In vitro susceptibility of dermatomycoses agents to six antifungal drugs and evaluation by fractional inhibitory concentration index of combined effects of amorolfine and itraconazole in dermatophytes

Authors

  • Takashi Tamura,

    1. Department of Clinical Laboratory Science, Graduate School of Medical Technology
    2. Eiken Chemical, Taito-ku, Tokyo, Japan
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  • Miwa Asahara,

    1. Department of Clinical Laboratory Science, Graduate School of Medical Technology
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  • Mikachi Yamamoto,

    1. Laboratory of Space and Environmental Medicine, Graduate School of Medicine
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  • Mariko Yamaura,

    1. Laboratory of Space and Environmental Medicine, Graduate School of Medicine
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  • Mitsuru Matsumura,

    1. Department of Clinical Laboratory Science, Graduate School of Medical Technology
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  • Kazuo Goto,

    1. Department of Clinical Laboratory Science, Graduate School of Medical Technology
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  • Ali Rezaei-Matehkolaei,

    1. Department of Medical Mycology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Golestan Avenue, Ahvaz
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  • Hossein Mirhendi,

    1. Department of Medical Parasitology and Mycology, School of Public Health and National Institute of Health Research, Tehran University of Medical Sciences, Tehran, Iran
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  • Miho Makimura,

    1. Teikyo University Institute of Medical Mycology
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  • Koichi Makimura

    Corresponding author
    1. Department of Clinical Laboratory Science, Graduate School of Medical Technology
    2. Laboratory of Space and Environmental Medicine, Graduate School of Medicine
    3. Teikyo University Institute of Medical Mycology
    4. Department of Biomedicine, General Medical Education Center
    5. Asia International Institute of Infectious Disease Control, Teikyo University, Itabashi, Tokyo
    • Correspondence

      Koich Makimura, Laboratory of Space and Environmental Medicine, Graduate School of Medicine, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan. Tel: +81 3 3964 2140; fax: +81 3 3964 8415; email: makimura@med.teikyo-u.ac.jp

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ABSTRACT

To investigate the antifungal drug susceptibility of fungi responsible for dermatomycoses, minimum inhibition concentration (MIC) tests were performed in 44 strains of dermatophytes, including Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton verrucosum, Trichophyton tonsurans, Microsporum canis, Microsporum gypseum and Epidermophyton floccosum, with six antifungal drugs (amorolfine, terbinafine, butenafine, ketoconazole, itraconazole and bifonazole) by broth microdilution assay according to Clinical Laboratory Standard Institute protocols. Six possible dermatomycosis-causing non-dermatophytic fungi were also tested. The two major causes of tinea, T. rubrum and T. mentagrophytes, showed significantly different sensitivities to ketoconazole and bifonazole. Clinically derived dermatophytes were sensitive to the six antifungal drugs tested. However, non-dermatophytes, especially Fusarium spp., tended to be resistant to these antifungal drugs. In Trichophyton spp., the MICs of non-azole drugs had narrower distributions than those of azoles. To evaluate the effects of antifungal drug combinations, the fractional inhibitory concentration index was calculated for the combination of amorolfine and itraconazole as representative external and internal drugs for dermatophytes. It was found that this combination had synergistic or additive effects on most dermatophytes, and had no antagonistic effects. The variation in susceptibility of clinically derived fungal isolates indicates that identification of causative fungi is indispensable for appropriately choosing effective antifungal drugs in the early stages of infection. The results of combination assay suggest that multiple drugs with different antifungal mechanisms against growth of dermatophytes should be used to treat refractory dermatomycoses, especially onychomycosis.

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