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Complicated skin and soft tissue infections (cSSTIs) represent the severe form of infectious disease that involves deeper soft tissues. Involvement of methicillin-resistant Staphylococcus aureus (MRSA) further complicates cSSTI with increased hospitalization, health care costs, and overall mortality. Various international guidelines provide recommendations on the management of cSSTIs, with the inclusion of newer antibiotics. This literature-based review discusses the overall management of cSSTI, including appropriate use of antibiotics in clinical practice. Successful treatment of cSSTIs starts with early and precise diagnosis, including identification of causative pathogen and its load, determination of infection severity, associated complications, and risk factors. The current standard-of-care for cSSTIs involves incision, drainage, surgical debridement, broad-spectrum antibiotic therapy, and supportive care. In recent …