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 out-break 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 andmovement 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). Unrec-ognizedMRSA 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. IMPORTANCE Using whole-genome sequencing, we showed that a large and prolonged outbreak of methicillin-resistant Staphy-lococcus aureus was due to the clonal spread of a specific strain with genetic elements adapted to the hospital environment. Un