Laboratory evaluation of new antifungal agents against rare and refractory mycoses

Abstract

An increase in refractory invasive fungal infections in the setting of marrow/solid organ transplantation and other immune-compromising clinical entities has provided the impetus for the development of new, more efficacious/less toxic antifungal agents. This review (1) examines currently available laboratory methods for the in-vitro evaluation of these new agents against both yeasts and filamentous fungi; (2) provides a summary of the most attractive investigational agents currently undergoing clinical trials/development; and (3) outlines the major refractory mycoses in contemporary medicine. Fluconazole-resistant Candida spp., Trichosporon spp., zygomycetous genera, the endemic mycoses, Scedosporium, Aspergillus, and Fusarium spp., and an ever-expanding list of lesser-known hyaline and phaeoid genera inciting invasive fungal infections comprise the bulk of refractory mycoses in the immune-compromised host. In-vitro data generated from reference-based antifungal susceptibility testing methods indicate an increased armamentarium of potentially efficacious agents against most of these mycoses. The newly approved antifungal agents caspofungin and voriconazole, used either as monotherapy or in combination regimens, have a significantly improved spectrum of activity over previously available therapeutic options. Correlation of clinical outcomes with investigational agents demonstrating in-vivo/in-vitro activity will provide critical information needed for the development of clinically significant minimum inhibitory concentration interpretative breakpoints.