Clinical challenges and unmet needs in the management of complicated skin and skin structure, and soft tissue infections.

BACKGROUND: Skin and soft tissue infections remain among the most frequently encountered infections in surgery, and their severity ranges from mild cellulitis to severe, necrotizing infections with high incidences of morbidity and mortality. Most commonly, these disorders result from skin lesions in a susceptible host, but sometimes develop following hematogenous spread from a previously unknown focus.

METHODS: The current literature was reviewed to provide an up-to-date summary of the microbiology, diagnosis, pathogenesis, and therapy of complicated skin and soft tissue infections. Special conditions are also described, such as cellulitis, bite wounds and diabetic foot infections. The potential roles of several new drugs that have become available recently, or are currently in phase III clinical trials, are discussed.

RESULTS: The causative pathogens are mostly gram-positive cocci from a patient's endogenous skin flora, but complicated infections often involve gram-negative and anaerobic bacteria related to the site and source of infection. Classifications are numerous and often confusing, occasionally leading to a prolonged diagnostic workup. Therapy should be initiated immediately following clinical diagnosis, including empiric antimicrobial chemotherapy and surgical debridement, if necessary. Hospitalization is mandatory for those patients with constitutional symptoms of sepsis, failed outpatient therapy, or deeper infections, such as necrotizing fasciitis. The number and variety of resistant organisms in the community continues to increase steadily, with methicillin-resistant Staphylococcus aureus (MRSA) currently the most common. Several new drugs that are active against MRSA are becoming available, and include those active broadly against gram-positive cocci, such as quinupristin-dalfopristin, linezolid, and daptomycin. Tigecycline, a new antibiotic of the glycylcycline class, has extended broad-spectrum activity against both gram-positive and gram-negative organisms, including anaerobes and multi-resistant organisms.

CONCLUSIONS: New, promising agents, with activity against multi-drug resistant gram-positive and gram-negative organisms, are aimed at filling the gap in the treatment of complicated skin and skin-structure infections.