Abstract
Due to the limited range of antifungals available to treat genital Candida infections and the emergence of resistant isolates, attention has focused on the antifungal potency of natural compounds with promising biological properties. To examine whether eugenol synergises the in vitro efficacy of voriconazole against Candida strains isolated from the genital tract of mares. In vitro experiment. The antifungal activity of eugenol and voriconazole was evaluated using the broth microdilution assay (CLSI- M27-A3). Synergism of eugenol and voriconazole against genital Candida isolates was evaluated by the microdilution checkerboard method. Minimum inhibitory concentration (MIC) values for eugenol and voriconazole ranged from 400 to 800µg/mL and 1 to 8µg/mL, respectively, for C.tropicalis isolates, and from 200 to 400µg/mL for eugenol and 2 to 16µg/mL for voriconazole against C.krusei isolates. Eugenol decreased the arithmetic mean MIC for voriconazole against C.tropicalis and C.krusei isolates from 2.66 to 0.46µg/mL and 7.77 to 0.41µg/mL respectively. The fractional inhibitory concentration index (FICI) values for the eugenol-voriconazole combination ranged from 0.25 to 0.88 and 0.19 to 0.63 for C.tropicalis and C.krusei isolates respectively. A synergistic effect of eugenol in combination with voriconazole was observed for 83.3% of C.tropicalis and 77.7% of C.krusei isolates. Antagonistic activity was not seen in any of the isolates tested. Since in vitro antifungal susceptibility tests are not systematic analyses, any selection bias could influence the results. In addition, in vitro susceptibility does not uniformly predict clinical success in vivo. Eugenol showed fungistatic and fungicidal effects against genital Candida isolates and, in combination, synergised the antifungal effects of voriconazole. The eugenol-voriconazole combination can lay the foundation for a therapeutic approach against isolates in which azole resistance has increased over time.
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