title: Whole-genome sequencing for analysis of an outbreak of meticillin-resistant Staphylococcus aureus: a descriptive study.
abstract: BACKGROUND
  The emergence of meticillin-resistant Staphylococcus aureus (MRSA) that can persist in the community and replace existing hospital-adapted lineages of MRSA means that it is necessary to understand transmission dynamics in terms of hospitals and the community as one entity. We assessed the use of whole-genome sequencing to enhance detection of MRSA transmission between these settings.
  
  
  METHODS
  We studied a putative MRSA outbreak on a special care baby unit (SCBU) at a National Health Service Foundation Trust in Cambridge, UK. We used whole-genome sequencing to validate and expand findings from an infection-control team who assessed the outbreak through conventional analysis of epidemiological data and antibiogram profiles. We sequenced isolates from all colonised patients in the SCBU, and sequenced MRSA isolates from patients in the hospital or community with the same antibiotic susceptibility profile as the outbreak strain.
  
  
  RESULTS
  The hospital infection-control team identified 12 infants colonised with MRSA in a 6 month period in 2011, who were suspected of being linked, but a persistent outbreak could not be confirmed with conventional methods. With whole-genome sequencing, we identified 26 related cases of MRSA carriage, and showed transmission occurred within the SCBU, between mothers on a postnatal ward, and in the community. The outbreak MRSA type was a new sequence type (ST) 2371, which is closely related to ST22, but contains genes encoding Panton-Valentine leucocidin. Whole-genome sequencing data were used to propose and confirm that MRSA carriage by a staff member had allowed the outbreak to persist during periods without known infection on the SCBU and after a deep clean.
  
  
  CONCLUSIONS
  Whole-genome sequencing holds great promise for rapid, accurate, and comprehensive identification of bacterial transmission pathways in hospital and community settings, with concomitant reductions in infections, morbidity, and costs.
  
  
  BACKGROUND
  UK Clinical Research Collaboration Translational Infection Research Initiative, Wellcome Trust, Health Protection Agency, and the National Institute for Health Research Cambridge Biomedical Research Centre.
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge, UK.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Harris
authors.forename: Edward J P
authors.initials: EJ
authors.lastname: Cartwright
authors.forename: M Estée
authors.initials: ME
authors.lastname: Török
authors.forename: Matthew T G
authors.initials: MT
authors.lastname: Holden
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Brown
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Ogilvy-Stuart
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ellington
authors.forename: Michael A
authors.initials: MA
authors.lastname: Quail
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
mesh_terms: D001427:Bacterial Toxins / Q000235:genetics; D002353:Carrier State / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission; D004196:Disease Outbreaks; D005098:Exotoxins / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal; D007956:Leukocidins / Q000235:genetics; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics* / Q000302:isolation & purification*; D017354:Point Mutation; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission
chemical_list: D001427:Bacterial Toxins; D005098:Exotoxins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin