Global evaluation of the antibacterial activity of Ceftolozane/Tazobactam against ESBLs-producing Escherichia coli and Klebsiella pneumoniae: a systematic review and meta-analysis

Abstract

Background: Ceftolozane/Tazobactam is a β-lactam/β-lactamase inhibitor combination with a high range of efficacy and broad-spectrum action against multidrug-resistant bacterial strains. Objectives: The present study aimed to analyze the in vitro activity of Ceftolozane/Tazobactam against extended-spectrum β-lactamases (ESBLs)-producing Escherichia coli (ESBLs-EC) and Klebsiella pneumonia (ESBLs-KP) in the published literature to provide international data on the antimicrobial stewardship programs. Design: Systematic review and meta-analysis. Methods: A systematic literature search was conducted on the Web of Science, Embase, PubMed, Scopus, and Google Scholar electronic databases from the beginning of databases to December 2022 to cover all published articles relevant to our scope. Results: At last, 31 publications that met our inclusion criteria were selected for data extraction and analysis by Comprehensive Meta-Analysis Software. The pooled prevalence of Ceftolozane/Tazobactam susceptibility for ESBLs-EC and ESBLs-KP was estimated at 91.3% [95% confidence interval (CI): 90.1–92.5%] and 65.6% (95% CI: 60.8–70.2%), respectively. There was significant heterogeneity among the 31 studies for ESBLs-EC (χ2 = 91.621; p < 0.001; I2 = 67.256%) and ESBLs-KP (χ2 = 348.72; p < 0.001; I2 = 91.4%). Most clinical isolates of ESBLs-EC had MIC50 and MIC90 at a concentration of 0.5 and 2 µg/mL [minimum inhibitory concentration (MIC) at which 50% and 90% of isolates were inhibited], respectively. In contrast, most clinical isolates of ESBLs-KP had MIC50 and MIC90 at a concentration of 1 and 32 µg/mL, respectively. Conclusion: Based on the meta-analysis results, Ceftolozane/Tazobactam has a more promising in vitro antibacterial activity against ESBLs-EC isolates from different clinical sources than ESBLs-KP isolates. Therefore, Ceftolozane/Tazobactam can be a useful therapeutic drug as an alternative to carbapenems. Randomized clinical trials are needed to provide clinical evidence to support these observations.