A Prolonged Outbreak of KPC-3-Producing Enterobacter cloacae and Klebsiella pneumoniae Driven by Multiple Mechanisms of Resistance Transmission at a Large Academic Burn Center

Antimicrob Agents Chemother. 2017 Jan 24;61(2):e01516-16. doi: 10.1128/AAC.01516-16. Print 2017 Feb.

Abstract

Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacter cloacae has been recently recognized in the United States. Whole-genome sequencing (WGS) has become a useful tool for analysis of outbreaks and for determining transmission networks of multidrug-resistant organisms in health care settings, including carbapenem-resistant Enterobacteriaceae (CRE). We experienced a prolonged outbreak of CRE E. cloacae and K. pneumoniae over a 3-year period at a large academic burn center despite rigorous infection control measures. To understand the molecular mechanisms that sustained this outbreak, we investigated the CRE outbreak isolates by using WGS. Twenty-two clinical isolates of CRE, including E. cloacae (n = 15) and K. pneumoniae (n = 7), were sequenced and analyzed genetically. WGS revealed that this outbreak, which seemed epidemiologically unlinked, was in fact genetically linked over a prolonged period. Multiple mechanisms were found to account for the ongoing outbreak of KPC-3-producing E. cloacae and K. pneumoniae This outbreak was primarily maintained by a clonal expansion of E. cloacae sequence type 114 (ST114) with distribution of multiple resistance determinants. Plasmid and transposon analyses suggested that the majority of blaKPC-3 was transmitted via an identical Tn4401b element on part of a common plasmid. WGS analysis demonstrated complex transmission dynamics within the burn center at levels of the strain and/or plasmid in association with a transposon, highlighting the versatility of KPC-producing Enterobacteriaceae in their ability to utilize multiple modes to resistance gene propagation.

Keywords: Klebsiella pneumoniae carbapenemase (KPC); burn patients; carbapenem-resistant Enterobacteriaceae (CRE); health care-associated infection; outbreak; whole-genome sequencing.

MeSH terms

  • Adult
  • Aged
  • Bacterial Proteins / genetics
  • Burn Units
  • Disease Outbreaks
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Enterobacter cloacae / drug effects*
  • Enterobacter cloacae / genetics
  • Enterobacter cloacae / pathogenicity
  • Enterobacteriaceae Infections / drug therapy
  • Enterobacteriaceae Infections / epidemiology
  • Enterobacteriaceae Infections / microbiology*
  • Female
  • Genome, Bacterial
  • Humans
  • Klebsiella Infections / drug therapy
  • Klebsiella Infections / epidemiology
  • Klebsiella Infections / microbiology*
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / genetics
  • Klebsiella pneumoniae / pathogenicity
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • North Carolina / epidemiology
  • beta-Lactamases / genetics

Substances

  • Bacterial Proteins
  • beta-Lactamases
  • beta-lactamase KPC-3, Enterobacter cloacae
  • beta-lactamase KPC-3, Klebsiella pneumoniae