ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Molecular Bacterial Pathogenesis
This article is part of the Research TopicNew Insights on Microbial Virulence Factors, Resistance, and Novel Therapeutic StrategiesView all articles
Molecular epidemiology of carbapenem-resistant hypervirulent Klebsiella pneumoniae: Risk factors and resistance mechanism of ceftazidime/avibactam in China
Provisionally accepted
Na Wang
Lexiu DengHuiying LiNa Jia
Xiaocui Peng
Jianliang ChangJiatong HaoJianhua TangChunmei Lei
Bu Wang*Jianhua Liu*
Zhang Wei*- First Affiliated Hospital of Hebei North University, Zhangjiakou, China
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Background: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) represents a critical public health threat in China, characterized by the convergence of multidrug resistance and hypervirulence. The emergence of ceftazidime/avibactam (CZA) resistance further complicates clinical management. This study aimed to elucidate the molecular epidemiology, risk factors, and resistance mechanisms of CZA resistance in CR-hvKP across China, providing evidence for targeted interventions. Methods: A single-center molecular epidemiological analysis was conducted on 81 Carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical isolates collected. All isolates underwent whole-genome sequencing for MultiLocus Sequence Typing, capsule typing, and identification of resistance genes (blaKPC-2 and blaNDM-1) and virulence factors (iucA, iroB, rmpA, rmpA2, and peg-344). CZA resistance mechanisms were investigated through broth microdilution minimum inhibitory concentration (MIC) testing and bioinformatics analysis. Galleria mellonella infection models were employed to assess virulence potential. Risk factors were analyzed using multivariate regression of clinical variables. Phylogenetic reconstruction employed single-nucleotide polymorphism-based analysis. Results: ST11 accounted for 96.15% (50/52) of CR-hvKP isolates, with K64 being the predominant capsule type (92.31%, 48/52). Additionally, 98.77% (80/81) of CRKP carried ≥1 virulence gene; 64.2% (52/81) of isolates with all five virulence genes exhibited lethality. Galleria mellonella revealed that the survival rate of CR-hvKP was lower than that of carbapenem-resistant non-hypervirulent Klebsiella pneumoniae (p<0.05). Antibiotic usage time (odds ratio [OR]=1.076, 95% confidence interval [CI]: 1.026–1.138), carbapenem antibiotic (OR=0.117, 95% CI: 0.02266–0.4602), and malignant tumors (OR=65.1, 95% CI: 7.078–1798) predicted CR-hvKP infection. Transferable blaKPC-2 on IncFII/IncR plasmids conferred CZA resistance (MIC>128 mg/L) without compromising carbapenem resistance, facilitated by a unique genetic context (TnpR_Tn3-ISKpn27-blaKPC-2-ISKpn6). Conclusion: China faces a rapid dissemination of ST11 CR-hvKP clones carrying diversified CZA resistance mechanisms. The convergence of hypervirulence and resistance in ST11 lineages— accelerated by invasive procedures and international transmission—demands enhanced genomic surveillance. CZA resistance arises through multiple pathways, necessitating combination therapies and stewardship programs limiting prolonged CZA use. Our findings underscore an urgent need for rapid diagnostics targeting emergent resistance determinants and infection control measures to contain high-risk clones.
Keywords: carbapenem-resistant hypervirulent Klebsiella pneumoniae, Ceftazidime-avibactam resistance, ST11 clone, Molecular Epidemiology, China
Received: 03 Sep 2025; Accepted: 26 Nov 2025.
Copyright: © 2025 Wang, Deng, Li, Jia, Peng, Chang, Hao, Tang, Lei, Wang, Liu and Wei. 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:
Bu Wang
Jianhua Liu
Zhang Wei
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