Cefiderocol either in monotherapy or combination versus best available therapy in the treatment of carbapenem-resistant Acinetobacter baumannii infections: A systematic review and meta-analysis

Background: The best treatment for carbapenem-resistant Acinetobacter baumannii (CRAB) infections is still a matter of debate. Objectives: To describe the outcomes of patients treated with cefiderocol for CRAB infections, and to compare the efficacy of cefiderocol versus best available therapy (BAT). Data sources: We searched MEDLINE, the Cochrane Library and EMBASE to screen original reports published up to September 2023. Study eligibility criteria: Randomized controlled trials (RCTs) and observational studies investigating 30-day mortality, clinical failure, microbiological failure or rate of adverse drug reactions of patients treated with cefiderocol or BAT. Participants: Patients with infections due to CRAB. Interventions: Cefiderocol in monotherapy or in combination with other potentially active agents or BAT. Assessment of risk of bias: We used the Cochrane Risk of Bias Tool for RCTs, and the Newcastle Ottawa scale for observational studies. Methods of data synthesis: We conducted a meta-analysis pooling risk ratios (RRs) through random effect models. Results: We screened 801 original reports, and 18 studies (2 RCTs, 13 cohort studies and 3 case-series) were included in the analysis, for a total 733 patients treated with cefiderocol, and 473 receiving the BAT. Among patients receiving cefiderocol, the 30-day mortality rate was 42% (95% CI 38-47%), the rate of microbiological failure 48% (95% CI 31-65%), the clinical failure rate 43% (95% CI 32-55%), and the rate of ADRs was 3% (95% CI 1-6%). A lower mortality rate was observed among patients receiving cefiderocol monotherapy as compared to those treated with combination regimens (RR: 0.64; 95% CI: 0.43-0.94, p = 0.024). We found a significantly lower mortality rate (RR: 0.74; 95% CI: 0.57-0.95, p = 0.02) and a lower rate of ADRs (RR: 0.28; 95% CI: 0.09-0.91, p = 0.03) in the group treated with cefiderocol as compared to BAT. No difference was observed in microbiological and clinical failure rate. Conclusions: Our data strengthen the efficacy and safety profile of cefiderocol in CRAB infections. (c) 2024 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).