During the past several years substantial progress has been made in the development of new antifungal agents active against systemic fungal infections. Neverthless, despite the adverse effects associated with amphotericin B, it remains the golden standard therapy for most serious mycoses.
Five antifungal agents are commercially available in Japan for the treatment of systemic infections caused by fungi. These are amphotericin B, flucytosine, miconazole, fluconazole and itraconazole.
Flucytosine is a water-soluble analogue of cytosine that has a narrow spectrum of activity, which includes most strains of
Cryptococcus neoformans and
Candida sp. Most other fungi are resistant or have variable susceptibility. Flucytosine is usually administered in combination with amphotericin B to treat systemic mycoses, and in rare instances may be used alone. When flucytosine is used as a single agent, resistance often develops during therapy, especially in cryptococcal infections.
Miconazole was the first of the azoles used in the treatment of fungal infections in Japan, and reports of its efficacy in treating cryptococcosis or candidiasis have varied. Because of the development of other less toxic azoles, the utility of miconazole has diminished considerably.
Fluconazole was the first of the new triazoles and was approved for use in 1989. It has several therapeutic benefits and pharmacologic properties that differ from those of ketoconazole, and in addition, it is much less toxic than ketoconazole. It is highly water-soluble and can be administered intravenously to patients who are too ill to take medication orally.
Itraconazole is an orally active triazole derivative with broad-spectrum antifungal activity. A major difference from fluconazole is its greater activity against aspergillosis.
New antifungal agents are now under intense study. With their development and use in combination chemotherapy, we can expect further improvements in the treatment of opportunistic fungal infections.
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