Emergence of cefiderocol resistance during therapy in NDM-5–producing Klebsiella pneumoniae isolates harboring siderophore receptors mutations
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 cefid...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | International Journal of Infectious Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1201971224003965 |
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| author | Luc Deroche Albane Rozenholc François Arrivé Jean-Philippe Martellosio Gwenaël Le Moal Arnaud W. Thille Olivier Barraud Sandrine Marchand Julien M. Buyck |
| author_facet | Luc Deroche Albane Rozenholc François Arrivé Jean-Philippe Martellosio Gwenaël Le Moal Arnaud W. Thille Olivier Barraud Sandrine Marchand Julien M. Buyck |
| author_sort | Luc Deroche |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-23f8582a785743c08b5269b68dbac8a0 |
| institution | Kabale University |
| issn | 1201-9712 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Infectious Diseases |
| spelling | doaj-art-23f8582a785743c08b5269b68dbac8a02024-12-18T08:47:35ZengElsevierInternational Journal of Infectious Diseases1201-97122025-02-01151107321Emergence of cefiderocol resistance during therapy in NDM-5–producing Klebsiella pneumoniae isolates harboring siderophore receptors mutationsLuc Deroche0Albane Rozenholc1François Arrivé2Jean-Philippe Martellosio3Gwenaël Le Moal4Arnaud W. Thille5Olivier Barraud6Sandrine Marchand7Julien M. Buyck8Université de Poitiers, PHAR2, Inserm U1070, Poitiers, France; CHU de Poitiers, Département des agents infectieux, Poitiers, FranceUniversité de Poitiers, PHAR2, Inserm U1070, Poitiers, FranceCHU de Poitiers, Service de Médecine Intensive - Réanimation, Poitiers, FranceCHU de Poitiers, Service de Médecine Interne, maladies infectieuses et tropicales, Poitiers, FranceCHU de Poitiers, Service de Médecine Interne, maladies infectieuses et tropicales, Poitiers, FranceCHU de Poitiers, Service de Médecine Intensive - Réanimation, Poitiers, FranceUniversité Limoges, INSERM, CHU Limoges, UMR 1092, Limoges, France; Clinical Investigation Center CIC1435, CHU Limoges, Limoges, FranceUniversité de Poitiers, PHAR2, Inserm U1070, Poitiers, France; CHU de Poitiers, Laboratoire de Toxicologie et de Pharmacocinétique, Poitiers, FranceUniversité de Poitiers, PHAR2, Inserm U1070, Poitiers, France; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S1201971224003965CefiderocolAntibiotic resistanceKlebsiella pneumoniaeSiderophore receptorWGS |
| spellingShingle | Luc Deroche Albane Rozenholc François Arrivé Jean-Philippe Martellosio Gwenaël Le Moal Arnaud W. Thille Olivier Barraud Sandrine Marchand Julien M. Buyck Emergence of cefiderocol resistance during therapy in NDM-5–producing Klebsiella pneumoniae isolates harboring siderophore receptors mutations International Journal of Infectious Diseases Cefiderocol Antibiotic resistance Klebsiella pneumoniae Siderophore receptor WGS |
| title | Emergence of cefiderocol resistance during therapy in NDM-5–producing Klebsiella pneumoniae isolates harboring siderophore receptors mutations |
| title_full | Emergence of cefiderocol resistance during therapy in NDM-5–producing Klebsiella pneumoniae isolates harboring siderophore receptors mutations |
| title_fullStr | Emergence of cefiderocol resistance during therapy in NDM-5–producing Klebsiella pneumoniae isolates harboring siderophore receptors mutations |
| title_full_unstemmed | Emergence of cefiderocol resistance during therapy in NDM-5–producing Klebsiella pneumoniae isolates harboring siderophore receptors mutations |
| title_short | Emergence of cefiderocol resistance during therapy in NDM-5–producing Klebsiella pneumoniae isolates harboring siderophore receptors mutations |
| title_sort | emergence of cefiderocol resistance during therapy in ndm 5 producing klebsiella pneumoniae isolates harboring siderophore receptors mutations |
| topic | Cefiderocol Antibiotic resistance Klebsiella pneumoniae Siderophore receptor WGS |
| url | http://www.sciencedirect.com/science/article/pii/S1201971224003965 |
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