Amphotericin B in the treatment of coccidioidomycosis

In the 25 years since its introduction, amphotericin B has demonstrated clear value in the management of coccidioidomycosis. However, its effectiveness is less certain than in diseases due to other fungal aetiological agents, even when the loci of infection and in vitro drug susceptibilities are identical. The refractoriness of coccidioidomycosis may relate to the unique ability of each Coccidioides immitis spherule to release hundreds of endospores, thus maximally challenging host defence mechanisms. Amphotericin B is most likely to be effective where there is evidence of intact cell-mediated immunity against C. immitis (i.e. positive coccidioidin or spherulin skin test; low titre of complement fixing antibody), and structural damage to tissues. When bones and joints are involved, as is frequently the case, adjunctive surgical management is generally required. Patients with structural lung disease (i.e. cysts and/or cavities) show variable, often minimal, response to treatment. Amphotericin B has transformed coccidioidal meningitis from a routinely fatal disease to one where prolonged survival is possible. However, the drug must be given by the intrathecal route, and for periods of years, before the possibility of cure can be considered. Relapses of bone, joint and meningeal coccidioidomycosis are common and should be anticipated, especially in patients with impaired immunity.