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Comparative Study
. 2003 Apr;47(4):1376-81.
doi: 10.1128/AAC.47.4.1376-1381.2003.

In vitro antifungal activity of Micafungin (FK463) against dimorphic fungi: comparison of yeast-like and mycelial forms

Affiliations
Comparative Study

In vitro antifungal activity of Micafungin (FK463) against dimorphic fungi: comparison of yeast-like and mycelial forms

Toru Nakai et al. Antimicrob Agents Chemother. 2003 Apr.

Abstract

The characteristics of in vitro micafungin (FK463) antifungal activity against six species of dimorphic fungi were investigated in accordance with the NCCLS M27-A microdilution methods. MICs of micafungin, amphotericin B, itraconazole, and fluconazole for Histoplasma capsulatum var. capsulatum, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Penicillium marneffei, and Sporothrix schenckii were determined both for the yeast-like form and mycelial form. Coccidioides immitis was tested only in its mycelial form. We have clearly demonstrated that the in vitro activity of micafungin depends considerably on the growth form of dimorphic fungi. Micafungin exhibited potent activity against the mycelial forms of H. capsulatum, B. dermatitidis, and C. immitis (MIC range, 0.0078 to 0.0625 micro g/ml), while it was very weakly active against their yeast-like forms (MIC range, 32 to >64 micro g/ml). Micafungin was also more active against the mycelial forms than the yeast-like forms of Paracoccidioides brasiliensis, Penicillium marneffei, and S. schenckii. The MICs of amphotericin B were 2 to 5 dilutions lower for the mycelial forms than for the yeast-like forms of B. dermatitidis and Paracoccidioides brasiliensis. There was no apparent difference in the activity of itraconazole between the two forms. The MICs of fluconazole for the yeast-like forms were generally lower than those for the mycelial forms, and considerably so for B. dermatitidis. These results suggest that the growth form employed in antifungal susceptibility testing of dimorphic fungi can considerably influence the interpretation of results. At present, it cannot be judged whether micafungin has clinical usefulness for dimorphic fungus infections, since for most fungi it remains uncertain which growth form correlates better with therapeutic outcome. However, the results of this study warrant further investigations of micafungin as a therapeutic agent for infections caused by dimorphic fungi.

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Figures

FIG. 1.
FIG. 1.
M (A) and Y (B) growth of B. dermatitidis in the antifungal susceptibility testing.
FIG. 2.
FIG. 2.
Visual observation of MIC plates for the Y and M forms of B. dermatitidis. Test concentrations ranged from 64 (column 1) to 0.0039 μg/ml (column 15). Rows: A, MCFG at 64 to 0.0039 μg/ml; B, AMB at 8 to 0.0039 μg/ml; C, ITC at 8 to 0.0039 μg/ml; D, FLC at 64 to 0.0313 μg/ml; E, growth control (left 3 wells) and medium control (right 3 wells). MCFG showed strong inhibition to B. dermatitidis M growth (A1 to A11), whereas the Y growth was inhibited only slightly.
FIG. 3.
FIG. 3.
Microscopic observations of antifungal activity of MCFG against the M form of H. capsulatum. (A) Growth control; (B) MCFG at the MIC; (C) MCFG at 4 times the MIC; (D) MCFG at 32 times the MIC. MCFG strongly inhibited the growth of mycelia at or above the MIC, but it was not fungicidal. Bars, 100 μm.

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