Examining the Clinical Efficacy of Novel Beta-Lactam and Beta-Lactamase Inhibitor Antibiotics: A Systematic Review and Meta-Analysis

Introduction: This study evaluated the efficacy of novel β-lactam/β-lactamase (NβL/βLIs) combination against Enterobacteriaceae and Pseudomonas aeruginosa infections. Methods: We searched CENTRAL, MEDLINE, Embase, CINAHL, Google Scholar, and clinical trial registries through April 20, 2025, and included randomized controlled trials (RCTs) comparing NβL/βLIs with best available therapy (BAT). Pediatric, noncomparative, and in vitro studies were excluded. We performed meta-analyses using random effects models to calculate odds ratios (OR) with 95% confidence intervals (CIs), summarized using GRADE methodology. We included 22 RCTs with 11,238 participants. All RCTs except one were conducted worldwide between 2012 and 2025. Approximately 52% of participants used novel β-lactamase inhibitors. Risk of bias (RoB) was assessed using the RoB 2 tool. Results: NβL/βLIs were as effective as BAT (OR 1.12, 95% CI 0.95–1.31; I 2 = 29%; 21 studies, 7630 participants). In multidrug resistance (MDR) infections, NβL/βLIs showed a trend toward benefit (OR 1.23, 95% CI 0.95–1.58; I ² =12%; 17 RCTs, 1713 participants). For microbiological cure, NβL/βLIs were superior (OR 1.33, 95% CI 1.06–1.66; I 2 = 68%; 22 studies), mainly due to improved efficacy in complicated tract infections. Safety outcomes were comparable between groups. Conclusions: Novel βL/-βLIs are as effective as BAT in treating Enterobacteriaceae and P. aeruginosa infections, including MDR strains.