Efficacy and safety of cefiderocol in the treatment of infections caused by Gram-negative bacteria: a systematic review and meta-analysis

Objective: To assess the efficacy and safety of cefiderocol (CFDC) in the treatment of Gram-negative bacteria (GNB) infections. Methods: Relevant studies were collected from PubMed, Web of Science, Cochrane, and Embase databases, from inception to 15 October 2023. The search formula was as follow: "cefiderocol", "S-649266", "Gram-Negative Bacteria", "Gram Negative Bacteria", "Klebsiella pneumoniae", "Hyalococcus pneumoniae", and "Bacterium pneumoniae proposal". Stata 15.0 software was employed to pool data with risk ratios (RRs) and 95% confidence intervals (CIs). Data were pooled using a random- or a fixed-effects model. Results: After a comprehensive study selection, 11 studies (5 RCTs and 7 observational studies) were retrieved that compared the efficacy of CFDC with other regimens, e.g., imipenem/cilastatin. The clinical response (RR = 1.00, 95% CI 0.94-1.08, I2 = 0%) and microbiological response (RR = 0.95 95% CI = 0.80-1.14, I2 = 68.7%) of CFDC were comparable to the control group. No significant differences were observed in mortality and adverse events. Furthermore, subgroup analyses showed that CFDC enhanced microbiological eradication in the follow-up group (RR = 1.25, 95% CI 1.05-1.49) and patients with complicated urinary tract infections (cUTI) (RR = 1.32, 95% CI 1.11- 1.57). Conclusions: CFDC is a novel iron-carrying cephalosporin with the potential to effectively combat Gram-negative bacterial infections. Additional large and high-quality RCTs are required to further confirm the safety of CFDC.