KPC-50 Confers Resistance to Ceftazidime-Avibactam Associated with Reduced Carbapenemase Activity

Laurent Poirel; Xavier Vuillemin; Mario Juhas; Amandine Masseron; Ursina Bechtel-Grosch; Simon Tiziani; Stefano Mancini; Patrice Nordmann

doi:10.1128/AAC.00321-20

KPC-50 Confers Resistance to Ceftazidime-Avibactam Associated with Reduced Carbapenemase Activity

Antimicrob Agents Chemother. 2020 Jul 22;64(8):e00321-20. doi: 10.1128/AAC.00321-20. Print 2020 Jul 22.

Authors

Laurent Poirel^{1

2

3}, Xavier Vuillemin⁴, Mario Juhas⁴, Amandine Masseron⁴, Ursina Bechtel-Grosch⁵, Simon Tiziani⁶, Stefano Mancini⁷, Patrice Nordmann^{4

2

3

8}

Affiliations

¹ Emerging Antibiotic Resistance Unit and Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland [email protected].
² Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Fribourg, Switzerland.
³ INSERM European Unit (IAME, France), University of Fribourg, Fribourg, Switzerland.
⁴ Emerging Antibiotic Resistance Unit and Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
⁵ Department of Trauma Surgery, University Hospital of Zürich, Zürich, Switzerland.
⁶ Institute of Intensive Medicine, University Hospital Zürich, University of Zürich, Zürich, Switzerland.
⁷ Institute of Medical Microbiology, University of Zürich, Zürich, Switzerland.
⁸ Institut for Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland.

Abstract

KPC-50 is a KPC-3 variant identified from a Klebsiella pneumoniae clinical isolate recovered in Switzerland in 2019. Compared to KPC-3, KPC-50 shows (i) a three-amino-acid insertion (Glu-Ala-Val) between amino acids 276 and 277, (ii) an increased affinity to ceftazidime, (iii) a decreased sensitivity to avibactam, explaining the ceftazidime-avibactam resistance, and (iv) an association with a sharp reduction of its carbapenemase activity.

Keywords: KPC; Klebsiella pneumoniae; ceftazidime-avibactam.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology
Azabicyclo Compounds / pharmacology
Bacterial Proteins / genetics
Ceftazidime* / pharmacology
Drug Combinations
Drug Resistance, Bacterial
Humans
Klebsiella Infections* / drug therapy
Klebsiella pneumoniae / genetics
Microbial Sensitivity Tests
Switzerland
beta-Lactamases / genetics

Substances

Anti-Bacterial Agents
Azabicyclo Compounds
Bacterial Proteins
Drug Combinations
avibactam, ceftazidime drug combination
Ceftazidime
beta-Lactamases
carbapenemase