Consideration of within-patient diversity highlights transmission pathways and antimicrobial resistance gene variability in vancomycin resistant Enterococcus faecium


Whole genome sequencing is increasingly applied to healthcare-associated vancomycin resistant Enterococcus faecium (VREfm) outbreak investigations using single bacterial colonies from individual patients. However, within-patient diversity could complicate transmission resolution. We sequenced 14 colonies from VREfm positive rectal swabs over a 1-month period on a haematology unit. In total, 224 isolates from 11 patients were sequenced. Carriage of 2-3 sequence types was detected in 27% of patients. Presence of antimicrobial resistance genes and plasmids was variable within isolates from the same patient and sequence type. We identified two dominant sequence types (ST80 and ST1424), with two putative transmission clusters of two patients within ST80, and a single cluster of six patients within ST1424. We found transmission resolution was impaired using fewer than 14 colonies, and therefore there is a need to capture and consider VREfm within-patient diversity to ensure accurate resolution of transmission networks.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This work was supported by the Chief Scientist Office (Scotland) through the Scottish Healthcare Associated Infection Prevention Institute (Reference SIRN/10). The authors acknowledge the Research/Scientific Computing teams at The James Hutton Institute and NIAB for providing computational resources and technical support for the "UK's Crop Diversity Bioinformatics HPC" (BBSRC grant BB/S019669/1), use of which has contributed to the results reported within this paper. Bioinformatics and Computational Biology analyses were further supported by the University of St Andrews Bioinformatics Unit which is funded by a Wellcome Trust ISSF award [grant 105621/Z/14/Z].

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I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.


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Access to isolates and clinical data was approved by the NHS Scotland Biorepository Network (Ref TR000126) and University of St Andrews Research Ethics Committee (Ref MD12651).

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