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dc.contributor.authorWyres, Kelly L.
dc.contributor.authorNguyen, To N. T.
dc.contributor.authorLam, Margaret M. C.
dc.contributor.authorJudd, Louise M.
dc.contributor.authorvan Vinh Chau, Nguyen
dc.contributor.authorDance, David A. B.
dc.contributor.authorIp, Margaret
dc.contributor.authorKarkey, Abhilasha
dc.contributor.authorLing, Clare L.
dc.contributor.authorMiliya, Thyl
dc.contributor.authorNewton, Paul N.
dc.contributor.authorLan, Nguyen Phu Huong
dc.contributor.authorSengduangphachanh, Amphone
dc.contributor.authorTurner, Paul
dc.contributor.authorVeeraraghavan, Balaji
dc.contributor.authorVinh, Phat Voong
dc.contributor.authorVongsouvath, Manivanh
dc.contributor.authorThomson, Nicholas R.
dc.contributor.authorBaker, Stephen
dc.contributor.authorHolt, Kathryn E.
dc.date.accessioned2021-01-15T16:14:47Z
dc.date.available2021-01-15T16:14:47Z
dc.date.issued2020-01-16
dc.date.submitted2019-07-26
dc.identifier.others13073-019-0706-y
dc.identifier.other706
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/316235
dc.description.abstractAbstract: 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.
dc.languageen
dc.publisherBioMed Central
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectResearch
dc.subjectKlebsiella pneumoniae
dc.subjectBloodstream infection
dc.subjectMDR
dc.subjectCapsule types
dc.subjectHypervirulent
dc.subjectGenomic surveillance
dc.titleGenomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia
dc.typeArticle
dc.date.updated2021-01-15T16:14:46Z
prism.issueIdentifier1
prism.publicationNameGenome Medicine
prism.volume12
dc.identifier.doi10.17863/CAM.63344
dcterms.dateAccepted2019-12-12
rioxxterms.versionofrecord10.1186/s13073-019-0706-y
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidBaker, Stephen [0000-0003-1308-5755]
dc.identifier.eissn1756-994X
pubs.funder-project-idWellcome Trust (#206194)
pubs.funder-project-idBill and Melinda Gates Foundation (OPP1175797)


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)