title: In vitro activities of voriconazole, itraconazole, and amphotericin B against Blastomyces dermatitidis, Coccidioides immitis, and Histoplasma capsulatum.
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 microg/ml. Itraconazole had MIC(90)s of 0.06 microg/ml for H. capsulatum, 0.125 microg/ml for B. dermatitidis, and 1 microg/ml for C. immitis. The MIC(90)s of voriconazole were 0.25 microg/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 microg/ml, respectively. It was less active against C. immitis, with MFCs ranging from 0.5 to >16 microg/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 microg/ml, respectively. Both azoles were fungicidal for some isolates of H. capsulatum, with MFC(50)s of 2 and 8 microg/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.
authors.affiliation: Mycotic Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
authors.forename: R K
authors.initials: RK
authors.lastname: Li
authors.forename: M A
authors.initials: MA
authors.lastname: Ciblak
authors.forename: N
authors.initials: N
authors.lastname: Nordoff
authors.forename: L
authors.initials: L
authors.lastname: Pasarell
authors.forename: D W
authors.initials: DW
authors.lastname: Warnock
authors.forename: M R
authors.initials: MR
authors.lastname: McGinnis
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001758:Blastomyces / Q000187:drug effects*; D003045:Coccidioides / Q000187:drug effects*; D006658:Histoplasma / Q000187:drug effects*; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D017964:Itraconazole; D000666:Amphotericin B; D065819:Voriconazole