COMMUNITY-ONSET METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS CAUSING COMPLICATED SKIN AND MUSCULOSKELETAL INFECTIONS IN BRAZIL: CLINICAL AND MOLECULAR ASPECTS ASSOCIATED WITH SEVERITY

Aim This study aimed to assess clinical, phenotypic and genomic characteristics of community-onset methicillin-resistant Staphylococcus aureus (CO-MRSA) causing complicated skin, soft tissue and musculoskeletal infections (cSSTMI) in a large city in Brazil. Independent predisposing factors for disease severity was evaluated. Method Patients with community-onset cSSTI and musculoskeletal infections evaluated from June 2022 to January 2024 had tissue samples collected through biopsy, punch, or aspiration. All MRSA isolates underwent genetic sequencing. Patients were prospectively followed during one month after hospital discharge. Multivariate analysis was performed to determine independent factors associated with worst outcomes. Results A total of 118 patients with cSSTI were included, male were 60.2%, with median age of 41.1 years (SD+-26,1). Any type of immunosuppression condition was identified in 45.8%. Skin and soft tissue infections accounted for 59.2% of cases, while osteomyelitis and septic arthritis were 12.7% and 7.6%, respectively. Pain was the predominant symptom (86.4%), and fever occurred in only 42.4% of cases. Sepse was diagnosed in 22%. Surgical procedures were performed in 21.1% of cases. Relapse and death occurred in 13.5% and 7.6%, respectively. Among the 145 isolated microorganisms, 25.5% were multidrug-resistant (MDR), 61.4% were Staphylococcus aureus (S. aureus), while 24.1% were MRSA. Genomic analysis revealed that 35 MRSA isolates belonged to clonal complexes (CC) 5, 8, and 30, identified SCCmec types were IV (a,c) and II, all exhibiting a high load of virulence genes and mobile genetic elements associated with antibiotic resistance. The predominant clone was ST105-MRSA-II-t2 (20%). Infections caused by S. aureus showed worse outcomes due to the need of surgical procedure (p=0.035), length of hospital stay (p=0.01), and severity (p=0.016), and no statistically significant differences were found in clinical outcomes when comparing methicilin susceptible S.aureus and MRSA. The presence of fever, leukocitosis and lesion depth were significantly associated with case severity (p<0.001), while genomic traits of MRSA showed no predictive correlation with outcomes. Conclusions This is the first study in Latin America to assess the role of CO-MRSA causing cSSTMI with clinical outcomes. We identified worryingly higher rates of CO-MRSA, impacting on the empirical therapy for cSSTMI. Importantly, ST105-MRSA-II-t2 was the predominant clone, previously undescribed in CO-SSTIs and musculoskeletal infections, and associated with MDR, highlighting the need for rigorous global surveillance of clonal spread in South America. Fever, leukocytosis, and deep infection were associated with severity and should prompt empirical coverage for MRSA.