Effectiveness of novel β-lactams for Pseudomonas aeruginosa infection: A systematic review and meta-analysis

Abstract

Background: Novel β-lactams have in vitro activity against Pseudomonas aeruginosa (PA), but their clinical performances and the selection criteria for practical use are still not clear. We aimed to evaluate the efficacy of novel β-lactams for PA infection in various sites and to compare the efficacy of each agent.

Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science for randomized controlled trials that used novel β-lactams to treat PA infection. The primary outcomes were clinical cure and favorable microbiological response. Subgroup analyses were performed based on drug type, drug resistance of pathogens, and site of infection. Network meta-analysis was carried out within a Bayesian framework.

Results: In all studies combined (16 randomized controlled trials), novel β-lactams indicated comparable performance to other treatment regimens in both outcome measures (relative risk = 1.04; 95% confidence interval 0.94-1.15; P = .43) (relative risk = 0.97; 95% confidence interval 0.81-1.17; P = .76). Subgroup analyses showed that the efficacy of ceftolozane-tazobactam (TOL-TAZ), ceftazidime-avibactam (CAZ-AVI), imipenem-cilastatin-relebactam, and cefiderocol had no apparent differences compared to control groups among different infection sites, drug types and drug resistance of PA. In network meta-analysis, the results showed no statistically significant differences between TOL-TAZ, CAZ-AVI, and cefiderocol.

Conclusions: TOL-TAZ, CAZ-AVI, imipenem-cilastatin-relebactam, and cefiderocol are not inferior to other agents in the treatment of PA infection. Their efficacy is also comparable between TOL-TAZ, CAZ-AVI, and cefiderocol.

Keywords: Cefiderocol; Ceftazidime-avibactam; Ceftolozane-tazobactam; Efficacy; Imipenem-cilastatin-relebactam; Meropenem-vaborbactam.