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KPC-39-Mediated Resistance to Ceftazidime-Avibactam in a Klebsiella Pneumoniae ST307 Clinical Isolate

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Specialty Pharmacology
Date 2021 Oct 4
PMID 34606331
Citations 13
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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.

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