Comparison of the effect of non-antifungal and antifungal agents on Candida isolates from the gastrointestinal tract.

Abstract

Non-antifungal drugs appear promising in treatment of opportunistic infections of Candida spp. that are often resistant to current antifungals. The broth macrodilution method (NCCLS M27-P document) was used to compare the antifungal activity of trifluoperazine, propranolol, and lansoprazole with that of ketoconazole and amphotericin B, using 50 yeast isolates from the GI tract. The minimum fungicidal concentrations (MFCs), resistance rates and the time required for fungicidal activity of the drugs (2 - 48 hours) were determined. The most effective antifungal activity was exhibited by trifluoperazine. Its MFC was 32 µg/mL for Candida albicans (3.3% resistance) and Candida spp. (0% resistance) yeasts, and 64 µg/mL for Candida tropicalis with 10% resistance. The MFC for C. albicans and Candida spp. was comparable to that of ketoconazole. However, the time required for the inhibitory effect (6 hr) was shorter than that of ketoconazole (48 hr) or amphotericin B (24 hr). The time required for the inhibitory activity on C. tropicalis was 24 hr, which was shorter than that of ketoconazole and amphotericin B (48 hr). A considerable number (40%) of Candida spp. showed resistance to ketoconazole, and 20% of C. tropicalis showed resistance to amphotericin B. Trifluoperazine, an antipsychotic drug, exhibited effective antifungal activity with the MFC, comparable to ketoconazole (32 µg/mL). Among the three yeast groups, C. tropicalis showed resistance to trifluoperazine and amphotericin B, and Candida spp. was considerably resistant to ketoconazole. Trifluoperazine could be considered as an alternative antifungal when encountering Candida spp. resistant to current antifungals.