Difficult-to-Treat Skin and Soft Tissue Infections Caused by Panton-Valentine Leukocidin-Producing Community-Associated Methicillin-Resistant Staphylococcus aureus: A Case Series

<b>Background</b>: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a genetically distinct lineage from healthcare-associated MRSA (HA-MRSA), often producing Panton-Valentine leukocidin (PVL) and causing severe skin and soft tissue infections (SSTIs) in otherwise healthy individuals. <b>Methods</b>: We describe five cases of PVL-positive CA-MRSA SSTIs admitted to the Infectious Diseases Unit of the University Hospital "Paolo Giaccone," Palermo, Italy, between 2024 and 2025. Case inclusion followed the CDC criteria for CA-MRSA. Microbiological identification was performed using MALDI-TOF mass spectrometry, and antimicrobial susceptibility testing followed EUCAST standards. PVL gene presence was confirmed by polymerase chain reaction. <b>Results</b>: Clinical management included surgical drainage, systemic antibiotic therapy, and decolonization of both patients and close contacts. Long-acting lipoglycopeptides (oritavancin or dalbavancin) were evaluated as therapeutic options to achieve clinical resolution. <b>Conclusions</b>: PVL-positive CA-MRSA infections are characterized by recurrence, intrafamilial clustering, and frequent therapeutic failure with standard oral agents. Effective management requires an integrated approach combining prompt surgical drainage; systemic therapy, preferably including long-acting lipoglycopeptides; and comprehensive decolonization of all close contacts.