Synergistic Interactions between Linalool and Some Antimycotic Agents against Candida spp. as a Basis for Developing New Antifungal Preparations

The incidence of superficial infections, including oral candidiasis, has recently increased significantly. Their treatment is quite difficult due to the growing resistance of Candida spp. to antifungal agents. Therefore, it is necessary to search for novel antimycotics or alternative antifungal therapies. The purpose of the study was to evaluate the antifungal activity of natural terpene—linalool (LIN)—against both reference fungi belonging to yeasts and Candida spp. isolates from the oral cavities of immunocompromised, hemato-oncology patients. Moreover, its mechanism of action and interactions with selected antifungal drugs or antiseptics were investigated. The broth microdilution technique, ergosterol or sorbitol tests, and a checkerboard method were used for individual studies. The LIN showed potential activity toward studied strains of fungi with a minimal inhibitory concentration (MIC) in the range of 0.5–8 mg/mL and fungicidal effect. This compound was also found to bind to ergosterol in the yeast cell membrane. Additionally, the interactions between LIN with antiseptics such as chlorhexidine, cetylpyridinium, and triclosan showed beneficial synergistic effect (with FIC = 0.3125–0.375), or an additive effect with silver nitrate and chlorquinaldol (FIC = 0.625–1). Moreover, statistically significant differences in MIC values were found for the synergistic combinations of LIN. No interaction was indicated for nystatin. These results confirm that the LIN seems to be a promising plant component used alone or in combination with other antimycotics in the prevention and treatment of superficial fungal infections. However, further clinical trials are required.