Isobolographic in vitro interactions of fluconazole with citrus essential oils against Cladosporium cladosporioides

Introduction. Cladosporium is one of the most abundant genera of environmental fungi worldwide and a very common respiratory allergen. To-date, many C. cladosporoides infections have been identified. Risk factors for C. cladosporioides infection are primarily injuries, metabolic disorders, organ transplantation and autoimmune diseases, among others. Objective. The aim of the study was to assess the type of pharmacodynamic interactions between fluconazole and some selected essential oils: orange, mandarin, lemon and grapefruit, in an in vitro study against C. cladosporioides. Materials and method. Experiments were carried out using the plate cultivation method. Fluconazole was tested against C. cladosporioides at concentrations ranging from 0.05–3.3 mg / ml, and the activity of essential oils added to PDA medium at concentrations ranging from 1–30%. The dose-effect curves for the collected results were determined with by the log- probit method. Isobolographic analysis of the results allowed determining the type of interactions between fluconazole and the tested essential oils. Results. Lemon essential oil was the most active, and in a concentration of 1% it inhibited the growth of C. cladosporioides by 21%. Isobolographic analysis showed that the combination of fluconazole with orange and grapefruit essential oil had an additive interaction, and with mandarin and lemon – an additive interaction with a tendency to synergy in the plate culture test for C. cladosporioides. Conclusions. The use of isobolographic analysis can contribute to the introduction of natural substances with the desired activities into the pharmacotherapy of many infections and diseases. The use of natural substances can also help to reduce the number of side-effects caused by conventional and standard therapies.