Cefiderocol-containing regimens versus best available therapy for carbapenem-resistant Acinetobacter infections

Abstract Purpose Carbapenem-resistant Acinetobacter baumannii (CRAB) poses an urgent therapeutic challenge worldwide as there are few treatment options available. Cefiderocol is a novel siderophore cephalosporin that has shown potent in vitro activity against A. baumannii. Published literature on the clinical use of cefiderocol for management of CRAB infections is limited with contradictory findings, contributing to a lack of consensus on optimal treatment regimens for CRAB. The objective of this study was to compare mortality in patients treated with cefiderocol-containing regimens versus best available therapy (BAT) for infections caused by CRAB. Methods This was a multicenter, retrospective, cohort study conducted from November 2021 through June 2023. Adult patients with CRAB infections confirmed by isolation of CRAB who received at least 48 hours of treatment active against CRAB were included. Patients with CRAB isolated from a urinary source or concomitant gram-positive bacteremia or fungemia were excluded. The primary outcome was inpatient mortality or discharge to hospice. Results Baseline characteristics were similar between the two groups except that more patients who received cefiderocol-containing regimens had bacteremia (21% vs 6%; P = 0.015, 95% CI, 0.02-0.28) and were on vasopressors (42% vs 19%; P = 0.011, 95% CI, 0.05-0.38). Patients with a CRAB infection treated with a cefiderocol-containing regimen had a statistically significant higher rate of inpatient mortality or discharge to hospice when compared to the BAT group (36% vs 14%; difference, 0.2 [95% CI, 0.06-0.38]; P = 0.005). Conclusion Patients treated with cefiderocol-containing regimens had a higher rate of inpatient mortality or discharge to hospice than those who received BAT.