Strain Differences in Bloodstream and Skin Infection MRSA isolated between 2019-2021 in a Single Health System

S. aureus is a common cause of skin and soft tissue infections (SSTIs) and has recently become the most common cause of bloodstream infections (BSIs), but whether the strains causing these two clinical syndromes overlap has not been studied adequately. USA300/500 (clonal complex [CC] 8-ST8) and USA100 (CC5-ST5) have dominated among methicillin-resistant S. aureus (MRSA) strains in the U.S. since the early 2000s. We compared the genomes of unselected MRSA isolates from 131 SSTIs with those from 145 BSIs at a single U.S. center in overlapping periods in 2018-2021. CC8 MRSA was more common among SSTIs and CC5 was more common among BSIs, consistent with prior literature. Based on clustering genomes with a threshold of 15 single nucleotide polymorphisms (SNPs), we identified clusters limited to SSTI patients and separate clusters exclusively comprising BSI patients. However, we additionally identified 8 outbreak clusters that included at least one SSTI and one BSI isolate. This suggests that virulent MRSA strains are transmitted from person-to-person locally in the healthcare setting and the community and that single lineages are often capable of causing both SSTIs and BSIs. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The authors were supported by the National Institute of Health (NIH) (grant number RO1 AI139188) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of University of Pennsylvania gave ethical approval for this work. Protocols Genomics of S. aureus Colonization after Initial and Recurrent Skin Infections and the Impact of Antibiotics (831208) and Retrospective MRSA Bacteremia (843095) were approved August 2018 and May 2020, respectively. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data is available on NCBI Sequence Read Archive PRJNA918392, PRJNA751847.