Treatment of Systemic Mycoses with Ketoconazole: Emphasis on Toxicity and Clinical Response in 52 Patients

doi:10.1059/0003-4819-98-1-13

Treatment of Systemic Mycoses with Ketoconazole: Emphasis on Toxicity and Clinical Response in 52 Patients

National Institute of Allergy and Infectious Diseases Collaborative Antifungal Study

Birmingham, Alabama; and Bethesda, Maryland

Abstract

The pharmacology, in-vitro mycologic activity, toxicity, and efficacy of ketoconazole were studied in a Phase-II evaluation by the National Institutes of Health and National Institute of Allergy and Infectious Disease Mycoses Study Group. This report emphasizes the toxicity and clinical response data in 52 patients with the following systemic mycoses: blastomycosis in 16 patients; nonmeningeal coccidioidomycosis in 13; histoplasmosis in 8; nonmeningeal cryptococcosis in 7; sporotrichosis in 7; and both blastomycosis and nonmeningeal coccidioidomycosis in 1. Maximum daily doses of ketoconazole were 100 mg in 1 patient; 200 mg in 23; 400 mg in 12; and 600 mg in 16. In 52% of the patients, duration of therapy ranged from less than 1 to 6 months, whereas in 35%, duration ranged from 7 to 12 months, and in 13%, from 12 to 22 months. In 35 patients (67%), evidence of toxicity was not seen. Nausea, anorexia, or vomiting occurred in 21%. Cure or marked improvement was shown in 27 patients (52%), whereas failure of the primary course was seen in 14 (27%) and relapse after ketoconazole was discontinued in 11 (21 %). Although this evaluation did not provide clear-cut clinical response data, our results indicate that ketoconazole, in the dosage regimens used, was more effective in patients with histoplasmosis and nonmeningeal cryptococcosis than in patients with blastomycosis and nonmeningeal coccidioidomycosis, and least effective in patients with sporotrichosis.

Article and Author Information

▸From the Division of Infectious Diseases, Department of Medicine, and Department of Biostatistics, University of Alabama School of Medicine in Birmingham, Birmingham, Alabama; and the National Institutes of Health, Bethesda, Maryland
↵* See Acknowledgments for investigators who supplied data for this report.
Ketoconazole was supplied by Janssen Pharmaceutica, New Brunswick, New Jersey.
Grant support: in part by contract NO1 AI 82570 with the Clinical and Epidemiological Studies Branch, Microbiology and Infectious Diseases Program, National Institute of Allergy and Infectious Diseases; by grant DRR RR32 from the Clinical Research Center, University of Alabama in Birmingham; by grant CA 13148 from the Comprehensive Cancer Center, University of Alabama in Birmingham; by grant RR00036-21 from the Clinical Research Center, Washington University School of Medicine; and by grant 2MO1RR00065 from the Clinical Research Center, Virginia Commonwealth University.
▸Requests for reprints should be addressed to William E. Dismukes, M.D.; Department of Medicine, University of Alabama in Birmingham, University Station; Birmingham AL 35294.