Major role of pKpQIL-like plasmids in the early dissemination of KPC-type carbapenemases in the UK

Objectives: KPC-producing Enterobacteriaceae were first seen in the UK in 2003 and have been increasingly reported since 2010, largely owing to an ongoing outbreak in North-West England. We examined the role of clonal spread and plasmid transmission in their emergence.

Methods: Isolates comprised KPC-positive Klebsiella pneumoniae (n=33), Escherichia coli (n=7) and Enterobacter spp. (n=4) referred to the national reference laboratory between 2008 and 2010 from 17 UK centres, including three in North-West England. Isolates were typed by MLST. Plasmids were transferred by electroporation and characterised by PCR or sequencing. PCR screening assays were developed to distinguish plasmid pKpQIL variants.

Results: The K. pneumoniae isolates included 10 STs, of which three belonged to clonal group (CG) 258. CG258 (n=19) isolates were detected in 13 centres but accounted for only 7/19 (36.8%) of those from North-West England. Most KPC-producers (37/44, 84.1%), including 16/19 CG258 K. pneumoniae carried blaKPC on IncFIIK2 plasmids. Sequencing of a subset of these plasmids (n=11) revealed similarities with published pKpQIL. One variant, pKpQIL-UK - identified in K. pneumoniae CG258 (n=5) and ST468 (n=1) isolates from distinct centres - had only a few nucleotide changes from classical pKpQIL, whereas pKpQIL-D1 (n=1) and pKpQIL-D2 (n=4), from isolates of various species in the North-West, harboured large variations reflecting replacement of the partitioning and replication functions and potentially thereby facilitating spread. PCR revealed that 36/37 (97.3%) IncFIIK2-type plasmids in KPC-positive isolates had pKpQIL markers.

Conclusions: pKpQIL-like plasmids played a major role in the early dissemination of KPC enzymes in the UK.