Chemotherapy for the systemic mycoses: the prelude to ketoconazole

Successful chemotherapy of the systemic mycoses now covers a span of more than 75 years and dates to the first reported use of potassium iodide for treatment of sporotrichosis. The second drug with efficacy was stilbamidine, and its currently available successor, hydroxystilbamidine isethionate, still has a role in therapy of some patients with nonprogressive blastomycosis of the skin. The introduction in 1957 of amphotericin B marked the first time there was an effective agent for such diseases as cryptococcosis, histoplasmosis, candidosis, and with lesser success, for coccidioidomycosis, mucormycosis, and aspergillosis. However, amphotericin B is nephrotoxic, depresses bone marrow (especially erythropoeisis), and, if patients are not monitored and controlled closely, the drug produces hypokalemic muscle weakness and cardiotoxicity. Flucytosine has a narrower spectrum of activity (cryptococcosis, candidosis, cladosporiosis, and chromomycosis) but a preferable route of administration (oral). Newer agents presently available are miconazole and clotrimazole; the latter is for topical use only.