Susceptibility Testing Is Key for the Success of Cefiderocol Treatment: A Retrospective Cohort Study

Abstract

Cefiderocol is a novel siderophore cephalosporin, which has proven in vitro activity against carbapenem-resistant (CR) Gram-negative pathogens and stability towards all carbapenemases. The aim of this study was to describe the first cases of prescriptions and the efficacy of cefiderocol for compassionate use in the 2 months following its access in France. We performed a national retrospective study of all patients who received at least one dose of cefiderocol from 2 November 2018 to 5 November 2019. We collected clinical characteristics and outcome through a standard questionnaire. Bacterial isolates from 12 patients were centralized and analyzed in the French National Reference Center for Antimicrobial Resistance, and sequenced using Illumina technology. Finally, 13 patients from 7 French university hospitals were included in the study. The main type of infection treated by cefiderocol was respiratory tract infections (RTI, n = 10). The targeted bacteria were Pseudomonas aeruginosa (n = 12), including carbapenemase-producing P. aeruginosa (n = 9), Acinetobacter baumannii (n = 2), Klebsiella pneumoniae (n = 1), and Enterobacter hormaechei (n = 1). Overall, of the 12 patients whose samples were analyzed, 5 P. aeruginosa strains were not susceptible to cefiderocol (4 categorized as resistant and 1 as intermediate) according to Clinical and Laboratory Standards Institute (CLSI) breakpoints. If considering susceptible strains, the cure rate was 6/7, while being 0/5 among not-susceptible strains. This study underlines the necessity to test strains in adequate conditions.

Keywords

• cefiderocol
• bacterial resistance
• carbapenem
• respiratory tract infection
• <i>Pseudomonas aeruginosa</i>