[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]
Phenotypic, biochemical and genetic analysis of KPC-41, a KPC-3 variant conferring resistance to ceftazidime-avibactam and exhibiting reduced carbapenemase activity
Linda Mueller, Amandine Masseron, Guy Prod’Hom, Tatiana Galperine, Gilbert Greub, Laurent Poirel, Patrice Nordmann
A novel KPC variant, KPC-41, was identified in a Klebsiella pneumoniae clinical isolate from Switzerland. This ß-lactamase possessed a three 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 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.
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Keywords: Antibiotics; Drugs Resistance; Klebsiella pneumoniae; Ceftazidime; Avibactam.