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Emergence of cefiderocol resistance during therapy in NDM-5–producing Klebsiella pneumoniae isolates harboring siderophore receptors mutations

Autor: Luc Deroche, Albane Rozenholc, François Arrivé, Jean-Philippe Martellosio, Gwenaël Le Moal, Arnaud W. Thille, Olivier Barraud, Sandrine Marchand, Julien M. Buyck
Jazyk: angličtina
Rok vydání: 2025
Předmět:
Zdroj: International Journal of Infectious Diseases, Vol 151, Iss , Pp 107321- (2025)
Druh dokumentu: article
ISSN: 1201-9712
DOI: 10.1016/j.ijid.2024.107321
Popis: Cefiderocol, a siderophore-conjugated cephalosporine, is a promising drug used to treat infection with carbapenem-resistant gram-negative bacteria. Here, we report a case of pneumonia induced by multiple gram-negative pathogens, including a carbapenem-resistant Klebsiella pneumoniae developing cefiderocol resistance within 32 days of cefiderocol therapy. Whole genome sequencing of three consecutive K. pneumoniae isolates revealed that the bacteria were isogenic and were carrying several broad-spectrum β-lactamases (blaNDM5 and blaCTX-M-15). Two isolates with elevated minimum inhibitory concentration against cefiderocol harbored mutations in genes encoding siderophore: one in the cirA gene and one in both the cirA and the fiu genes. The combination of a metallo-β-lactamase background and mutations in siderophore receptors was associated with phenotypic resistance to cefiderocol.
Databáze: Directory of Open Access Journals
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