In vivo Anti-fungal Activity of the Essential Oil Fraction from Thymus Species and in vitro Synergism with Clotrimazole

The antifungal activity of the essential oil fraction from Thymus magus, and its major component thymol, against Candida albicans was investigated in vitro and in vivo. The combined effects of the oils and clotrimazole, a commonly used antifungal drug for treatment of external candidiasis, were evaluated in this study. In experimental vaginal candidiasis the essential oil fraction of T. magnus resulted in relatively milder inhibition of fungal growth following the inoculation of test mice compared to clotrimazole. However, new fungal growth was not detected up to 12 days after cessation of treatment. In contrast, in a similar experiment using clotrimazole, C. albicans was detected in the $12^{th}$ day post-treatment with the sample. This result indicates that T. magnus oil could be a promising drug to control vaginal candidiasis. In checkerboard titer tests, the combination of clotrimazole with the essential oil fraction of T. magus or T. quinquecostatus resulted in significant synergism, with FIC indices between 0.14 and 0.27 against C. albicans, while clotrimazole combined with thymol, the major component of these oils, produced only an additive effect, with FIC indices ranging between 0.50 and 1.00. Thus, the prominent synergistic effects of clotrimazole combined with T. magus essential oil indicate that these compounds may be an effective treatment for C. albicans infections.