In Vitro Activity of Isavuconazole against Rare Yeast - Rhodotorula, Geotrichum, Saccharomyces, and Pichia Species

George R. Thompson III, Nathan P. Wiederhold, Deanna A. Sutton, Annette Fothergill, Thomas F. Patterson

Abstract: 

Background: The emergence of less common, but clinically important, fungal pathogens including the rare yeast has contributed to the substantial morbidity and mortality observed in immunocompromised patients. These organisms can be resistant or refractory to existing antifungal agents. We sought to evaluate the activity of the new triazole Isavuconazole against these difficult pathogens.
Methods: Minimum inhibitory concentrations (MICs) were measured for Isavuconazole, voriconazole, posaconazole, fluconazole, amphotericin B, and flucytosine against 7 Geotrichum capitatum (formerly Blastoschizomyces capitatum), 18 Saccharomyces cervesiae, 11 Pichia, and 14 Rhodotorula species in accordance with the M27-A2 reference method. Minimum fungicidal concentrations were also measured for each agent.
Results: Isavuconazole demonstrated excellent in vitro activity against each species tested. MIC90 values ranged between and 0.03 to 0.5 mg/L against all tested isolates. The geometric mean MICs of Isavuconazole were similar to that of voriconazole and similar or less than those of posaconazole, fluconazole, amphotericin B, and flucytosine for all species tested. Activity was also maintained against nine Rhodotorula isolates that were resistant to fluconazole. The MFC50 and MFC90 values for the extended spectrum triazoles including Isavuconazole were lower than those of fluconazole, amphotericin B, and flucytosine. However MFC90 values often exceeded the highest concentration tested and exhibited wide variability.
Conclusions: Isavuconazole is a welcome addition to the growing antifungal armamentarium with potent in vitro activity against emerging yeast pathogens. Although this agent may be useful in the treatment of the rare yeast, clinical data are needed to verify these results.

2009
    • Focus on Fungal Infection 19 (2009)