Comparative Trial of Ketoconazole and Nystatin for Prevention of Fungal Infection in Neutropenic Patients Treated in a Protective Environment

Abstract

In a randomized trial we compared ketoconazole (400 mg once daily, 27 patients) and nystatin (3 × 10⁶ units four times daily, 29 patients) for prevention of fungal infection in neutropenic patients undergoing marrow transplantation in a protective environment. Fewer weekly surveillance cultures contained Candida species in ketoconazole recipients than in nystatin recipients (70 [26%] of 274 vs. 151 [47%] of 322; P < .001). When all fungi were considered, the difference in colonization was less but was still significant (117 [43%] of 274 vs. 173 [54%] of 322; P = .01), primarily due to increased colonization of the rectum with Torulopsis glabrata among ketoconazole recipients (P< .001). No difference in the incidence of local mucosal infection was seen. Two disseminated fungal infections occurred, both in nystatin recipients. Compliance with ketoconazole was significantly better than was compliance with nystatin (96% vs. 68%; P < .001), but similar effects on colonization were found in an analysis adjusting for compliance. Ketoconazole was better tolerated and more effective than nystatin in reducing colonization due to Candida species but was also associated with significantly increased rates of colonization with T. glabrata.