title: The Stealthy Superbug: the Role of Asymptomatic Enteric Carriage in Maintaining a Long-Term Hospital Outbreak of ST228 Methicillin-Resistant Staphylococcus aureus.
abstract: Whole-genome sequencing (WGS) of 228 isolates was used to elucidate the origin and dynamics of a long-term outbreak of methicillin-resistant Staphylococcus aureus (MRSA) sequence type 228 (ST228) SCCmec I that involved 1,600 patients in a tertiary care hospital between 2008 and 2012. Combining of the sequence data with detailed metadata on patient admission and movement confirmed that the outbreak was due to the transmission of a single clonal variant of ST228, rather than repeated introductions of this clone into the hospital. We note that this clone is significantly more frequently recovered from groin and rectal swabs than other clones (P < 0.0001) and is also significantly more transmissible between roommates (P < 0.01). Unrecognized MRSA carriers, together with movements of patients within the hospital, also seem to have played a major role. These atypical colonization and transmission dynamics can help explain how the outbreak was maintained over the long term. This "stealthy" asymptomatic colonization of the gut, combined with heightened transmissibility (potentially reflecting a role for environmental reservoirs), means the dynamics of this outbreak share some properties with enteric pathogens such as vancomycin-resistant enterococci or Clostridium difficile.
  
  
  OBJECTIVE
  Using whole-genome sequencing, we showed that a large and prolonged outbreak of methicillin-resistant Staphylococcus aureus was due to the clonal spread of a specific strain with genetic elements adapted to the hospital environment. Unrecognized MRSA carriers, the movement of patients within the hospital, and the low detection with clinical specimens were also factors that played a role in this occurrence. The atypical colonization of the gut means the dynamics of this outbreak may share some properties with enteric pathogens.
authors.affiliation: Hospital Preventive Medicine Service, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Laurence
authors.initials: L
authors.lastname: Senn
authors.affiliation: Hospital Preventive Medicine Service, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Clerc
authors.affiliation: Hospital Preventive Medicine Service, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Zanetti
authors.affiliation: Hospital Preventive Medicine Service, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Basset
authors.affiliation: Institute of Microbiology, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Guy
authors.initials: G
authors.lastname: Prod'hom
authors.affiliation: NIHR Oxford Biomedical Research, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Nicola C
authors.initials: NC
authors.lastname: Gordon
authors.affiliation: NIHR Oxford Biomedical Research, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Sheppard
authors.affiliation: NIHR Oxford Biomedical Research, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Derrick W
authors.initials: DW
authors.lastname: Crook
authors.affiliation: Department of Physics and Centre for Networks and Collective Behaviour, University of Bath, Bath, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: James
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
authors.forename: Harry A
authors.initials: HA
authors.lastname: Thorpe
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Feil
authors.affiliation: Hospital Preventive Medicine Service, University Hospital of Lausanne, Lausanne, Switzerland Dominique.Blanc@chuv.ch.
authors.forename: Dominique S
authors.initials: DS
authors.lastname: Blanc
mesh_terms: D002353:Carrier State / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission; D003428:Cross Infection / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004196:Disease Outbreaks; D018562:Disease Transmission, Infectious; D016680:Genome, Bacterial; D005838:Genotype; D006119:Groin / Q000382:microbiology; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D017720:Molecular Epidemiology; D012007:Rectum / Q000382:microbiology*; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission; D062606:Tertiary Care Centers
chemical_list: D004269:DNA, Bacterial