title: Whole-genome sequencing reveals transmission of vancomycin-resistant Enterococcus faecium in a healthcare network.
abstract: BACKGROUND
  Bacterial whole-genome sequencing (WGS) has the potential to identify reservoirs of multidrug-resistant organisms and transmission of these pathogens across healthcare networks. We used WGS to define transmission of vancomycin-resistant enterococci (VRE) within a long-term care facility (LTCF), and between this and an acute hospital in the United Kingdom (UK).
  
  
  METHODS
  A longitudinal prospective observational study of faecal VRE carriage was conducted in a LTCF in Cambridge, UK. Stool samples were collected at recruitment, and then repeatedly until the end of the study period, discharge or death. Selective culture media were used to isolate VRE, which were subsequently sequenced and analysed. We also analysed the genomes of 45 Enterococcus faecium bloodstream isolates collected at Cambridge University Hospitals NHS Foundation Trust (CUH).
  
  
  RESULTS
  Forty-five residents were recruited during a 6-month period in 2014, and 693 stools were collected at a frequency of at least 1 week apart. Fifty-one stool samples from 3/45 participants (7 %) were positive for vancomycin-resistant E. faecium. Two residents carried multiple VRE lineages, and one carried a single VRE lineage. Genome analyses based on single nucleotide polymorphisms (SNPs) in the core genome indicated that VRE carried by each of the three residents were unrelated. Participants had extensive contact with the local healthcare network. We found that VRE genomes from LTCF residents and hospital-associated bloodstream infection were interspersed throughout the phylogenetic tree, with several instances of closely related VRE strains from the two settings.
  
  
  CONCLUSIONS
  A proportion of LTCF residents are long-term carriers of VRE. Evidence for genetic relatedness between these and VRE associated with bloodstream infection in a nearby acute NHS Trust indicate a shared bacterial population.
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Box 157, Hills Road, Cambridge, CB2 0QQ, UK. hjb60@medschl.cam.ac.uk.
authors.forename: Hayley J
authors.initials: HJ
authors.lastname: Brodrick
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Box 157, Hills Road, Cambridge, CB2 0QQ, UK. ker37@medschl.cam.ac.uk.
authors.forename: Kathy E
authors.initials: KE
authors.lastname: Raven
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Box 157, Hills Road, Cambridge, CB2 0QQ, UK. eh439@cam.ac.uk.
authors.forename: Ewan M
authors.initials: EM
authors.lastname: Harrison
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Box 157, Hills Road, Cambridge, CB2 0QQ, UK. eb544@medschl.cam.ac.uk.
authors.forename: Beth
authors.initials: B
authors.lastname: Blane
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Box 157, Hills Road, Cambridge, CB2 0QQ, UK. sr731@medschl.cam.ac.uk.
authors.forename: Sandra
authors.initials: S
authors.lastname: Reuter
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Box 157, Hills Road, Cambridge, CB2 0QQ, UK. et317@cam.ac.uk.|Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, CB2 0QQ, UK. et317@cam.ac.uk.|Cambridge Public Health England Microbiology and Public Health Laboratory, Box 157, Hills Road, Cambridge, CB2 0QQ, UK. et317@cam.ac.uk.
authors.forename: M Estée
authors.initials: ME
authors.lastname: Török
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. parkhill@sanger.ac.uk.
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Box 157, Hills Road, Cambridge, CB2 0QQ, UK. sjp97@medschl.cam.ac.uk.|Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, CB2 0QQ, UK. sjp97@medschl.cam.ac.uk.|Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. sjp97@medschl.cam.ac.uk.|London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK. sjp97@medschl.cam.ac.uk.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
mesh_terms: D003428:Cross Infection / Q000382:microbiology; D016984:Enterococcus faecium / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D005243:Feces / Q000382:microbiology; D016680:Genome, Bacterial; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology*; D006801:Humans; D008134:Long-Term Care; D008137:Longitudinal Studies; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D017422:Sequence Analysis, DNA / Q000379:methods*; D065507:Vancomycin-Resistant Enterococci / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*