Caffeic acid phenethyl ester synergistically enhances the antifungal activity of fluconazole against resistant Candida albicans

Background: Owing to the increased morbidity and mortality associated with invasive fungal infections, treatments with a combination of antifungal agents are often considered. Caffeic acid phenethyl ester (CAPE), a major active component of propolis, possesses many biological activities, including antibacterial, antiviral, antioxidant, anti-inflammatory, and anticancer effects. Purpose: This study aimed to evaluate the interaction between CAPE and fluconazole (FLC) against Candida albicans. Methods: Microdilution checkerboard and time-kill assays were employed to evaluate the in vitro interaction between CAPE and FLC. The data obtained from the checkerboard tests were analyzed by the fractional inhibitory concentration index (FICI). The antifungal activity of the CAPE and FLC combination was evaluated in vivo in a Caenorhabditis elegans model of infection. Results: We observed that when used in combination, CAPE acted synergistically with FLC against FLC-resistant clinical isolates of C. albicans. In addition, the CAPE-FLC combination significantly extended the longevity and reduced fungal burden in C. elegans when compared with treatment with FLC or CAPE alone. Conclusion: These results indicate that the use of CAPE and FLC in combination has considerable therapeutic potential against resistant C. albicans.