Assessing Clinical Effectiveness of Ceftolozane/Tazobactam, Ceftazidime/Avibactam, and Meropenem/Vaborbactam in Bacteremia: A Systematic Review and Meta-Analysis.

Background/

Objectives

Bacteremia poses a significant clinical challenge, often necessitating the off-label use of novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations such as Ceftolozane/Tazobactam (C/T), Ceftazidime/Avibactam (C/A), and Meropenem/Vaborbactam (M/V). Despite their widespread use, no conclusive data support their effectiveness in bacteremia. This meta-analysis aims to evaluate the clinical effectiveness of C/T, C/A, and M/V in treating bacteremia, with a focus on survival outcomes and clinical cure rates.

Methods

A systematic review and meta-analysis were conducted following a comprehensive search of Scopus and PubMed databases. Studies reporting survival and clinical cure rates in patients treated with C/T, C/A, or M/V for bacteremia were included. Data extraction followed predefined criteria, and a random-effects meta-analysis was performed to synthesize the findings.

Results

Twenty studies met the inclusion criteria, with 18 reporting survival outcomes and 10 evaluating clinical cure rates. The pooled survival and clinical cure rates were 73.6% (95% CI: 67.5-79.8%, p < 0.001) and 76.2% (95% CI: 69.2-83.3%, p < 0.001), respectively, both exhibiting moderate heterogeneity. Subgroup analyses revealed consistent survival trends across study quality, with low- and high-risk-of-bias studies demonstrating comparable estimates. Given that C/A was the most frequently studied agent, its dedicated subgroup analysis yielded a pooled survival estimate of 73.4% (95% CI: 66.4-80.3%, p < 0.001).

Conclusions

This meta-analysis provides supporting evidence for the clinical effectiveness of C/T, C/A, and M/V in bacteremia reinforcing the role of BL/BLIs in antimicrobial stewardship as viable options for resistant infections. However, further randomized controlled trials (RCTs) are warranted to validate these results and refine treatment strategies for bacteremia.