Systemic fungal infections: diagnosis and treatment. I. Coccidioidomycosis.

Coccidioidomycosis is a highly variable disease. Initial respiratory tract infection can lead to self-limited pneumonia, pulmonary complications, and extrapulmonary disease. The early infection requires no therapy, except in immunosuppressed patients and other selected patients. Treatment for pulmonary complications may include surgery for cavities or pyopneumothorax (resulting from rupture of a cavity) and antifungal therapy for chronic pneumonia. The majority of extrapulmonary disease occurs in the skin, bones and joints, or meninges and is an indication for treatment with antifungal agents and sometimes adjunctive surgery. Meningitis is a particularly serious consequence of dissemination and currently is best treated with intrathecal instillation of antifungal agents. Antifungal agents useful in the treatment of coccidioidomycosis are amphotericin B, which is administered intravenously and is relatively toxic, and ketoconazole, which is administered orally and whose toxicities are less serious and reversible. Because studies to compare the efficacy of these two drugs have not been performed, selecting between them for use in individual patients is most rationally based on the pharmacologic differences, which lend themselves to different clinical settings. In future years, new antifungal agents will likely be available, some of which will offer significant advantages over present therapies. Itraconazole is an imidazole related to ketoconazole, which appears to be effective and possibly less toxic than ketoconazole. Fluconazole, another imidazole, has broad antifungal activity, a long serum half-life, and excellent penetration into the cerebrospinal fluid. Thus, the pharmacology of this agent would appear ideal for use in treating coccidioidal meningitis. In addition, other compounds with different modes of action are now under investigation in preclinical studies. It is therefore likely that continued improvements will occur in the coming years in the treatment of this disease.