Luliconazole: A Novel Potent Imidazole Activity against Aspergillus niger and Aspergillus flavus Causing Otomycosis

Abstract

Background: Aspergillus niger and Aspergillus flavus are the most common causative agents of otomycosis with worldwide distribution. Extensive surgical debridement and systemic antifungal therapy are needed in cases of refractory otomycosis. Luliconazole is currently confirmed for the topical therapy of dermatophytosis. Moreover, it is found that luliconazole has in vitro activity against some molds and yeast species. Objectives: The aim of the present study was to evaluate the efficacy of luliconazole in comparison to routinely used triazole antifungals on Aspergillus isolates, obtained from otomycosis cases using microbroth dilution method. Materials and Methods: This study was carried out in the department of microbiology, from March 2020 to February 2022. A total of 55 strains of Aspergillus isolates obtained from otomycosis cases were confirmed based on macroscopic and microscopic identification. Antifungal susceptibility patterns of itraconazole, voriconazole, posaconazole and luliconazole were determined by broth microdilution method as per the Clinical Laboratory Standards Institute M38-A2 guidelines. Results: Among the azoles tested, the lowest minimum inhibitory concentration (MIC) geometric mean (0.00309 μg/ml), MIC50 (0.00098 μg/ml), and MIC90 (0.00781 μg/ml) values were attributed to luliconazole. Being the drug of choice for aspergillosis, voriconazole had a slightly higher MIC50 and MIC90 value of 1 μg/ml and 2 μg/ml, respectively. Even for the pan azole resistant isolates (n = 3), luliconazole was found to be more effective with lower MIC values. Conclusion: The results of this study showed that luliconazole had an excellent in vitro activity with a lower MIC values than the triazoles tested. Hence, this novel imidazole antifungal agent can be considered an appropriate candidate for the treatment of otomycosis caused by A. niger and A. flavus strains. Furthermore, luliconazole showed better efficacy with lower MIC values for pan azole resistant isolates, suggesting that it could be a potential antifungal for treating aspergillosis caused by pan azole resistant isolates.