In vitro synergy of eugenol on the antifungal effects of voriconazole against Candida tropicalis and Candida krusei strains isolated from the genital tract of mares

Abstract

Background: 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. Objectives: To examine whether eugenol synergises the in vitro efficacy of voriconazole against Candida strains isolated from the genital tract of mares. Study design: In vitro experiment. Methods: 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. Results: Minimum inhibitory concentration (MIC) values for eugenol and voriconazole ranged from 400 to 800 µg/mL and 1 to 8 µg/mL, respectively, for C. tropicalis isolates, and from 200 to 400 µg/mL for eugenol and 2 to 16 µg/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 0.46 µg/mL and 7.77 to 0.41 µg/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. Main limitations: 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. Conclusions: 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.

Inhibitory Effect of Eugenol and trans‐Anethole Alone and in Combination with Antifungal Medicines on Candida albicans Clinical Isolates

“…Our research also shows that the constituent of Eugenia caryophyllata essential oil – eugenol – enhances miconazole and econazole action. The latest research of Sharifzadeh and Shokri [30] confirm the ability of eugenol to synergistic action with antimycotic agents against yeast form Candida genus. The authors showed that eugenol in combination with voriconazole possess synergistic potential against C. tropicalis and C. krusei isolates (FICI=0.19–0.88).…”

4-Allyl-2-methoxyphenol modulates the expression of genes involved in efflux pump, biofilm formation and sterol biosynthesis in azole resistant Aspergillus fumigatus

“…Eugenol, being a phytochemical, has already been reported to have antifungal activity in Candida spp. The MIC of eugenol have been reported in the range of 375–750 µg/mL against Candida dubliniensis and Candida tropicalis and 200–400 µg/mL against Candida krusei ( De Paula et al., 2014 ; Sharifzadeh and Shokri, 2021 ). Eugenol containing essential oils were found to transform the hyphal ultrasound and virulence factors of A. fumigatus and Trichophyton rubrum ( Gayoso et al., 2005 ).…”

Eugenol: A novel therapeutic agent for the inhibition of Candida species infection

“…Another study reported a synergistic effect of eugenol in combination with voriconazole against voriconazole-resistant C. tropicalis and C. krusei isolated from the genital tract of mares ( Sharifzadeh and Shokri, 2021 ). To this end, Dąbrowska et al (2021) reported that eugenol indicated additive and synergistic activities with econazole and miconazole against clinical isolates of C. albicans , respectively.…”