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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| Vydané v: | International journal of infectious diseases Ročník 151; s. 107321 |
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| Hlavní autori: | , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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Canada
Elsevier Ltd
01.02.2025
Elsevier |
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| ISSN: | 1201-9712, 1878-3511, 1878-3511 |
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| Abstract | •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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| AbstractList | •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. 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. 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.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. 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 (bla and bla ). 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. 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 beta-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 flu genes. The combination of a metallo-beta-lactamase background and mutations in siderophore receptors was associated with phenotypic resistance to cefiderocol. |
| ArticleNumber | 107321 |
| Author | Thille, Arnaud W. Marchand, Sandrine Arrivé, François Deroche, Luc Barraud, Olivier Rozenholc, Albane Moal, Gwenaël Le Martellosio, Jean-Philippe Buyck, Julien M. |
| Author_xml | – sequence: 1 givenname: Luc surname: Deroche fullname: Deroche, Luc organization: Université de Poitiers, PHAR2, Inserm U1070, Poitiers, France – sequence: 2 givenname: Albane surname: Rozenholc fullname: Rozenholc, Albane organization: Université de Poitiers, PHAR2, Inserm U1070, Poitiers, France – sequence: 3 givenname: François surname: Arrivé fullname: Arrivé, François organization: CHU de Poitiers, Service de Médecine Intensive - Réanimation, Poitiers, France – sequence: 4 givenname: Jean-Philippe orcidid: 0000-0003-0886-7699 surname: Martellosio fullname: Martellosio, Jean-Philippe organization: CHU de Poitiers, Service de Médecine Interne, maladies infectieuses et tropicales, Poitiers, France – sequence: 5 givenname: Gwenaël Le surname: Moal fullname: Moal, Gwenaël Le organization: CHU de Poitiers, Service de Médecine Interne, maladies infectieuses et tropicales, Poitiers, France – sequence: 6 givenname: Arnaud W. surname: Thille fullname: Thille, Arnaud W. organization: CHU de Poitiers, Service de Médecine Intensive - Réanimation, Poitiers, France – sequence: 7 givenname: Olivier surname: Barraud fullname: Barraud, Olivier organization: Université Limoges, INSERM, CHU Limoges, UMR 1092, Limoges, France – sequence: 8 givenname: Sandrine surname: Marchand fullname: Marchand, Sandrine organization: Université de Poitiers, PHAR2, Inserm U1070, Poitiers, France – sequence: 9 givenname: Julien M. orcidid: 0000-0003-0299-4654 surname: Buyck fullname: Buyck, Julien M. email: julien.buyck@univ-poitiers.fr organization: Université de Poitiers, PHAR2, Inserm U1070, Poitiers, France |
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| Snippet | •Cefiderocol resistance occurred during treatment of an NDM-5 Klebsiella pneumoniae.•Simultaneous resistance emerged by two isogenic isolates with varying cirA... Cefiderocol, a siderophore-conjugated cephalosporine, is a promising drug used to treat infection with carbapenem-resistant gram-negative bacteria. Here, we... |
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| SubjectTerms | 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 |
| Title | Emergence of cefiderocol resistance during therapy in NDM-5–producing Klebsiella pneumoniae isolates harboring siderophore receptors mutations |
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