Carbapenemase and virulence factors of Enterobacteriaceae in North Lebanon between 2008 and 2012: evolution via endemic spread of OXA-48

J Antimicrob Chemother. 2014 Oct;69(10):2699-705. doi: 10.1093/jac/dku181. Epub 2014 Jun 5.

Abstract

Objectives: To investigate the resistance to carbapenems in Enterobacteriaceae and the underlying resistance mechanisms in North Lebanon between 2008 and 2012.

Methods: A total of 2767 Enterobacteriaceae isolates recovered from clinical samples collected in Nini Hospital (North Lebanon) were screened for a decrease in susceptibility or resistance to ertapenem (MIC >0.25 mg/L). Enterobacteriaceae were similarly screened from 183 faecal samples obtained from non-hospitalized patients. The bacterial isolates were assigned to clonal lineages by PFGE and multilocus sequence typing. Carbapenemase genes, their genetic environment and virulence genes were characterized by molecular approaches.

Results: The rate of Enterobacteriaceae exhibiting a decrease in susceptibility or resistance to ertapenem increased from 0.4% in 2008-10 to 1.6% in 2012 for the clinical isolates recovered from hospitalized patients. Of these isolates, scattered among seven enterobacterial species, 88% produced OXA-48 carbapenemase. However, Escherichia coli represented 73% of the OXA-48-producing Enterobacteriaceae collected in 2012 at this hospital. During the faecal carriage study performed in non-hospitalized patients, E. coli was the only species producing OXA-48. The bla(OXA-48) gene was mainly found within Tn1999.2-type transposons inserted into E. coli chromosomes or in ∼50, ∼62 or ∼85 kb plasmids. The plasmids and chromosomal inserts were related to pOXA-48a. Molecular typing of the isolates revealed clonal diversity of E. coli and Klebsiella pneumoniae producing OXA-48. OXA-48 was observed in all major E. coli phylogroups, including D and B2, and isolates harbouring virulence genes of extra-intestinal pathogenic E. coli. Although not belonging to highly virulent capsular genotypes, the OXA-48-producing K. pneumoniae harboured genes associated with virulence or host colonization.

Conclusions: Horizontal transfer of related plasmids has facilitated the spread of the bla(OXA-48) gene into several Enterobacteriaceae species, including virulent E. coli. Their clonal diversity and the presence of faecal carriers in the community suggest an endemic spread of OXA-48.

Keywords: Escherichia coli; Klebsiella pneumoniae; OXA-48.

Publication types

  • Historical Article
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics*
  • Chromosome Mapping
  • Chromosomes, Bacterial
  • Cross Infection
  • Drug Resistance, Bacterial / genetics
  • Enterobacteriaceae / classification
  • Enterobacteriaceae / drug effects
  • Enterobacteriaceae / genetics*
  • Enterobacteriaceae / isolation & purification
  • Enterobacteriaceae Infections / epidemiology*
  • Enterobacteriaceae Infections / history
  • Enterobacteriaceae Infections / microbiology*
  • Genes, Bacterial
  • History, 21st Century
  • Humans
  • Lebanon / epidemiology
  • Microbial Sensitivity Tests
  • Multilocus Sequence Typing
  • Phenotype
  • Plasmids / genetics
  • Virulence Factors / genetics
  • beta-Lactamases / genetics*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Virulence Factors
  • beta-Lactamases
  • carbapenemase