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Expansion and Transmission Dynamics of High-Risk Carbapenem-Resistant Klebsiella Pneumonia Subclones in China: An Epidemiological, Spatial, Genomic Analysis

40 Pages Posted: 6 Sep 2023

See all articles by Qi Wang

Qi Wang

Peking University - Department of Clinical Laboratory

Ruobing Wang

Peking University - Department of Clinical Laboratory

Shuyi Wang

Peking University - Institute of Medical Technology

Anru Zhang

Peking University - Department of Clinical Laboratory

Qiaoyan Duan

Peking University - Department of Clinical Laboratory

Shijun Sun

Peking University - Department of Clinical Laboratory

Longyang Jin

Peking University - Department of Clinical Laboratory

Xiaojuan Wang

Peking University - Department of Clinical Laboratory

Chunlei Wang

Government of the People's Republic of China - China-Japan Friendship Hospital

Haiquan Kang

Xuzhou Medical University

Zhijie Zhang

China Medical University

Kang Liao

Sun Yat-sen University (SYSU)

Yinghui Guo

Hebei Provincial Children's Hospital

Liang Jin

First Hospital of Qinhuangdao

Zhiwu Liu

Lanzhou University

Chunxia Yang

Capital Medical University - Beijing Chaoyang Hospital

Hui Wang

Peking University - Department of Clinical Laboratory

China Carbapenem-Resistant Enterobacterales (CRE) Network

Independent

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Abstract

Background: Carbapenem-resistant Klebsiella pneumonia (CRKP) is a global threat that varies across different regions. The global distribution, evolution, and clinical hazards of the predominantly prevalent ST11 CRKP clone are not well understood.

Methods: We performed a multicentre carbapenem-resistant Enterobacterales (CRE) molecular epidemiological study using polymerase chain reaction (PCR) and whole-genome sequencing (WGS) of samples obtained from 96 hospitals across 28 provinces and municipalities in China between 2011 and 2021. We integrated the sequences obtained from public databases and performed genetic epidemiology analysis of the ST11 CRKP clone.

Findings: CRKP comprised 71.4% of the 6609 non-repetitive CRE isolates and predominantly produced KPC-2 (81.0%). Among ST11 K. pneumoniae, KL64 serotypes exhibited considerable expansion; their proportion increased from 1.54% to 46.08% between 2011 and 2021. The global phylogenetic tree of ST11 CRKP revealed that subclone KL64 superseded subclone KL47 and exhibits a stronger intra-regional spreading characteristic. We inferred that ST11 CRKP emerged on the American continent in 1996 and subsequently advanced globally, with the major clones first emerging along the southeastern coast and gradually spreading inland in China by 2010. Bloodstream infections caused by strains from the last clade of KL64 lead to higher mortality rates (46.6%) in patients aged >65 years than the other clades; these strains exhibit enhanced resistance to phagocytosis and greater in vitro competitive advantage than those in the remaining clades. Comparison of phylogenetic trees and SNPs revealed that over 99% of KL64 strains harbour mutations in genes related to antimicrobial resistance (bmr3 and oprD), virulence (efeO), and metabolism (yifK, recC, yicJ, mltC, ppsC, pyrB, and sdaC1), which may account for the dynamics of KL64 subclone expansion.

Interpretation: The high-risk subclone KL64-ST11-CRKP exhibits a notable propensity for expansion and possesses a distinct phenotypic advantage. Multiple genetic factors may be associated with the high prevalence of KL64-ST11-CRKP.

Funding: This study was partly supported by the National Natural Science Foundation of China (Grant No. 81991533 and No. 32141001).

Declaration of Interest: The authors report that there are no competing interests to declare.

Ethical Approval: The study was reviewed and approved by the Ethical Review Committee of Peking University People’s Hospital (2018PHB248-01).

Keywords: carbapenem-resistant Klebsiella pneumonia, subclone replacement, transmission dynamics, population expansion, intra-regional spread

Suggested Citation

Wang, Qi and Wang, Ruobing and Wang, Shuyi and Zhang, Anru and Duan, Qiaoyan and Sun, Shijun and Jin, Longyang and Wang, Xiaojuan and Wang, Chunlei and Kang, Haiquan and Zhang, Zhijie and Liao, Kang and Guo, Yinghui and Jin, Liang and Liu, Zhiwu and Yang, Chunxia and Wang, Hui and Network, China Carbapenem-Resistant Enterobacterales (CRE), Expansion and Transmission Dynamics of High-Risk Carbapenem-Resistant Klebsiella Pneumonia Subclones in China: An Epidemiological, Spatial, Genomic Analysis. Available at SSRN: https://ssrn.com/abstract=4560973 or http://dx.doi.org/10.2139/ssrn.4560973

Qi Wang

Peking University - Department of Clinical Laboratory ( email )

Ruobing Wang

Peking University - Department of Clinical Laboratory ( email )

Shuyi Wang

Peking University - Institute of Medical Technology ( email )

Anru Zhang

Peking University - Department of Clinical Laboratory ( email )

Qiaoyan Duan

Peking University - Department of Clinical Laboratory ( email )

Shijun Sun

Peking University - Department of Clinical Laboratory ( email )

Longyang Jin

Peking University - Department of Clinical Laboratory

Xiaojuan Wang

Peking University - Department of Clinical Laboratory ( email )

Chunlei Wang

Government of the People's Republic of China - China-Japan Friendship Hospital ( email )

China

Haiquan Kang

Xuzhou Medical University ( email )

Zhijie Zhang

China Medical University ( email )

Kang Liao

Sun Yat-sen University (SYSU) ( email )

Yinghui Guo

Hebei Provincial Children's Hospital ( email )

Liang Jin

First Hospital of Qinhuangdao ( email )

China

Zhiwu Liu

Lanzhou University ( email )

Chunxia Yang

Capital Medical University - Beijing Chaoyang Hospital ( email )

Beijing
China

Hui Wang (Contact Author)

Peking University - Department of Clinical Laboratory ( email )

Beijing
China

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