Phenotypic, biochemical, and genetic analysis of kpc-41, a kpc-3 variant conferring resistance to ceftazidime-avibactam and exhibiting reduced carbapenemase activity
- Mueller, Linda Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Switzerland - Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Switzerland - Institut for Microbiology, University Hospital Center and University of Lausanne, Switzerland
- Masseron, Amandine Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Switzerland
- Prod’Hom, Guy Institut for Microbiology, University Hospital Center and University of Lausanne, Switzerland
- Galperine, Tatiana Infectiology Department, University Hospital Center and University of Lausanne, Switzerland
- Greub, Gilbert Institut for Microbiology, University Hospital Center and University of Lausanne, Switzerland
- Poirel, Laurent Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Switzerland - Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Switzerland - INSERM European Unit (IAME, France), University of Fribourg, Switzerland
- Nordmann, Patrice Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Switzerland - Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Switzerland - Institut for Microbiology, University Hospital Center and University of Lausanne, Switzerland - INSERM European Unit (IAME, France), University of Fribourg, Switzerland
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01.12.2019
Published in:
- Antimicrobial Agents and Chemotherapy. - 2019, vol. 63, no. 12, p. 10.1128/aac.01111-19
English
A novel KPC variant, KPC-41, was identified in a Klebsiella pneumoniae clinical isolate from Switzerland. This β-lactamase possessed a 3-amino-acid insertion (Pro- Asn-Lys) located between amino acids 269 and 270 compared to the KPC-3 amino acid sequence. Cloning and expression of the blaKPC-41 gene in Escherichia coli, followed by determination of MIC values and kinetic parameters, showed that KPC-41, compared to those of KPC-3, has an increased affinity to ceftazidime and a decreased sensitivity to avibactam, leading to resistance to ceftazidime-avibactam once produced in K. pneumoniae. Furthermore, KPC-41 exhibited a drastic decrease of its carbapenemase activity. This report highlights that a diversity of KPC variants conferring resistance to ceftazidime-avibactam already circulate in Europe.
- Faculty
- Faculté des sciences et de médecine
- Department
- Médecine 3ème année
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 327731
- DOI 10.1128/AAC.01111-19
- Persistent URL
- https://folia.unifr.ch/unifr/documents/308401
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