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Antimicrobial Agents and Chemotherapy, April 2003, p. 1376-1381, Vol. 47, No. 4
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.4.1376-1381.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

In Vitro Antifungal Activity of Micafungin (FK463) against Dimorphic Fungi: Comparison of Yeast-Like and Mycelial Forms

Toru Nakai,1,2* Jun Uno,1 Fumiaki Ikeda,2 Shuichi Tawara,2 Kazuko Nishimura,1 and Makoto Miyaji1

Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, Chuo-ku, Chiba 260-8673,1 Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Yodogawa-ku, Osaka 532-8514, Japan2

Received 22 October 2002/ Returned for modification 23 December 2002/ Accepted 15 January 2003

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 µg/ml), while it was very weakly active against their yeast-like forms (MIC range, 32 to >64 µg/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.

* Corresponding author. Mailing address: Department of Infectious Diseases, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 2-1-6, Kashima, Yodogawa-ku, Osaka 532-8514, Japan. Phone: 81-6-6390-1146. Fax: 81-6-6304-5367. E-mail: toru_nakai{at}po.fujisawa.co.jp.

Antimicrobial Agents and Chemotherapy, April 2003, p. 1376-1381, Vol. 47, No. 4
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.4.1376-1381.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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