Characterization of carbapenemase-producing Enterobacteriaceae in the West Midlands region of England: 2007-14

Objectives: Carbapenemase-producing Enterobacteriaceae (CPE) have been increasingly reported in the UK since 2003. We analysed patient and isolate data for CPE confirmed by the national reference laboratory from laboratories in the West Midlands region fromNovember 2007 to December 2014. Methods: MICs were determined by BSAC agar dilution methodology and isolates exhibiting resistance to one or more carbapenems were screened for carbapenemase genes by PCR. Plasmid analyses were performed after electro-transformation of carbapenemase-encoding plasmids. WGS was performed on both transformants and clinical isolates. Patient data provided by the sending laboratories were reviewed. Results: During the study period, CPE (n=139) were submitted from13 laboratories in the West Midlands region, originating from 108 patients and including one environmental isolate. CPE submissions increased significantly from 2009 onwards. Isolates were predominantly Klebsiella pneumoniae (89/139) obtained from inpatients. WGS was performed on all clinical isolates and transformants. After deduplication 119 isolates and 96 transformants remained for analysis. Within these, four families of carbapenemase genes were identified: bla_NDM (69/119), bla_KPC (26/119), bla_OXA-48-like (16/119) and bla_VIM (7/119); one isolate carried both bla_NDM and bla_{OXA-48- like}. Isolates represented diverse STs and plasmid replicon types. Plasmid analyses identified plasmids of different replicon types encoding bla_KPC, bla_NDM and bla_OXA-48-like genes, found across several species and STs. Conclusions: CPE have been reported increasingly in the West Midlands region over a 7 year period. bla_NDM, bla_KPC and bla_OXA-48-like were the dominant carbapenemase genes and were found in a range of diverse genomic/ plasmid environments, highlighting their ability to mobilize across different plasmids, often impeding the detection of outbreaks.