This multicenter trial compared treatment with either cefsulodin or reference antibiotics (gentamicin, tobramycin, amikacin, or ticarcillin) in 67 patients with Pseudomonas aeruginosa infection and burn injury. Safety of treatment was evaluated for all 67 patients; clinical efficacy, for 29; and bacteriologic efficacy, for 26. The average daily dose and duration of treatment for the 37 cefsulodin-treated patients were 5.6 g and 10.3 days, respectively. The percentage of total body surface burned was greater than or equal to 50% for 40% and greater than or equal to 25% for 85% of the patients. Rates of bacteriologic cure for 30 sites of infection were 64% (7/11) for skin and skin-structure infections treated with cefsulodin or reference antibiotics; 100% (1/1) for respiratory tract infections treated with cefsulodin and 33% (2/6) for those treated with reference antibiotics; and 100% (1/1) for septicemia treated with a reference antibiotic. Overall bacteriologic and clinical efficacy for cefsulodin treatment was 67% (8/12) and 73% (11/15), respectively, and for treatment with a reference antibiotic was 56% (10/18) and 64% (9/14), respectively. Cefsulodin was found to be safe and comparable in efficacy to reference antibiotics in this patient population.