Affiliation:
1. 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
2. Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-06092
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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
166 articles.
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