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. 2021 Nov 17;65(12):e0116021.
doi: 10.1128/AAC.01160-21. Epub 2021 Oct 4.

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

Agnès B Jousset  1   2   3   4 , Saoussen Oueslati  1   3 , Cécile Emeraud  1   2   3   4 , Rémy A Bonnin  1   2   3 , Laurent Dortet  1   2   3   4 , Bogdan I Iorga  5 , Thierry Naas  1   2   3   4
Affiliations

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

Agnès B Jousset et al. Antimicrob Agents Chemother. .

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.

Keywords: KPC; avibactam resistance; carbapenemase.

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Figures

FIG 1
FIG 1
KPC-39 conformations at the beginning (blue) and at the end (red) of the molecular dynamics simulation. Covalently bound CAZ (PDB code 2ZQD) is represented as magenta-colored sticks.
See this image and copyright information in PMC

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