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

W. E. Dismukes, A. M. Stamm, J. R. Graybill, P. C. Craven, D. A. Stevens, R. L. Stiller, G. A. Sarosi, G. Medoff, C. R. Gregg, H. A. Gallis, B. T. Fields, R. L. Marier, T. A. Kerkering, L. G. Kaplowitz, G. Cloud, C. Bowles, S. Shadomy

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Abstract

The pharmacology, in-vitro mycologic activity, toxicity, and efficacy of ketoconazole were studied in a Phase-II evaluation by the National Institute 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.

Original languageEnglish (US)
Pages (from-to)13-20
Number of pages8
JournalAnnals of Internal Medicine
Volume98
Issue number1
StatePublished - 1983

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National Institute of Allergy and Infectious Diseases (U.S.)
Ketoconazole
Mycoses
Blastomycosis
Coccidioidomycosis
Sporotrichosis
Cryptococcosis
Histoplasmosis
Therapeutics
National Institutes of Health (U.S.)
Anorexia
Nausea
Vomiting
Pharmacology

ASJC Scopus subject areas

  • Medicine(all)

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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. / Dismukes, W. E.; Stamm, A. M.; Graybill, J. R.; Craven, P. C.; Stevens, D. A.; Stiller, R. L.; Sarosi, G. A.; Medoff, G.; Gregg, C. R.; Gallis, H. A.; Fields, B. T.; Marier, R. L.; Kerkering, T. A.; Kaplowitz, L. G.; Cloud, G.; Bowles, C.; Shadomy, S.

In: Annals of Internal Medicine, Vol. 98, No. 1, 1983, p. 13-20.

Research output: Contribution to journalArticle

Dismukes, WE, Stamm, AM, Graybill, JR, Craven, PC, Stevens, DA, Stiller, RL, Sarosi, GA, Medoff, G, Gregg, CR, Gallis, HA, Fields, BT, Marier, RL, Kerkering, TA, Kaplowitz, LG, Cloud, G, Bowles, C & Shadomy, S 1983, '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', Annals of Internal Medicine, vol. 98, no. 1, pp. 13-20.
Dismukes, W. E. ; Stamm, A. M. ; Graybill, J. R. ; Craven, P. C. ; Stevens, D. A. ; Stiller, R. L. ; Sarosi, G. A. ; Medoff, G. ; Gregg, C. R. ; Gallis, H. A. ; Fields, B. T. ; Marier, R. L. ; Kerkering, T. A. ; Kaplowitz, L. G. ; Cloud, G. ; Bowles, C. ; Shadomy, S. / 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. In: Annals of Internal Medicine. 1983 ; Vol. 98, No. 1. pp. 13-20.
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abstract = "The pharmacology, in-vitro mycologic activity, toxicity, and efficacy of ketoconazole were studied in a Phase-II evaluation by the National Institute 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.",
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T2 - Emphasis on toxicity and clinical response in 52 patients. National institute of allergy and infectious diseases collaborative antifungal study

AU - Dismukes, W. E.

AU - Stamm, A. M.

AU - Graybill, J. R.

AU - Craven, P. C.

AU - Stevens, D. A.

AU - Stiller, R. L.

AU - Sarosi, G. A.

AU - Medoff, G.

AU - Gregg, C. R.

AU - Gallis, H. A.

AU - Fields, B. T.

AU - Marier, R. L.

AU - Kerkering, T. A.

AU - Kaplowitz, L. G.

AU - Cloud, G.

AU - Bowles, C.

AU - Shadomy, S.

PY - 1983

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N2 - The pharmacology, in-vitro mycologic activity, toxicity, and efficacy of ketoconazole were studied in a Phase-II evaluation by the National Institute 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.

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