Randomized, double-blind, controlled study of cefoperazone-sulbactam plus cotrimoxazole versus ceftazidime plus cotrimoxazole for the treatment of severe melioidosis

Abstract

We conducted a prospective randomized, double-blind, controlled study of cefoperazone-sulbactam (ratio, 1:1; cefoperazone 25 mg/kg/day) plus cotrimoxazole (trimethoprim-sulfamethoxazole [TMP-SMZ] at a ratio of 80:400; TMP, 8 mg/kg/day) versus ceftazidime (100 mg/kg/day) plus cotrimoxazole (TMP, 8 mg/kg/day) for the treatment of severe melioidosis. Of 219 patients enrolled in the study, 102 (47%) had culture-proven melioidosis. These patients were assigned randomly to 2 treatment groups, each with 50 patients (2 patients were excluded). Mortality rates were not significantly different between the 2 groups: 18% in the cefoperazone-sulbactam group versus 14% in the ceftazidime group. The crude difference in the mortality rate was 4%, but when adjusted for type of infection the difference was 0.9% (95% confidence interval, -3.6% to 5.4%; P = .696). The duration of defervescence and the bacteriological response of successfully treated patients were similar in both groups, and both treatment regimens were well tolerated. Cefoperazone-sulbactam plus cotrimoxazole might be used as an alternative to ceftazidime plus cotrimoxazole as treatment for severe melioidosis.