Genomic Epidemiology Suggests Community Origins of Healthcare-Associated USA300 Methicillin-Resistant Staphylococcus aureus

Background Hospital-onset (HO) methicillin-resistant Staphylococcus aureus (MRSA) infections have declined over the past decade due to infection control strategies; community-onset (CO) and healthcare-associated community-onset (HACO) MRSA, particularly USA300, has declined less. We examined the role of community strains to explain the difference. Methods We performed whole-genome sequencing (WGS) on MRSA clinical isolates from Cook County Health patients during 2011-2014. We defined infections as CO, HO, or HACO epidemiologically. We integrated genomic, community exposure, and statewide hospital discharge data to infer MRSA origin. Results Among 1020 individuals with available WGS, most were USA300 wound infections (580 CO, 143 HO, 297 HACO). USA300 HO, CO, and HACO infections were intermixed on the USA300 phylogeny, consistent with common strains circulating across community and healthcare settings. Community exposures (eg, substance abuse, incarceration, homelessness) were associated with HACO and HO infections, and genetically linked individuals from both groups had little overlap in healthcare facilities, supporting community origins. Most repeat infections-over months to years-occurred in individuals persistently carrying their own strains. These individuals were more likely to have genetic linkages, suggesting a role of persistent colonization in transmission. Conclusions Efforts to reduce presumed nosocomial USA300 spread may require understanding and controlling community sources and transmission networks, particularly for repeat infections. We used genomic epidemiology and statewide data to infer origins of methicillin-resistant Staphylococcus aureus(MRSA). Among individuals with hospital-onset and healthcare-associated community-onset MRSA, we identified community exposures associated with infection, but little evidence of shared exposure in healthcare settings.