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Title: Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia
Authors: Kelly L. Wyres
To N.T. Nguyen
Margaret M.C. Lam
Louise M. Judd
Nguyen van Vinh Chau
David A.B. Dance
Margaret Ip
Abhilasha Karkey
Clare L. Ling
Thyl Miliya
Paul N. Newton
Nguyen Phu Huong Lan
Amphone Sengduangphachanh
Paul Turner
Balaji Veeraraghavan
Phat Voong Vinh
Manivanh Vongsouvath
Nicholas R. Thomson
Stephen Baker
Kathryn E. Holt
London School of Hygiene & Tropical Medicine
University of Cambridge
University of Oxford
Monash University
Mahidol University
Wellcome Sanger Institute
Chinese University of Hong Kong
Christian Medical College, Vellore
Mahosot Hospital
Oxford University Clinical Research Unit
Hospital of Tropical Diseases
Oxford University Clinical Research Unit
Angkor Hospital for Children
Keywords: Biochemistry, Genetics and Molecular Biology;Medicine
Issue Date: 16-Jan-2020
Citation: Genome medicine. Vol.12, No.1 (2020), 11
Abstract: BACKGROUND: Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extended-spectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies are urgently required, due to severely limited therapeutic options. South and Southeast Asia are major hubs for antimicrobial-resistant (AMR) K. pneumoniae and also for the characteristically antimicrobial-sensitive, community-acquired "hypervirulent" strains. The emergence of hypervirulent AMR strains and lack of data on exopolysaccharide diversity pose a challenge for K. pneumoniae BSI control strategies worldwide. METHODS: We conducted a retrospective genomic epidemiology study of 365 BSI K. pneumoniae from seven major healthcare facilities across South and Southeast Asia, extracting clinically relevant information (AMR, virulence, K and O antigen loci) using Kleborate, a K. pneumoniae-specific genomic typing tool. RESULTS: K. pneumoniae BSI isolates were highly diverse, comprising 120 multi-locus sequence types (STs) and 63 K-loci. ESBL and carbapenemase gene frequencies were 47% and 17%, respectively. The aerobactin synthesis locus (iuc), associated with hypervirulence, was detected in 28% of isolates. Importantly, 7% of isolates harboured iuc plus ESBL and/or carbapenemase genes. The latter represent genotypic AMR-virulence convergence, which is generally considered a rare phenomenon but was particularly common among South Asian BSI (17%). Of greatest concern, we identified seven novel plasmids carrying both iuc and AMR genes, raising the prospect of co-transfer of these phenotypes among K. pneumoniae. CONCLUSIONS: K. pneumoniae BSI in South and Southeast Asia are caused by different STs from those predominating in other regions, and with higher frequency of acquired virulence determinants. K. pneumoniae carrying both iuc and AMR genes were also detected at higher rates than have been reported elsewhere. The study demonstrates how genomics-based surveillance-reporting full molecular profiles including STs, AMR, virulence and serotype locus information-can help standardise comparisons between sites and identify regional differences in pathogen populations.
ISSN: 1756994X
Appears in Collections:Scopus 2020

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