Flucytosine Treatment and Resistance Mechanisms

Abstract

Flucytosine is a synthetic antimycotic compound which, after being taken up by susceptible fungal cells, is converted to 5-fluorouracil and subsequent intermediate metabolites that are responsible for inhibition of fungal DNA, RNA, and protein synthesis. Due to primary resistance of yeast, flucytosine is used mainly in combination. Flucytosine administered in combination with amphotericin B remains the standard of care for cryptococcal meningitis, and the drug continues to have a role in the treatment of Candida infections which are life threatening or in circumstances where drug penetration may be problematic. It is also used in combination to treat severe systemic mycoses, such as cryptococcosis, chromoblastomycosis, and aspergillosis. Recently, 5-FC has been combined with gene therapy approaches and used as a chemotherapeutic drug to inhibit tumor growth and in curing lesions. In this chapter we review the mechanism of action of flucytosine, its resistance mechanisms, as well as the utility of combining it with other antifungal agents. The available new data may lead to improved dosing practices and a ``rebirth'' of this agent as a useful adjunct in the treatment of serious fungal infections.