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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
More...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 The global phylogenetic tree of ST11 CRKP revealed that subclone KL64 superseded subclone KL47 and exhibits a stronger intra-regional spreading characteristic.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
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