Case Report and Genomic Analysis of Cefiderocol-Resistant Escherichia coli Clinical Isolates.

Abstract

Cefiderocol is a novel siderophore cephalosporin with in vitro activity against multidrug-resistant (MDR), gram-negative bacteria and intrinsic structural stability to all classes of carbapenemases. We sought to identify gene variants that could affect the mechanism of action (MOA) of cefiderocol. We report a case of bacteremia in a liver transplant candidate with a strain of carbapenem-resistant Escherichia coli that was found to be resistant to cefiderocol despite no prior treatment with this antimicrobial agent. Using whole-genome sequencing, we characterized the genomic content of this E coli isolate and assessed for genetic variants between related strains that were found to be cefiderocol susceptible. We identified several variants in genes with the potential to affect the mechanism of action of cefiderocol. The cefiderocol resistance in the E coli isolate identified in this study is likely due to mutations in the cirA gene, an iron transporter gene.