Laboratory evaluation of new antifungal agents against rare and refractory mycoses

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.