Abstract
Fifty years ago, no effective treatment of invasive fungal infections was known. In the absence of treatment, diagnosis was given little importance and often made at autopsy. Introduction of amphotericin B into clinical practice in the 1950's, followed by flucytosine changed everything. Despite its toxicity, amphotericin B deoxycholate proved to be a potent, broad spectrum antifungal. In the next decade, intravenous miconazole and oral clotrimazole were introduced but seemed to lack promise. It was only in the 1980's when ketoconazole and then itraconazole and fluconazole were introduced that the potential of oral, well tolerated broad spectrum antifungal agents was realized. In the 1990's lipid formulations of amphotericin B and voriconazole came into clinical trials and were significant additions. The first echinocandin, caspofungin, was introduced in the 1990's. Commercial success prompted development of two very similar echinocandins, micafungin and anidulafungin. Now, this cornucopia of new antifungals appears to be at an end, with the newer azoles, echinocandins and a monoclonal antibody (Mycograb) now in development appearing to offer no major advantages. Trials in which existing drugs are used in combination may expand our therapeutic arsenal a little. Perhaps the next leap forward will be in better diagnostic tests so that empirical therapy will be more and more replaced by treatment of diagnosed infection.
