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Ketoconazole treatment of coccidioidal meningitis
J R Graybill1, D A Stevens, J N Galgiani
1Audie L. Murphy Memorial Veterans' Hospital, San Antonio, Texas 78284.
Abstract:
Fifteen patients with coccidioidal meningitis were treated with high doses of ketoconazole for up to 4 years. Five patients were treated with ketoconazole alone. One clinically failed, one developed hepatotoxicity, and three achieved remission of meningitis. One patient received intrathecal AMB in addition to ketoconazole for only 2 weeks before continuing on ketoconazole alone. He improved, but discontinued ketoconazole because of nausea and vomiting, and suffered a lethal relapse. Nine patients received ketoconazole in combination with prolonged courses of intrathecal AMB. Two patients were failures from nausea and vomiting, and the remaining seven either improved or experienced remission. The clinical responses appeared to be similar in patients receiving high-dose ketoconazole, either alone or combined with AMB, suggesting that there is no clinically significant antagonism of the drugs. Nausea and vomiting are significant limitations of high-dose ketoconazole. Ketoconazole alone is effective in some patients with coccidioidomycotic meningitis.
Insights
High-dose ketoconazole showed effectiveness in treating coccidioidal meningitis, with or without amphotericin B. Nausea and vomiting were significant side effects limiting treatment duration.
Area of Science:
- Mycology
- Infectious Diseases
- Clinical Pharmacology
Background:
- Coccidioidal meningitis is a severe fungal infection requiring effective treatment.
- High-dose ketoconazole has been explored as a therapeutic option.
Purpose of the Study:
- To evaluate the efficacy and tolerability of high-dose ketoconazole in patients with coccidioidal meningitis.
- To assess the potential interaction between ketoconazole and intrathecal amphotericin B.
Main Methods:
- Retrospective analysis of 15 patients with coccidioidal meningitis treated with high-dose ketoconazole.
- Treatment regimens included ketoconazole alone or in combination with intrathecal amphotericin B.
- Clinical outcomes and adverse events were recorded.
Main Results:
- Three of five patients treated with ketoconazole alone achieved remission.
- Seven of nine patients treated with ketoconazole and intrathecal amphotericin B improved or achieved remission.
- Nausea and vomiting were common dose-limiting toxicities for ketoconazole.
Conclusions:
- High-dose ketoconazole can be effective for coccidioidal meningitis, either as monotherapy or combination therapy.
- No significant drug antagonism was observed between ketoconazole and intrathecal amphotericin B.
- Adverse effects, particularly gastrointestinal intolerance, necessitate careful patient monitoring.