Efficacy and safety of novel β-lactam/β-lactamase inhibitor combinations for the treatment of complicated urinary tract infections or acute pyelonephritis: A systematic review and meta-analysis.

OBJECTIVES

The increasing resistance of gram-negative bacteria in complicated urinary tract infections (cUTI) and acute pyelonephritis (APN) poses major treatment challenges. This study aimed to evaluated the efficacy and safety of novel β-Lactam/β-Lactamase inhibitor combinations compared with conventional antibiotics.

METHODS

We systematically searched PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and FDA.gov for randomized controlled trials (RCTs) published up to July 15, 2025. Eligible studied included patients with cUTI or APN. Primary outcomes were clinical and microbiological response rates at the test-of-cure (TOC) or the end-of-treatment visit. Secondary outcomes included adverse events (AEs), serious AEs (SAEs), and treatment discontinuations due to AEs. Risk of bias was assessed using the Cochran tool.

RESULTS

Eleven RCTs with a total of 4986 patients (2719 in the experimental group and 2267 in the control group) were included. Novel β-Lactam/β-Lactamase inhibitors significantly improved clinical response in the microbiological modified intent-to-treat population (OR = 1.64, 95% CI [1.43-1.88], P < 0.001). The incidence of overall AEs and SAEs was similar between groups, though drug-related AEs were more common in the experimental group (OR = 1.38, 95% CI [1.11-1.72], P = 0.003).

CONCLUSIONS

Novel β-Lactam/β-Lactamase inhibitor combinations demonstrated superior efficacy and comparable safety to conventional antibiotics in treating cUTI and APN, particularly at the TOC stage.