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EMBO Mol Med. 2015 Mar;7(3):227-39. doi: 10.15252/emmm.201404767.

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

Author information

1
The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
2
Patan Academy of Health Sciences, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Kathmandu, Nepal.
3
The Wellcome Trust Sanger Institute, Hinxton Cambridge, UK.
4
The Wellcome Trust Sanger Institute, Hinxton Cambridge, UK Addenbrooke's Hospital, Cambridge, UK.
5
The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK.
6
MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College, London, UK.
7
The Wellcome Trust Sanger Institute, Hinxton Cambridge, UK The London School of Hygiene and Tropical Medicine, London, UK.
8
The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, UK.
9
The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK The London School of Hygiene and Tropical Medicine, London, UK sbaker@oucru.org.

Abstract

Multidrug-resistant (MDR) Klebsiella pneumoniae has become a leading cause of nosocomial infections worldwide. Despite its prominence, 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 6 months 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.

KEYWORDS:

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

PMID:
25712531
PMCID:
PMC4364942
DOI:
10.15252/emmm.201404767
[Indexed for MEDLINE]
Free PMC Article

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