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Cefotiam was evaluated by a comparative open-label randomized trial with cephalothin in the therapy of skin and soft tissue infections in 39 patients. The most common organism isolated was Staphylococcus aureus (78%). We established evidence of primary infection with gram-negative bacilli in four patients, three of whom were diabetic. Eight patients had mixed infections or superinfections. No patient was evaluated as a treatment failure; for 10 of 39 patients we were unable to recover an etiological agent but demonstrated a clinical cure. Cefotiam was found to be as effective as cephalothin in the therapy of skin and soft tissue infections.