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

•Cefiderocol resistance occurred during treatment of an NDM-5 Klebsiella pneumoniae.•Simultaneous resistance emerged by two isogenic isolates with varying cirA mutations.•One isolate harbored mutations in two siderophores receptor genes (cirA and fiu).•Cefiderocol susceptibility testing remains chal...

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Bibliographic Details
Published in:International journal of infectious diseases Vol. 151; p. 107321
Main Authors: Deroche, Luc, Rozenholc, Albane, Arrivé, François, Martellosio, Jean-Philippe, Moal, Gwenaël Le, Thille, Arnaud W., Barraud, Olivier, Marchand, Sandrine, Buyck, Julien M.
Format: Journal Article
Language:English
Published: Canada Elsevier Ltd 01.02.2025
Elsevier
Subjects:
Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - therapeutic use
Antibiotic resistance
Bacterial Outer Membrane Proteins - genetics
Bacterial Outer Membrane Proteins - metabolism
beta-Lactamases - metabolism
Cefiderocol
Cefiderocol - pharmacology
Cefiderocol - therapeutic use
Cephalosporins - pharmacology
Cephalosporins - therapeutic use
Drug Resistance, Multiple, Bacterial - genetics
Humans
Klebsiella Infections - drug therapy
Klebsiella Infections - microbiology
Klebsiella pneumoniae
Klebsiella pneumoniae - drug effects
Klebsiella pneumoniae - enzymology
Klebsiella pneumoniae - genetics
Klebsiella pneumoniae - isolation & purification
Life Sciences
Microbial Sensitivity Tests
Mutation
Receptors, Cell Surface - genetics
Siderophore receptor
Siderophores - pharmacology
Siderophores - therapeutic use
WGS
Whole Genome Sequencing
WGS
Cefiderocol
Siderophore receptor
Klebsiella pneumoniae
Antibiotic resistance
ISSN:1201-9712, 1878-3511, 1878-3511
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Summary:•Cefiderocol resistance occurred during treatment of an NDM-5 Klebsiella pneumoniae.•Simultaneous resistance emerged by two isogenic isolates with varying cirA mutations.•One isolate harbored mutations in two siderophores receptor genes (cirA and fiu).•Cefiderocol susceptibility testing remains challenging in clinical settings.•Cefiderol combination therapy should be considered on K. pneumoniae with high minimum inhibitory concentrations. 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.
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ISSN:1201-9712
1878-3511
1878-3511
DOI:10.1016/j.ijid.2024.107321