In vitro activities of voriconazole, itraconazole, and amphotericin B against Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum

The in vitro activity of voriconazole was compared to those of itraconazole and amphotericin B against the mold forms of 304 isolates of three dimorph ic fungi, Blastomyces dermatitidis, Coccidioides immitis, and Histoplasma c apsulatum. 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 fu ngicidal concentrations (MFCs) were also determined. Amphotericin B was act ive against all three dimorphic fungi, with MICs at which 90% of the isolat es tested are inhibited (MIC(90)s) of 0.5 to 1 mu g/ml. Itraconazole had MI C(90)s of 0.06 mu g/ml for H. capsulatum, 0.125 mu g/ml for B. dermatitidis , and 1 mu g/ml for C. Bnmitis. The MIC(90)s of voriconazole were 0.25 mu g /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 mu g/ml, respectively. It was less active against C. immi tis, with MFCs ranging from 0.5 to >16 mu g/ml. Voriconazole and itraconazo le were lethal for most isolates of B. dermatitidis, with MFC(50)s and MFC( 90)s of 0.125 and 4 mu g/ml, respectively. Both azoles were fungicidal for some isolates of H. capsulatum, with MFC(50)s of 2 and 8 ug/ml for itracona zole and voriconazole, respectively; neither had a lethal effect upon C. im mitis. Our results suggest that voriconazole possesses promising activity a gainst these important human pathogens.