Hospital-Associated MRSA Genotypes Causing Complicated Community-Onset Skin and Musculoskeletal Infections

Stefânia Bazanelli Prebianchi^1*Ingrid Nayara Santos¹Isabelle Frois Brasil Tannus¹Rafael Brull Tuma¹Mariana Kurihara¹Mauro Jose Salles^2*

• ¹Federal University of São Paulo, São Paulo, Brazil
• ²Department of Medicine, Federal University of São Paulo, São Paulo, Brazil

Objectives: To assess clinical and epidemiological characteristics, and phenotypic and genomic risk factors associated with severity and death in complicated community-onset skin, soft tissue, and musculoskeletal infections (cSSTMIs) caused by methicillin-resistant Staphylococcus aureus (MRSA). Methods: Patients with cSSTMIs were investigated between June 2022 to January 2024 and followed for one month after hospital discharge. Tissue samples were obtained through biopsy, punch, or fluid aspiration. All MRSA isolates underwent genomic sequencing. Factors associated with poor outcomes were analyzed using multivariate regression analysis, complemented by penalized regression (LASSO) with stratified cross-validation and sensitivity analyses to mitigate the risk of overestimation given the limited MRSA sample size. Results: A total of 118 patients were studied, 60.2% male, with a mean age of 41.1 years (±SD 26.1). Recurrence and death occurred in 13.5% and 7.6% of cases, respectively. Diagnostic yielded 145 microorganisms, 61.4% were S. aureus, 24.1% being MRSA and 25.5% multidrug-resistant. Thirty-five MRSA strains belonged to clonal complexes 5, 8, and 30, with a predominance of the ST105-MRSA-II-t2 clone. Deep tissue involvement was associated with an increased likelihood of severe outcomes, with an odds ratio of 13.2 (p = 0.036), whereas penalized regression confirmed deep infection as the most stable predictor. MRSA genomic characteristics were not independently correlated with outcomes. Conclusions: High rates of antimicrobial resistance were observed in cSSTMIs, suggesting the need for empirical coverage, particularly in deep infections that were significantly associated with adverse outcomes.