Some new approaches to the evaluation of antifungal activities of amphotericin B.
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概要
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<I>In vitro</I> and <I>in vivo</I> antifungal activities of amphotericin B (AMPH [B]) were compared with those of ketoconazole, fluconazole, itraconazole, miconazole, nystatin and flucytosine, which have been used for systemic fungal infection or are undergoing of clinical trials in Japan. From the viewpoint of MIC values, AMPH [B] was found to show the lowest among the tested antifungals, without any sign of emergence of resistant strains and was considered still to be a useful antifungal agent.<BR>The sensitivity disk agar (SDA), which has been used in the determination of MIC in bacteria in Japan, was found to be suitable medium for the determination of antifungal activities, when compared with Sabouraud dextrose (SGA) agar and yeast morphology agar (YMA). Actually, the MIC values of SDA were about one-fourth, those of YMA and SGA.<BR>Effectiveness of orally administered AMPH [B] against <I>Candida albicans</I> infection in mice was also studied and the results showed that 50 to 500mg/kg of AMPH [B] can protect mice from infection. However, it was also found that <I>C. albicans</I> was still recovered from the kindney of surviving mice 30 days after the treatment with AMPH [B]. HPLC analysis proved that the serum level of AMPH [B] after oral administration can reach to the vicinity of the MIC values of 0.01 to 0.5μg/ml. The importance of sub-MIC of AMPH [B] was also suggested in the elimination of the fungus from the infected animals. Results on the combination effect of oral AMPH [B] with antifungal BRM, lentinan, were also repoorted.
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