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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
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.
Key words antifungal combination, fractional inhibitory concentration index, Trichophyton mentagrophytes, Trichophyton rubrum.
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