Interaction of carvacroland voriconazole against drug – resistant Candida strains isolated from patients with candidiasis

Abstract Objective Terpenoid phenols, especially 5-isopropyl-2-methylphenol (carvacrol), are components of plant essential oils that exhibit potent antifungal activity against a wide range of pathogens, including Ca ndida species. The purpose of this study was to determine the interaction activity of carvacrol in combination with voriconazole against Candida albicans ( C .  albicans ), C .  glabrata and C .  krusei isolates. Materials and methods The minimum inhibitory and fungicidal concentrations (MICs and MFCs) of carvacrol and voriconazole were determined against various Candida species isolated from patients with candidiasis using the Clinical Laboratory Standards Institute (CLSI) M27-A2 broth microdilution method. The nature of the interaction was studied from fractional inhibitory concentration indices (FICIs) for carvacrol plus voriconazole combination calculated from checkerboard microdilution assay. Results Carvacrol presented an antifungal effect, with mean MICs of 66.87 μg/mL for C .  albicans , 75 μg/mL for C .  glabrata and 95 μg/mL for C .  krusei isolates. The mean MICs of voriconazole against C .  albicans , C .  glabrata and C .  krusei isolates were 0.087, 1.25 and 0.35 μg/mL, respectively. Carvacrol in combination with voriconazole exhibited the synergistic anti- Candida effects against all species of Candida tested. FICI values for carvacrol plus voriconazole combination ranged from 0.370 to 0.853 for C .  albicans isolates, 0.412 to 0.625 for C .  glabrata isolates, and 0.474 to 0.748 for C .  krusei isolates. No antagonistic activity was seen in the strains tested. Conclusion From these results we suggest that carvacrol has great potential as antifungal, and that voriconazole can be supplemented with carvacrol to inhibit clinical Candida isolates.