta-analysis showed no significant differences between IMI/CS/REL and comparators in day 28/30 all-cause mortality (RR = 0.82, 95% CI 0.39-1.72, P = 0.10), in clinical response rate during the early follow-up period (EFU) (RR = 1.02, 95%CI 0.96-1.08, P = 0.67) and in microbiological response at EFU (RR = 1.02, 95%CI 0.95-1.09, P = 0.76). The adverse events (AEs) rate also showed no statistical difference in each study's arms (RR = 1.02, 95%CI 0.95-1.08, P = 0.87).

Conclusions: IMI/CS/REL demonstrates a non-inferior efficacy and safety profile compared to standard comparators in treating carbapenem-susceptible or carbapenem-resistant pathogens. Nevertheless, more robust clinical evidence-especially in resistant, polymicrobial, and pathogen-defined infections-is needed to fully establish its role in real-world practice.