Clinical efficacy of cefiderocol-based regimens in patients with carbapenem-resistant Acinetobacter baumannii infections: A systematic review with meta-analysis

Objectives: To perform a systematic review with meta-analysis to assess the clinical efficacy of cefiderocol-based regimens for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections. Methods: Two authors independently searched PubMed-MEDLINE, Scopus, and Cochrane databases, from inception to 02 July 2023, for randomised controlled trials (RCTs) or observational studies comparing clinical efficacy of cefiderocol-based vs. non-cefiderocol-based regimens in patients with CRAB infections. Data were extracted by the two authors independently, and the quality of included studies was independently assessed using ROB 2.0 or ROBINS-I tools. Primary outcome was mortality rate. Meta-analysis was performed by pooling odds ratios (ORs) retrieved from studies providing adjustment for confounders using a random-effects model with the inverse variance method. Multiple subgroups and sensitivity analyses were conducted to investigate the source of heterogeneity. Results: A total of 530 articles were screened, and 6 studies (1 RCT and 5 observational; N = 561; 247 cefiderocol-based vs. 314 non-cefiderocol-based regimens) were included. Cefiderocol did not significantly reduce in-hospital mortality compared to alternative therapies (predominantly colistin-based), but the confidence intervals around the effect estimate included clinically important benefit (N = 5; OR 0.64; 95%CI 0.40-1.04; I2 = 57.5%). When only observational studies providing adjustment for confounders were considered, a lower risk of mortality was found in patients treated with cefiderocol-based regimens (N = 4; OR 0.53; 95%CI 0.39-0.71; I2 = 0.0%). Conclusions: Cefiderocol-based regimens were associated with a significantly lower risk of mortality in patients with CRAB infections in observational studies providing proper adjustment for confounders. (c) 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.