Antifungal activity against Scedosporium species and novel assays to assess antifungal pharmacodynamics against filamentous fungi

Abstract

The saprophytic moulds Scedosporium prolificans and Scedosporium apiospermum/Pseudallescheria boydii are an increasing cause of invasive fungal infections in immunocompromised hosts. The growing importance and high mortality rates of invasive disease caused by these fungi necessitates the search for newer treatment strategies. However, clinically available antifungal agents have modest to minimal activity against these organisms that has been confirmed by suboptimal responses in the clinic. Due to this limited in vitro activity and poor clinical response, antifungal combinations and high-dose regimens are frequently recommended to treat these refractory infections. However, development of a pharmacodynamic basis for antifungal dosing in scedosporiosis has been hampered by the limitations in the application of traditional microbiological techniques and endpoints for Scedosporium species. Newer quantitative and qualitative assays have demonstrated utility for measuring drug lethality in filamentous fungi, including Scedosporium species, and may aid in the development of new treatment strategies to improve patient outcomes