Additivity interactions between fluconazole and citrus essential oils to Aspergillus fumigatus

Introduction. Aspergillus fumigatus is the most common pathogen causing allergic bronchopulmonary mycosis. The pathogenic capacity of Aspergillus fumigatus is related to its thermal tolerance and the small size of the spores which enables transfer to the respiratory tract. In the case of fungal diseases, their treatment is based on fungicidal antibiotics, such as fluconazole. Due to the growing problem of drug resistance, new therapeutic solutions are sought, especially of natural origin. Essential oils, due to their anti-bacterial, anti-fungal, anti-inflammatory and immunostimulatory properties, constitute interesting research material in the fight against mould. Objective. The aim of the study was to assess the type of pharmacodynamic interactions between fluconazole and selected essential oils: lemon, orange, tangerine, and grapefruit in an in vitro study against Aspergillus fumigatus. Isobolographic analysis of the results allowed determining the type of interactions between fluconazole and the tested essential oils. Results. According to the research results, a IC50 dose of fluconazole versus Aspergillus fumigatus IC50 = 1.87±0.88mg/ml. The most active essential oil was lemon oil, which at the concentration of 4% in medium completely inhibited the growth of Aspergillus fumigatus. Tangerine essential oil is the least active against A. fumigatus. Isobolographic analysis of the interactions between fluconazole and essential oils showed additive interactions for the combination of fluconazole with lemon, orange and grapefruit ols, and an additive interaction with a tendency to synergism for the combination of fluconazole with tangerine oil. Conclusions. Isobographic analysis can contribute to the introduction of natural substances into the therapy of many diseases.