A high-resolution genomic analysis of multidrug-resistant hospital outbreaks of Klebsiella pneumoniae

Hao Chung The, Abhilasha Karkey, Duy Pham Thanh, Christine J. Boinett, Amy K. Cain, Matthew Ellington, Kate S. Baker, Sabina Dongol, Corinne Thompson, Simon R. Harris, Thibaut Jombart, Tu Le Thi Phuong, Nhu Tran Do Hoang, Tuyen Ha Thanh, Shrijana Shretha, Suchita Joshi, Buddha Basnyat, Guy Thwaites, Nicholas R. Thomson, Maia A. RabaaStephen Baker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)
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Abstract

Multidrug-resistant (MDR) Klebsiella pneumoniae has become a leading cause of nosocomial infections worldwide. Despite itsprominence, little is known about the genetic diversity of K.pneumoniae in resource-poor hospital settings. Through whole-genome sequencing (WGS), we reconstructed an outbreak of MDR K.pneumoniae occurring on high-dependency wards in a hospital in Kathmandu during 2012 with a case-fatality rate of 75%. The WGS analysis permitted the identification of two MDR K.pneumoniae lineages causing distinct outbreaks within the complex endemic K.pneumoniae. Using phylogenetic reconstruction and lineage-specific PCR, our data predicted a scenario in which K.pneumoniae, circulating for 6months before the outbreak, underwent a series of ward-specific clonal expansions after the acquisition of genes facilitating virulence and MDR. We suggest that the early detection of a specific NDM-1 containing lineage in 2011 would have alerted the high-dependency ward staff to intervene. We argue that some form of real-time genetic characterisation, alongside clade-specific PCR during an outbreak, should be factored into future healthcare infection control practices in both high- and low-income settings.

Original languageEnglish
Pages (from-to)227-239
Number of pages13
JournalEMBO Molecular Medicine
Volume7
Issue number3
DOIs
Publication statusPublished - 1 Mar 2015
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2015. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • antimicrobial resistance
  • bloodstream infections
  • carbapenemases
  • Klebsiella pneumoniae
  • nosocomial infections

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