Hinokitiol plus fluconazole: potent inhibitory efficacy on Candida species resistant to azole

Candida species represent the most prevalent types of yeasts affecting humans and animals. The increase in antifungal resistance has raised the issue of using these medications in tandem to improve treatment outcomes. Guided by the CLSI M۲۷-A۳ guideline, this investigation quantified the synergistic potential of hinokitiol and fluconazole against Candida albicans, C. tropicalis, C. glabrata, and C. krusei. The primary metrics for this assessment were the minimum inhibitory and fungicidal concentrations (MICs and MFCs), which were established using a broth microdilution methodology. Using data from a checkerboard microdilution test, we calculated the fractional inhibitory concentration indices (FICIs) to evaluate the interaction between hinokitiol and fluconazole. A strong synergistic interaction between hinokitiol and fluconazole was evident in every tested isolate (۱۰۰%) of fluconazole-resistant C. albicans and C. glabrata. The corresponding FICI values, falling within ranges of ۰.۳۰۴–۰.۴۹۸ and ۰.۲۹۰–۰.۴۹۲, respectively, confirm this robust synergistic activity. This activity was noted against a background of universal fluconazole resistance, with hinokitiol alone showing MIC values from ۰.۸۱ µg/ml (C. glabrata) to ۶.۹ µg/ml (C. krusei). FICI scores spanning ۰.۵۰۰ to ۰.۷۵۰ for every C. krusei strain (۱۰۰%) confirm a strictly additive pharmacological interaction between hinokitiol and fluconazole. Additionally, the FICI values for the combination of hinokitiol and fluconazole for C. tropicalis strains varied from ۰.۲۴۵ to ۰.۷۳۰, demonstrating a synergistic effect in ۱۳ (۸۶.۷%) strains and an additive effect in ۲ (۱۳.۳%) strains. This study suggests that hinokitiol may help reduce fluconazole dosages and inhibit the development of fluconazole-resistant Candida species

کلیدواژه ها:

Candida ، Fluconazole ، Hinokitiol ، Synergy