A little over 15 years ago, the antifungal drugs which could be used for systemic mycoses were amphotericin B, flucytosine and miconazole. For superficial mycoses, there was oral griseofulvin for dermatophytes and a series of topical agents ranging from Whitfield's ointment to the newer imidazoles such as clotrimazole and miconazole. Over the intervening years, this picture has changed dramatically to the extent that for systemic mycoses there is now a range of antifungals leading to a choice of therapy depending, to some extent, on the disease and the underlying condition of the patient. For superficial fungal infections there is a similar choice of therapy with the additional benefit that, whereas formerly the treatment of superficial mycoses had been a lengthy process, there is now the possibility of high rates of remission with substantially reduced durations of treatment. These advances in antifungal therapy have been accomplished by three main strategies-the reformulation of old compounds, the synthesis of new molecules and the use of immunotherapy. The polyene antifungal group is a large family of drugs which are derived from Streptomycete species but only three, amphotericin B, nystatin and natamy-cin, are currently used in the treatment of human disease. The activity of the polyene antifungals depends on inhibition of the formation of the fungal cell membrane, which in turn leads, amongst other effects, to an increase in cell permeability which is reversible at low concentrations. Coincident binding to mammalian cell membranes is believed to form the basis for polyene toxicity in man, which has limited the intravenous dose of amphotericin B to a maximum of 1 mg/kg per day and the parenteral use of the other polyenes entirely. This counteracts a potential advantage of this group of drugs, their broad spectrum of activity against the major systemic pathogenic fungi.
展开▼
