Affiliation:
1. Division of Infectious Diseases, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298-0049
Abstract
ABSTRACT
The NCCLS proposed standard M38-P describes standard parameters for testing the fungistatic antifungal activities (MICs) of established agents against filamentous fungi (molds); however, standard conditions are not available for testing their fungicidal activities (minimum fungicidal or lethal concentrations [MFCs]). This study evaluated the in vitro fungistatic and fungicidal activities of voriconazole, itraconazole, and amphotericin B against 260 common and emerging molds (174
Aspergillus
sp. isolates [five species], 23
Fusarium
sp. isolates [three species], 6
Paecilomyces lilacinus
isolates, 6
Rhizopus arrhizus
isolates, 23
Scedosporium
sp. isolates, 23 dematiaceous fungi, and 5
Trichoderma longibrachiatum
isolates). MICs were determined by following the NCCLS M38-P broth microdilution method. MFCs were the lowest drug dilutions that resulted in fewer than three colonies. Voriconazole showed similar or better fungicidal activity (MFC at which 90% of isolates tested are killed [MFC
90
], 1 to 2 μg/ml) than the reference agents for
Aspergillus
spp. with the exception of
Aspergillus terreus
(MFC
90
of voriconazole and amphotericin B, >8 μg/ml). The voriconazole geometric mean (G mean) MFC for
Scedosporium apiospermum
was lower (2.52 μg/ml) than those of the other two agents (5.75 to 7.5 μg/ml). In contrast, amphotericin B and itraconazole G mean MFCs for
R. arrhizus
were 2.1 to 2.2 μg/ml, but that for voriconazole was >8 μg/ml. Little or no fungicidal activity was shown for
Fusarium
spp. (2 to >8 μg/ml) and
Scedosporium prolificans
(>8 μg/ml) by the three agents, but voriconazole had some activity against
P. lilacinus
and
T. longibrachiatum
(G mean MFCs, 1.8 and 4 μg/ml, respectively). The fungicidal activity of the three agents was similar (G mean MFC, 1.83 to 2.36 μg/ml) for the dematiaceous fungi with the exception of the azole MFCs (>8 μg/ml) for some
Bipolaris spicifera
and
Dactylaria constricta
var.
gallopava
. These data extend and corroborate the available fungicidal results for the three agents. The role of the MFC as a predictor of clinical outcome needs to be established in clinical trials by following standardized testing conditions for determination of these in vitro values.
Publisher
American Society for Microbiology
Cited by
264 articles.
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