Antifungal therapeutics for dimorphic fungal pathogens.

Dimorphic fungi cause several endemic mycoses which range from subclinical respiratory infections to life-threatening systemic disease. Pathogenic-phase cells of Histoplasma, Blastomyces, Paracoccidioides and Coccidioides escape elimination by the innate immune response with control ultimately requiring activation of cell-mediated immunity. Clinical management of disease relies primarily on antifungal compounds; however, dimorphic fungal pathogens create a number of challenges for antifungal drug therapy. In addition to the drug toxicity issues known for current antifungals, barriers to efficient drug treatment of dimorphic fungal infections include natural resistance to the echinocandins, residence of fungal cells within immune cells, the requirement for systemic delivery of drugs, prolonged treatment times, potential for latent infections, and lack of optimized standardized methodology for in vitro testing of drug susceptibilities. This review will highlight recent advances, current therapeutic options, and new compounds on the horizon for treating infections by dimorphic fungal pathogens.