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.