The role of β-lactam/β-lactamase inhibitor combinations in multidrug-resistant bacterial infections: a comprehensive meta-analysis.

Background: Multidrug-resistant (MDR) bacterial infections pose a global public health challenge. β-Lactam/β-lactamase inhibitor combinations (BLIs) are essential for treating MDR infections, although their efficacy varies across studies. This meta-analysis aims to evaluate their clinical value.

Methods: A systematic search of PubMed, Embase, and Cochrane Library was conducted for randomized controlled trials (RCTs) on BLIs for MDR bacterial infections published from January 2000 to December 2024. Study quality was assessed using the Cochrane Risk of Bias tool, and meta-analysis was performed using RevMan 5.4. Primary outcomes included clinical efficacy rate, bacterial clearance rate, and incidence of adverse reactions.

Results: Eighteen high-quality RCTs involving 2,356 patients were included. BLIs showed a significantly higher clinical efficacy rate (76.23%) than controls (62.45%) (RR=1.59, 95% CI: 1.44-1.73, P<0.001) and bacterial clearance rate (71.58% vs. 58.67%, RR=1.21, 95% CI: 1.16-1.26, P<0.001). Subgroup analysis revealed clinical efficacy rates of 73.45% for carbapenem-resistant Enterobacteriaceae (CRE) and 78.32% for ESBL-producing Enterobacteriaceae, with bacterial clearance rates of 68.72% and 74.11%, respectively. The adverse reaction rate in the BLI group was 15.68% (mainly diarrhea, nausea, rash), which was not significantly different from the control group (17.89%, RR=0.96, 95% CI: 0.85-1.07, P=0.977).

Conclusion: BLIs demonstrate high efficacy, bacterial clearance, and safety in treating MDR infections, particularly CRE and ESBL infections. Larger multicenter RCTs are needed for further validation.