The relative importance of human and animal sources of vancomycin-resistant Enterococcus faecium in immunocompromised patients in hospital. (360G-Wellcome-103387_B_13_Z)

Enterococcus faecium (Efm), a human and animal gut commensal, has emerged as a leading nosocomial infection in immunocompromised patients. The rise of Efm has been driven by the global spread of a hospital-adapted lineage, characterised by mobile genetic elements coding for antimicrobial resistance and virulence determinants. Two further lineages are recognised, one associated with community carriage and the other livestock-associated. Vancomycin-resistant Efm (VREfm) has spread across all three lineages, and represents a significant healthcare problem responsible for outbreaks and infections in vulnerable hospitalised patients. Whole-genome sequencing (WGS) promises to close the gaps in our understanding of Efm epidemiology. I will conduct a study to investigate the hypothesis that WGS will determine the origin of VREfm in a cohort of hospitalised patients at Addenbrooke's Hospital, a centre which ranks top in VREfm bacteraemia numbers nationally. The project will consist of: i) a lo ngitudinal survey of Efm gut carriage in patients with haematological malignancy and first hospital admission and their ward contacts; ii) cross-sectional surveys of Efm in farm slurry and wastewater in the East of England; iii) WGS and bioinformatic analysis of recovered isolates to determine the origin, within-host evolution, transmission of VREfm between patients, and a possible zoonotic source.