KPC-39-Mediated Resistance to Ceftazidime-Avibactam in a Klebsiella pneumoniae ST307 Clinical Isolate
Agnès B. Jousset, Saoussen Oueslati, Cécile Emeraud, Rémy A. Bonnin, Laurent Dortet, Bogdan I. Iorga, Thierry Naas
Abstract
Resistance to the ceftazidime (CAZ)-avibactam (AVI) combination is increasingly being reported. Here, we report a CAZ-AVI-resistant Klebsiella pneumoniae strain belonging to the high-risk sequence type 307 (ST307) clone and producing Klebsiella pneumoniae carbapenemase 39 (KPC-39), a single-amino-acid variant of KPC-3 (A172T). Cloning experiments, steady-state kinetic parameters, and molecular dynamics simulations revealed a loss of carbapenemase activity and increased affinity for CAZ. KPC-39 was identified in a patient without prior exposure to CAZ-AVI, suggesting silent dissemination in European health care settings.
Topics & Concepts
Klebsiella pneumoniaeMicrobiologyclone (Java method)CeftazidimeBiologyKlebsiella infectionsEnterobacteriaceaeKlebsiellaCloning (programming)VirologyDrug resistanceBacteriaEscherichia coliStrain (injury)Antibiotic resistanceMolecular cloningPlasmidBacterial proteinGenotypeBeta-lactamSequence (biology)Antibacterial agentCross infectionAntibiotic Resistance in BacteriaMicrobial Natural Products and BiosynthesisBacterial Identification and Susceptibility Testing