ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1543470
Identification of Two KPC Variants, KPC-204 and KPC-227, in ST11-K64 Klebsiella pneumoniae during Prolonged Hospitalization of a Single Patient
Provisionally accepted
- 1Department of Clinical Laboratory, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- 2Department of Geriatrics, First Hospital, Peking University, Beiing, Beijing Municipality, China
- 3Department of Clinical Laboratory, First Hospital, Peking University, Beijing, Beijing Municipality, China
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Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a critical global public health challenge due to its significant association with morbidity and mortality.Ceftazidime-avibactam (CZA) has emerged as an effective therapy against CRKP producing the serine carbapenemase KPC; however, resistance driven by novel KPC variants is increasingly reported. In this study, 27 CRKP isolates were collected from elderly pneumonia patients in China. Sequential isolates from a single patient undergoing prolonged hospitalization revealed dynamic resistance evolution. Wholegenome sequencing identified KPC-227, a novel KPC variant, alongside the previously reported KPC-204. KPC-204, carrying a "DDK" insertion at position 270, conferred resistance to both carbapenems and CZA, while KPC-227, harboring a D179Y mutation, restored carbapenem susceptibility but maintained CZA resistance. Molecular docking analyses revealed that the D179Y mutation impaired meropenem hydrolysis by decreasing binding affinity. Additionally, colistin resistance was observed due to a novel mgrB mutation. These findings highlight the high evolutionary potential of KPC enzymes and the importance of vigilance to curb the emergence and dissemination of resistance, which threatens the efficacy of critical last-resort antibiotics.Between November 2022 and February 2023, we collected carbapenem-resistant Klebsiella pneumoniae isolates from pneumonia patients (median age: 72 years; range: 65-89) with a history of ceftazidime-avibactam exposure in the geriatric ward of a tertiary hospital in northern China. A total of 27 CRKP isolates were obtained from 15
Keywords: KPC variants, Carbapenem resistance, Ceftazidime-avibactam resistance, Klebsiella pneumoniae, Antimicrobial susceptibility
Received: 11 Dec 2024; Accepted: 07 May 2025.
Copyright: © 2025 Sun, Zhou, Li, Sun, Qi, Liu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xinmin Liu, Department of Geriatrics, First Hospital, Peking University, Beiing, Beijing Municipality, China
Wanhai Wang, Department of Clinical Laboratory, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
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