4.6 Article

Genomic Surveillance of Carbapenem-Resistant Klebsiella pneumoniae from a Major Public Health Hospital in Singapore

期刊

MICROBIOLOGY SPECTRUM
卷 -, 期 -, 页码 -

出版社

AMER SOC MICROBIOLOGY
DOI: 10.1128/spectrum.00957-22

关键词

carbapenem-resistant; Klebsiella pneumoniae; whole-genome sequencing; drug resistance mechanisms; plasmid-mediated resistance; virulence factors

资金

  1. National Medical Research Council, Singapore [NMRC/CG/C005/2017, NMRC/MOH-000018-00, NMRC/CG21APR2005, NMRC/CG21APR1011]
  2. Saw Swee Hock School of Public Health Infectious Diseases Program [SSHSPH ID-PRG/SeedFund/2018/05]
  3. NUS Start-Up Grant

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In this study, carbapenem-resistant Klebsiella pneumoniae clinical isolates collected from the largest public acute-care hospital in Singapore over a 12-year period were characterized using whole-genome sequencing. The study revealed significant genomic diversity, with the presence of both epidemic, multidrug-resistant clones and diverse nonepidemic lineages.
In this study, we characterized carbapenem-resistant Klebsiella pneumoniae clinical isolates collected over a 12-year period in the largest public acute-care hospital in Singapore using whole-genome sequencing. The results of this study demonstrate significant genomic diversity with the presence of well-known epidemic, multidrug-resistant clones amid a diverse pool of nonepidemic lineages. Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global public health threat. In this study, we employed whole-genome sequencing (WGS) to determine the genomic epidemiology of a longitudinal collection of clinical CRKP isolates recovered from a large public acute care hospital in Singapore. Phylogenetic analyses, a characterization of resistance and virulence determinants, and plasmid profiling were performed for 575 unique CRKP isolates collected between 2009 and 2020. The phylogenetic analyses identified the presence of global high-risk clones among the CRKP population (clonal group [CG] 14/15, CG17/20, CG147, CG258, and sequence type [ST] 231), and these clones constituted 50% of the isolates. Carbapenemase production was common (n = 497, 86.4%), and KPC was the predominant carbapenemase (n = 235, 40.9%), followed by OXA-48-like (n = 128, 22.3%) and NDM (n = 93, 16.2%). Hypervirulence was detected in 59 (10.3%) isolates and was most common in the ST231 carbapenemase-producing isolates (21/59, 35.6%). Carbapenemase genes were associated with diverse plasmid replicons; however, there was an association of bla(OXA-181/232) with ColKP3 plasmids. This study presents the complex and diverse epidemiology of the CRKP strains circulating in Singapore. Our study highlights the utility of WGS-based genomic surveillance in tracking the population dynamics of CRKP. IMPORTANCE In this study, we characterized carbapenem-resistant Klebsiella pneumoniae clinical isolates collected over a 12-year period in the largest public acute-care hospital in Singapore using whole-genome sequencing. The results of this study demonstrate significant genomic diversity with the presence of well-known epidemic, multidrug-resistant clones amid a diverse pool of nonepidemic lineages. Genomic surveillance involving comprehensive resistance, virulence, and plasmid gene content profiling provided critical information for antimicrobial resistance monitoring and highlighted future surveillance priorities, such as the emergence of ST231 K. pneumoniae strains bearing multidrug resistance, virulence elements, and the potential plasmid-mediated transmission of the bla(OXA-48-like) gene. The findings here also reinforce the necessity of unique infection control and prevention strategies that take the genomic diversity of local circulating strains into consideration.

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