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 toward cefiderocol in a patient with intra-abdominal and bloodstream infections caused 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.