Evolution and Transmission of Carbapenem-Resistant Klebsiella pneumoniae Expressing the blaOXA-232 Gene During an Institutional Outbreak Associated With Endoscopic Retrograde Cholangiopancreatography

Clin Infect Dis. 2017 Apr 1;64(7):894-901. doi: 10.1093/cid/ciw876.

Abstract

Background: Whole-genome sequencing (WGS) is an emerging and powerful technique by which to perform epidemiological studies in outbreak situations.

Methods: WGS was used to identify and evaluate an outbreak of OXA-232-expressing carbapenem-resistant Klebsiella pneumoniae (CRKP) transmitted to 16 patients over the course of 40 weeks via endoscopic retrograde cholangiopancreatography procedures at a single institution. WGS was performed on 32 OXA-232 CRKP isolates (1-7 per patient) and single-nucleotide variants (SNVs) were analyzed, with reference to the index patient's isolate.

Results: Interhost genetic diversity of isolates was between 0 and 15 SNVs during the outbreak; molecular clock calculations estimated 12.31 substitutions per genome per year (95% credibility interval, 7.81-17.05). Both intra- and interpatient diversification at the plasmid and transposon level was observed, significantly impacting the antibiogram of outbreak isolates. The majority of isolates evaluated (n = 27) harbored a blaCTX-M-15 gene, but some (n = 5) lacked the transposon carrying this gene, which resulted in susceptibility to aztreonam and third- and fourth-generation cephalosporins. Similarly, an isolate from a colonized patient lacked the transposon carrying rmtF and aac(6')lb genes, resulting in susceptibility to aminoglycosides.

Conclusions: This study broadens the understanding of how bacteria diversify at the genomic level over the course of a defined outbreak and provides reference for future outbreak investigations.

Keywords: CRE outbreak; ERCP; OXA-232; carbapenem-resistant Klebsiella pneumoniae.; whole-genome sequencing.

MeSH terms

  • Carbapenems / pharmacology*
  • Cholangiopancreatography, Endoscopic Retrograde / adverse effects*
  • Cross Infection
  • Disease Outbreaks
  • Enzyme Activation
  • Genetic Variation
  • Genome, Bacterial
  • Humans
  • Klebsiella Infections / epidemiology*
  • Klebsiella Infections / transmission*
  • Klebsiella pneumoniae / classification
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / genetics*
  • Phylogeny
  • Plasmids / genetics
  • Whole Genome Sequencing
  • beta-Lactamases / genetics*
  • beta-Lactamases / metabolism

Substances

  • Carbapenems
  • beta-Lactamases