Real-world multicentre study of cefiderocol treatment of immunocompromised patients with infections caused by multidrug-resistant Gram-negative bacteria: CEFI-ID.

Abstract

The increase in the population of immunocompromised patients due to advances in management of end-stage diseases and transplants poses challenges in treating infections caused by multi-drug resistant (MDR) pathogens. Cefiderocol (FDC), a siderophore cephalosporin, has shown efficacy against carbapenem-resistant Gram-negative bacteria. This retrospective multicentre study investigated the real-world use of FDC in 114 immunocompromised adults treated for MDR infections in 12 French hospitals (June 2020-November 2023). Clinical and microbiological outcomes, including infection cure, relapse, as well as mortality, and resistance acquisition, were assessed at days 28 and 90. Antibiotic prescription compliance with current guidelines were investigated. At day 28, clinical success was achieved in 53.3% of cases, and overall mortality was 37.7%, consistent with other studies (33-37%). Infection-related mortality accounted for 25.4%. Relapse occurred in 17.5% of patients by day 28, rising by an additional 9.8% among survivors by day 90. Resistance acquisition was observed in two cases at day 28 (Pseudomonas aeruginosa and Stenotrophomonas maltophilia) and in three additional cases by day 90. FDC was used as monotherapy in 49.1% of cases, with a median treatment duration of 10 days. Nearly 25% of strains collected in FDC-treated patients were susceptible to best practice alternatives. These findings highlight FDC's utility in difficult-to-treat infections, particularly S. maltophilia, but the high relapse rate and resistance acquisition underscore the need for careful monitoring, adherence to guidelines, and reconsideration of empirical use to prevent resistance and improve outcomes in fragile populations.