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Antimicrobial Agents and Chemotherapy, June 2000, p. 1734-1736, Vol. 44, No. 6
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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

Ren-Kai Li,1 Meral A. Ciblak,1 Nicole Nordoff,2 Lester Pasarell,2 David W. Warnock,1,* and Michael R. McGinnis2

Mycotic Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333,1 and Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-06092

Received 23 September 1999/Returned for modification 7 March 2000/Accepted 21 March 2000

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 (MIC90s) of 0.5 to 1 µg/ml. Itraconazole had MIC90s of 0.06 µg/ml for H. capsulatum, 0.125 µg/ml for B. dermatitidis, and 1 µg/ml for C. immitis. The MIC90s 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 (MFC90s) 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 MFC50s and MFC90s of 0.125 and 4 µg/ml, respectively. Both azoles were fungicidal for some isolates of H. capsulatum, with MFC50s 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.


* Corresponding author. Mailing address: Mycotic Diseases Branch, Centers for Disease Control and Prevention, 1600 Clifton Rd., N.E., Mailstop C-09, Atlanta, GA 30333. Phone: (404) 639-3053. Fax: (404) 639-2780. E-mail: dsw8{at}cdc.gov.


Antimicrobial Agents and Chemotherapy, June 2000, p. 1734-1736, Vol. 44, No. 6
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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