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Objectives: From 2012 to 2014, there has been a huge increase of Vancomycin resistant (vanA) Enterococcus faecium (VREfm) in the Capital Region of Denmark with 22 patients infected or colonised with VREfm in 2012 compared to 602 in 2014. The objective of the study was to describe the genetic epidemiology of VREfm to assess the contribution of clonal spread and horizontal transfer of the vanA transposon (Tn1546) and plasmid in the dissemination of VREfm in hospitals. Methods: VREfm from the Capital Region of Denmark, 2012 to 2014 were whole genome sequenced. The clonal structure was determined and the structure of Tn1546-like transposons was characterized. One VREfm isolate belonging to the largest clonal group was sequenced using long-read technology to close a 37 kbp vanA plasmid. Results: Phylogeny revealed a polyclonal structure where 495 VREfm isolates were divided into 13 main groups and 7 small groups. Three major groups (n=44, 100 and 218) were identified, and clonal spread of VREfm was identified between wards and hospitals. Five Tn1546-like transposon types were identified. The dominant Type 4 transposon (92%) was spread across all but one VREfm group. The closed vanA plasmid was highly covered by reads from isolates containing the Type 4 transposon. Conclusion: The study suggests that it was the dissemination of the Type 4 Tn1546-like transposon and plasmid via horizontal transfer to multiple populations of E. faecium, followed by clonal spread of new VREfm clones that contributed to the increase and diversity of VREfm in Danish hospitals. |