In Vitro Activities of Voriconazole, Itraconazole, and Amphotericin B against Blastomyces dermatitidis , Coccidioides immitis , and Histoplasma capsulatum

Abstract

ABSTRACT The in vitro activity of voriconazole was compared to those of itraconazole and amphotericin B against the mold forms of 304 isolates of three dimorphic fungi, Blastomyces dermatitidis , Coccidioides immitis , and Histoplasma capsulatum . MICs were determined by a broth microdilution adaptation of the National Committee for Clinical Laboratory Standards M27-A procedure. RPMI 1640 medium was used for tests with voriconazole and itraconazole, whereas Antibiotic Medium 3 with 2% glucose was used for amphotericin B. Minimum fungicidal concentrations (MFCs) were also determined. Amphotericin B was active against all three dimorphic fungi, with MICs at which 90% of the isolates tested are inhibited (MIC 90 s) of 0.5 to 1 μg/ml. Itraconazole had MIC 90 s of 0.06 μg/ml for H. capsulatum , 0.125 μg/ml for B. dermatitidis , and 1 μg/ml for C. immitis . The MIC 90 s of voriconazole were 0.25 μg/ml for all three fungi. Amphotericin B was fungicidal for B. dermatitidis and H. capsulatum with MFCs at which 90% of strains tested are killed (MFC 90 s) of 0.5 and 2 μg/ml, respectively. It was less active against C. immitis , with MFCs ranging from 0.5 to >16 μg/ml. Voriconazole and itraconazole were lethal for most isolates of B. dermatitidis , with MFC 50 s and MFC 90 s of 0.125 and 4 μg/ml, respectively. Both azoles were fungicidal for some isolates of H. capsulatum , with MFC 50 s of 2 and 8 μg/ml for itraconazole and voriconazole, respectively; neither had a lethal effect upon C. immitis . Our results suggest that voriconazole possesses promising activity against these important human pathogens.