Treatment of histoplasmosis.

Histoplasmosis is an endemic mycosis, which is most prevalent in the Ohio and Mississippi valleys of North America. The causative organism is a dimorphic fungus, Histoplasma capsulatum. Histoplasmosis can present as a self-limited disease or cause life-threatening diseases resulting in considerable morbidity and mortality. Treatment is appropriate in patients with diffuse acute pulmonary infection, chronic pulmonary infection, mediastinal granuloma causing obstruction of important structures, or disseminated infection. Other chronic forms of disease such as fibrosing mediastinitis and broncholithiasis are unresponsive to pharmacologic treatment. Options for therapy include amphotericin B or one of its lipid formulations, and ketoconazole, itraconazole, or fluconazole. Recently, newer antifungal agents have been evaluated in animals models of histoplasmosis. Of these, a new triazole, posaconazole (SCH56592) appears most promising. Generally, amphotericin B or one of the lipid formulations is recommended as initial treatment in patients with more extensive diseases, felt to be ill enough to require hospitalization, and itraconazole for those who have milder illness, or to complete treatment after patients respond to amphotericin B. The role of intravenous formulation of itraconazole for severe histoplasmosis is unknown because studies comparing it with amphotericin B have not been conducted.