Antifungal activity of nonantifungal drugs

The antifungal activity of synthetic, nonchemotherapeutic compounds, antineoplastic agents and antibacterial drugs, such as sulphonamides, has been known since the early 20(th) century (1932). In this context, the term 'nonantifungal' is taken to include a variety of compounds that are employed in the management of pathological conditions of nonfungal infectious etiology but have been shown to exhibit broad-spectrum antifungal activity. In this review, the antifungal properties of compounds such as chlorpromazine, proton pump inhibitors, antiarrhythmic agents, cholesterol-lowering agents, antineoplastic and immunosuppressive agents, antiparasitic drugs and antibiotics are described. Since fungi are eukaryotic cells, they share many pathways with human cells, thus increasing the probability of antifungal activity of 'nonfungal drugs'. The potential of these drugs for treatment of fungal infections has been investigated sporadically using the drugs alone or in combination with 'classic' antifungal agents. A review of the literature, supplemented with a number of more recent investigations, suggests that some of these compounds enhance the activity of conventional antifungal agents, eliminate natural resistance to specific antifungal drugs (reversal of resistance) or exhibit strong activity against certain fungal strains in vitro and in animal models. The role of these agents in the epidemiology and in the clinical manifestations of fungal infections and the potential of certain drugs for treatment of invasive fungal infections require further investigation.