@article{3b045385578a4ce9bcf088886b453f93,
title = "Genomic dissection of Klebsiella pneumoniae infections in hospital patients reveals insights into an opportunistic pathogen",
abstract = "Klebsiella pneumoniae is a major cause of opportunistic healthcare-associated infections, which are increasingly complicated by the presence of extended-spectrum beta-lactamases (ESBLs) and carbapenem resistance. We conducted a year-long prospective surveillance study of K. pneumoniae clinical isolates in hospital patients. Whole-genome sequence (WGS) data reveals a diverse pathogen population, including other species within the K. pneumoniae species complex (18%). Several infections were caused by K. variicola/K. pneumoniae hybrids, one of which shows evidence of nosocomial transmission. A wide range of antimicrobial resistance (AMR) phenotypes are observed, and diverse genetic mechanisms identified (mainly plasmid-borne genes). ESBLs are correlated with presence of other acquired AMR genes (median n = 10). Bacterial genomic features associated with nosocomial onset are ESBLs (OR 2.34, p = 0.015) and rhamnose-positive capsules (OR 3.12, p < 0.001). Virulence plasmid-encoded features (aerobactin, hypermucoidy) are observed at low-prevalence (<3%), mostly in community-onset cases. WGS-confirmed nosocomial transmission is implicated in just 10% of cases, but strongly associated with ESBLs (OR 21, p < 1 × 10−11). We estimate 28% risk of onward nosocomial transmission for ESBL-positive strains vs 1.7% for ESBL-negative strains. These data indicate that K. pneumoniae infections in hospitalised patients are due largely to opportunistic infections with diverse strains, with an additional burden from nosocomially-transmitted AMR strains and community-acquired hypervirulent strains.",
author = "Gorrie, {Claire L.} and Mirjana Mir{\v c}eta and Wick, {Ryan R.} and Judd, {Louise M.} and Lam, {Margaret M.C.} and Ryota Gomi and Abbott, {Iain J.} and Thomson, {Nicholas R.} and Strugnell, {Richard A.} and Pratt, {Nigel F.} and Garlick, {Jill S.} and Watson, {Kerrie M.} and Hunter, {Peter C.} and Pilcher, {David V.} and McGloughlin, {Steve A.} and Spelman, {Denis W.} and Wyres, {Kelly L.} and Jenney, {Adam W.J.} and Holt, {Kathryn E.}",
note = "Funding Information: This work was supported by the National Health and Medical Research Council of Australia (Project 1043822 and Fellowship 1061409 to K.E.H.), the Australian Government Research Training Program (Scholarship to C.L.G.), the Viertel Foundation of Australia (Senior Medical Research Fellowship to K.E.H.), the Wellcome Sanger Institute (Grant 098051), and the Bill and Melinda Gates Foundation, Seattle (OPP1175797 to K.E.H.). Under the grant conditions of the latter Foundation and the Wellcome Trust, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version. The funding bodies had no role in study design or in data collection, analysis and interpretation. The authors gratefully acknowledge the contribution and support of Janine Roney, Mellissa Bryant, Jennifer Williams and Noelene Browne at the Alfred Hospital; Elke van Gorp of Monash University for re-testing fosfomycin susceptibility of selected isolates; and the sequencing team at the Wellcome Sanger Institute. We also thank the team of curators at the Institut Pasteur MLST system (Paris, France) for importing novel alleles, profiles and/or isolates at http://bigsdb.web.pasteur.fr. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-30717-6",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}