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

This study evaluated the efficacy of novel β-lactam/β-lactamase (NβL/βLIs) combination against Enterobacteriaceae and Pseudomonas aeruginosa infections.

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.

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; I² =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.

Novel βL/-βLIs are as effective as BAT in treating Enterobacteriaceae and P. aeruginosa infections, including MDR strains.