Diversity of carbapenemase-producing Enterobacterales in England as revealed by whole-genome sequencing of isolates referred to a national reference laboratory over a 30-month period

Introduction. Increasing numbers of carbapenemase-producing Enterobacterales (CPE), which can be challenging to treat, have been referred to the national reference laboratory in England since the early 2000s. Gap Statement/Aim. Previous studies on CPE in the UK have focussed on localized outbreaks. We applied whole-genome sequencing (WGS) to isolates referred to the national reference laboratory over 30 months to inform our understanding of CPE epidemiology in England. Methodology. The first confirmed CPE from each new patient referred by an English diagnostic laboratory between 1 January 2014 and 30 June 2016 was sequenced on an Illumina HiSeq 2500. Multiple isolates from the same patient were included from either different species or the same species with different carbapenemase genes. The data were analysed using an in-house bioinformatics pipeline that determines species identification, multi-locus sequence typing (MLST) profile and antimicrobial resistance gene content. Results. A total of 2658 non-duplicate CPE were sequenced amongst which three host organisms belonging to diverse sequence types (STs) predominated: Klebsiella pneumoniae (1380/2658, 51.9%; 177 STs), Escherichia coli (723/2658, 27.2%; 133 STs) and Enterobacter cloacae (294/2658, 11.1%; 88 STs). Thirty different carbapenemase gene variants were identified, although bla_OXA-48-like (1122/2658, 42.2%), bla_NDM (692/2658, 26.0%), bla_KPC (571/2658, 21.5%), bla_VIM (100/2658, 3.8%) and bla_IMP (33/2658, 1.2%) predominated. ST/carbapenemase gene pairings represented widely distributed high-risk clones or clusters at a regional or hospital level. Conclusion. CPE referred to the national reference laboratory are diverse, suggesting multiple introductions to England and a role for horizontal transfer of carbapenemase genes in English CPE epidemiology.