Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Identification of a Novel KPC Variant, KPC-204, Conferring Resistance to Both Carbapenems and Ceftazidime-Avibactam in an ST11 Klebsiella Pneumoniae Strain

Version 1 : Received: 16 May 2024 / Approved: 17 May 2024 / Online: 17 May 2024 (11:36:23 CEST)

How to cite: Gong, Y.; Feng, Y.; Lv, X. Identification of a Novel KPC Variant, KPC-204, Conferring Resistance to Both Carbapenems and Ceftazidime-Avibactam in an ST11 Klebsiella Pneumoniae Strain. Preprints 2024, 2024051139. https://doi.org/10.20944/preprints202405.1139.v1 Gong, Y.; Feng, Y.; Lv, X. Identification of a Novel KPC Variant, KPC-204, Conferring Resistance to Both Carbapenems and Ceftazidime-Avibactam in an ST11 Klebsiella Pneumoniae Strain. Preprints 2024, 2024051139. https://doi.org/10.20944/preprints202405.1139.v1

Abstract

This study describes KPC-204, a novel variant of Klebsiella Pneumoniae carbapenemase, characterized by a KDD amino acid insertion at Ambler position 269 deviates from KPC-2. This variant was identified in an ST11-type clinical isolate of carbapenem-resistant Klebsiella Pneumoniae from China. Notably, KPC-204 exhibits resistance to both ceftazidime-avibactam and carbapenems. Genetic analysis revealed that blaKPC-204 was located on a highly mobile IncFII/IncR plasmid within a complex genetic structure that facilitates its spread. Functional analysis, achieved through cloning into E. coli DH5α, validates KPC-204's contribution to increased resistance to ceftazidime-avibactam. The kinetic parameters showed that KPC-204 exhibited similar affinity to KPC-2 toward ceftazidime and reduced sensitivity to avibactam. Mating experiments demonstrated the resistance's transmissibility. This investigation underscores the evolving diversity of KPC variants affecting ceftazidime-avibactam resistance, highlighting the necessity for continuous monitoring.

Keywords

KPC-204; ceftazidime-avibactam; Klebsiella Pneumoniae

Subject

Medicine and Pharmacology, Epidemiology and Infectious Diseases

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