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.

Klebsiella pneumoniae is an opportunistic pathogen of increasing public health concern due to the prevalence of antimicrobial resistance. Here, the authors provide insight into the resistance profiles, bacterial genome features and virulence genes, in a year-long prospective study of K. pneumoniae clinical isolates.

Details

Title
Genomic dissection of Klebsiella pneumoniae infections in hospital patients reveals insights into an opportunistic pathogen
Author
Gorrie, Claire L. 1   VIAFID ORCID Logo  ; Mirčeta, Mirjana 2 ; Wick, Ryan R. 3   VIAFID ORCID Logo  ; Judd, Louise M. 4 ; Lam, Margaret M. C. 3 ; Gomi, Ryota 5   VIAFID ORCID Logo  ; Abbott, Iain J. 6 ; Thomson, Nicholas R. 7   VIAFID ORCID Logo  ; Strugnell, Richard A. 1   VIAFID ORCID Logo  ; Pratt, Nigel F. 8 ; Garlick, Jill S. 8 ; Watson, Kerrie M. 3 ; Hunter, Peter C. 9 ; Pilcher, David V. 10 ; McGloughlin, Steve A. 10 ; Spelman, Denis W. 6 ; Wyres, Kelly L. 3   VIAFID ORCID Logo  ; Jenney, Adam W. J. 11 ; Holt, Kathryn E. 12   VIAFID ORCID Logo 

1  The University of Melbourne, Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
2  Microbiology Unit, Alfred Pathology Service, The Alfred Hospital, Melbourne, Australia (GRID:grid.1623.6) (ISNI:0000 0004 0432 511X) 
3  Monash University, Department of Infectious Diseases, Central Clinical School, Melbourne, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857) 
4  Monash University, Department of Infectious Diseases, Central Clinical School, Melbourne, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); The University of Melbourne, Doherty Applied Microbial Genomics (DAMG), Peter Doherty Institute for Infection and Immunity, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
5  Monash University, Department of Infectious Diseases, Central Clinical School, Melbourne, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); Kyoto University, Department of Environmental Engineering, Graduate School of Engineering, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
6  Microbiology Unit, Alfred Pathology Service, The Alfred Hospital, Melbourne, Australia (GRID:grid.1623.6) (ISNI:0000 0004 0432 511X); Monash University, Department of Infectious Diseases, Central Clinical School, Melbourne, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857) 
7  Wellcome Sanger Institute, Hinxton, UK (GRID:grid.10306.34) (ISNI:0000 0004 0606 5382); London School of Hygiene & Tropical Medicine, Department of Infection Biology, London, UK (GRID:grid.8991.9) (ISNI:0000 0004 0425 469X) 
8  Infectious Diseases Clinical Research Unit, The Alfred Hospital, Melbourne, Australia (GRID:grid.1623.6) (ISNI:0000 0004 0432 511X) 
9  Aged Care, Caulfield Hospital, Alfred Health, Melbourne, Australia (GRID:grid.267362.4) (ISNI:0000 0004 0432 5259) 
10  Intensive Care Unit, The Alfred Hospital, Melbourne, Australia (GRID:grid.1623.6) (ISNI:0000 0004 0432 511X); Monash University, Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventative Medicine, Melbourne, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857) 
11  The University of Melbourne, Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X); Microbiology Unit, Alfred Pathology Service, The Alfred Hospital, Melbourne, Australia (GRID:grid.1623.6) (ISNI:0000 0004 0432 511X); Monash University, Department of Infectious Diseases, Central Clinical School, Melbourne, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857) 
12  Monash University, Department of Infectious Diseases, Central Clinical School, Melbourne, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); London School of Hygiene & Tropical Medicine, Department of Infection Biology, London, UK (GRID:grid.8991.9) (ISNI:0000 0004 0425 469X) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-022-30717-6
ProQuest document ID
2671803097
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.