Evaluation of the Antifungal Effect of Fluconazole and Ivermectin against Candida albicans

Background: Ivermectin is (macrocyclic lactones) which are products or chemical derivatives of soil microorganisms belonging to the fungus Streptomyces avermitilis. Objective: The aim of the study is to evaluate the antifungal efficacy of Fluconazole and Ivermectin individually and in combination against Fluconazole-resistant Candida albicans isolates in vitro and in an in vivo rat model. Methodology: Twenty-five Fluconazole-resistant C. albicans isolates were tested for synergistic effects of Fluconazole and Ivermectin. Thirty-two male rats with/without infections will received treatments and fungal burden and survival was assessed. The antifungal efficacy was determined by measuring the zone of inhibition in a well diffusion experiment. Results: The MIC was 3.7 µg for Ivermectin and 11.1 µg for Fluconazole. Antifungal assay of Ivermectin alone (8µg) showed large inhibition zone (15.1 mm) compared to (3.7µg) showed inhibition zone (11.9 mm) and (1 µg) small inhibition zone (8.63mm). Antifungal assay of Ivermectin in combination with Fluconazole (8-11µg) show large inhibition zone (40 mm) compared to (3.7-11µg) less inhibition zone (25.9 mm) and last combination (1-11µg) show small inhibition zone (12.1mm). Animal study of Ivermectin shows the best combination with Fluconazole which showed faster healing time and reduce size of infection from (2-0.2cm) and disappeared redness of skin and return growth of hair is (8-11 µg) of Ivermectin. Conclusion: Ivermectin showed potent antifungal activity against Fluconazole-resistant C. albicans with MICs ranging from 3.7-100µg/ml. Combining Ivermectin and Fluconazole demonstrated synergistic effects leading to faster treatment response and complete resolution of fungal infection within 21 days in the in vivo model.