Fluconazole in the Treatment of Persistent Coccidioidomycosis
Treatment of chronic coccidioidomycosis can be difficult. There are only a few effective drugs. The best established drug, amphotericin B, must be administered parenterally and is highly toxic. Miconazole was the first imidazole to be tested against Coccidioides immitis. The use of miconazole is limited by the fact that it must be administered parenterally, the carrier solvent is toxic, and since the drug is cleared rapidly, it must be administered several times each day. Ketoconazole was the first orally absorbed azole shown to have activity against С immitis. Ketoconazole is often effective in extrameningeal infection; however, its usefulness is limited by a high rate of recurrence after treatment is discontinued.Attempts to reduce rates of relapse by using higher doses have been frustrated by the occurrence of toxic effects.
Chemical manipulation of the azole structure has provided several new antifungal agents. Itraconazole is currently undergoing evaluation and appears to have promise. Fluconazole is a triazole that is the first of these agents not highly bound to protein. This probably accounts for its large volume of distribution and its excellent penetration into the cerebrospinal fluid. Fluconazole has good activity in murine coccidioidomycosis but has not been previously tested in humans. For these reasons, we undertook a clinical evaluation of the toxicity and efficacy of fluconazole in patients with persistent coccidioidomycosis.
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