A High-Resolution Genomic Analysis of Multidrug-Resistant Hospital Outbreaks of Klebsiella Pneumoniae

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cluster Analysis
  • Cross Infection / epidemiology*
  • Cross Infection / microbiology
  • Disease Outbreaks*
  • Drug Resistance, Multiple, Bacterial*
  • Evolution, Molecular
  • Genes, Bacterial
  • Genome, Bacterial
  • Genomics
  • Genotype
  • Humans
  • Infection Control / methods
  • Klebsiella Infections / epidemiology*
  • Klebsiella Infections / microbiology
  • Klebsiella pneumoniae / classification*
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / genetics*
  • Klebsiella pneumoniae / isolation & purification
  • Mice
  • Molecular Sequence Data
  • Nepal / epidemiology
  • Phylogeny
  • Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Sequence Homology
  • Virulence Factors / genetics

Substances

  • Virulence Factors

Associated data

  • GENBANK/CDQG01000001
  • GENBANK/LN714331