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Synergistic interaction of carvacrol and fluconazole on growth inhibition of Candida albicans in vitro and in vivo mouse model

Fereshteh Beheshtirooy, Fahimeh Alizadeh, Esmaeel Panahi Kokhdan & Alireza Khodavandi

Sydowia 72: 207-214

Published online on July 6th, 2020

Candida albicans is a major human fungal pathogen. Infections caused by the C. albicans are a challenge to antifungal treatment, especially in immunocompromised patients. Antifungal combinations that target critical cellular pathways are a mainstay of candidiasis care. To improve current approaches for treatment of gastrointestinal candidiasis and gain insights into the underlying synergistic interaction, we studied the effect of carvacrol alone and in combination with fluconazole by analysing in vitro and in vivo susceptibility of C. albicans. Susceptibility of oral clinical isolates of C. albicans were assessed using the CLSI reference method. BALB/c mouse were given as the sole food source food containing C. albicans. The mice were treated intragastrically with carvacrol and fluconazole alone and in combination. The quantification of the antifungal agent treatments was submitted for microbiological and histopathological examination. Combination of carvacrol with fluconazole demonstrated partial synergistic (66.67 %) and indifferent (33.33 %) effects with FIC values 0.56-1.50. Gastrointestinal candidiasis was confirmed by colony counts of homogenized liver, as well as by histological examination. Carvacrol in combination with fluconazole was more efficacious than carvacrol and fluconazole alone at reducing the fungal loads (P < 0.01). Taken together, our study shows that carvacrol and fluconazole combination effects can be effectively queried in C. albicans cells, which could provide a means to test novel therapeutic strategies.

Keywords: Candidiasis, Fluconazole, Gastrointestinal tract.

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