Rapid development of cefiderocol resistance in carbapenem-resistant Enterobacter cloacae during therapy is associated with heterogeneous mutations in the catecholate siderophore receptor cira.

We report a case of resistance development towards cefiderocol in a patient with intra-abdominal and bloodstream infections caued by carbapenemase-producing Enterobacter cloacae within 21 days of cefiderocol therapy. Whole genome sequencing revealed heterogeneous mutations in the cirA gene, encoding a catecholate siderophore receptor, conferring phenotypic resistance to cefiderocol.