Characterization of enterobacteriaceae producing OXA-48-like carbapenemases in the UK

Objectives: To characterize UK clinical isolates of Enterobacteriaceae producing OXA-48-like carbapenemases and to compare their resistance plasmids.

Methods: Twenty-six enterobacteria producing OXA-48-like enzymes were studied. These were from 22 diverse hospitals in the UK. Isolates of Escherichia coli and Klebsiella pneumoniae were assigned to clonal lineages by multilocus sequence typing. Carbapenemase genes and their genetic environments were characterized by PCR and sequencing. Resistance plasmids were transferred by transformation or conjugation and compared by restriction analysis and PCR for genes encoding critical plasmid functions.

Results: Thirteen isolates of K. pneumoniae, 10 E. coli and 2 Enterobacter cloacae harboured a classical blaOXA-48 gene; the K. pneumoniae isolates belonged to 11 sequence types (STs) and the E. coli to 7 STs, including ST131 and ST38. The blaOXA-48 genes were located within either Tn1999 or Tn1999.2 transposons on related ∼50 kb or ∼62 kb plasmids, which lacked other resistance genes or, in one isolate, on an ∼140 kb plasmid that also encoded OXA-9 and CTX-M group-9 β-lactamases. One India-linked K. pneumoniae isolate had a blaOXA-181 gene in association with an ISEcp1 insertion sequence on a 7 kb plasmid.

Conclusions: Horizontal transfer of related plasmids has facilitated the spread of OXA-48 carbapenemase into multiple strains of several Enterobacteriaceae species. The clonal diversity of the producers suggests repeated introduction into the UK. Low carbapenem MICs for some producers complicates detection and creates a risk for unrecognized spread.