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

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 similar to 50, similar to 62 or similar to 85 kb plasmids. The plasmids and chromosomal insertswere 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 blaOXA-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.