P022 Luliconazole—a novel potent imidazole activity against Aspergillus niger and Aspergillus flavus causing otomycosis
Authors: Sukumar Bavadharani , Premamalini Thayanidhi , Shree Sasikumar Nivetha , Kindo Anupma Jyoti 
Published: September 2022

Abstract

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

Background and Objectives
Suppurative otitis media (SOM) is characterized by the inflammation of the middle ear and mastoid, tympanic membrane perforation as well as discharge. The tympanic membrane perforation may result in increased exposure of the middle ear to pathogens. Aspergillus niger and Aspergillus flavus, are the most common causative agents of otomycosis with worldwide distribution, when it spreads from the external auditory canal to adjacent anatomical structures, it is classified as Aspergillus invasive otitis externa. Aspergillus otomycosis treatment is initiated by thorough cleaning of the ear canal, accomplished with suction, and drying with cotton swabs. In developing countries, SOM is a major cause of preventable hearing loss, its incidence ranges from 7% to 46% and is common amongst children of lower socioeconomic status. Treatment of SOM is directed at debridement and drying the ear with topical antifungal agents. Extensive surgical debridement and systemic antifungal therapy are needed in cases of refractory otomycosis or Aspergillus invasive otitis externa. Despite this management, treatment failure may result from suboptimal therapeutic management caused by antifungal agent toxicity. 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. The aim of the present study was to evaluate the efficacy of luliconazole in comparison to routinely used antifungals on clinical isolates of A. niger and A. flavus.

Methods
The study was carried out in the Department of Microbiology, SRIHER, Chennai. A total of 55 (29 A. niger and 26 A. flavus) strains of Aspergillus isolates obtained from clinical otomycosis cases were confirmed based on macroscopic and microscopic identification by Lacto Phenol Cotton Blue mount and slide culture technique. Antifungal susceptibility patterns of all the Aspergillus isolates to itraconazole, voriconazole, posaconazole, and luliconazole were determined by broth microdilution method as per Clinical Laboratory Standards Institute (CLSI) M38-A2 guidelines.

Results
The lowest minimum inhibitory concentration (MIC) geometric mean (GM) (0.00309 μg/ml) was attributed to luliconazole followed by posaconazole (0.18409 μg/ml), voriconazole (1.02727 μg/ml) and itraconazole (11.0091 μg/ml). Also, among the azoles tested, luliconazole had the lowest MIC50 and MIC90 values of 0.00098 μg/ml and 0.00781 μg/ml respectively. Among the triazoles tested posaconazole had a lower MIC50 and MIC90 values of 0.125 μg/ml and 0.25 μg/ml. Being the drug of choice for invasive aspergillosis voriconazole had a slightly higher MIC50 and MIC90 value of 1 μg/ml and 2 μg/ml. Luliconazole was found to be more effective even for pan azole-resistant isolates (n = 3) with lower MIC values.

Conclusion
The results of this study showed that luliconazole had an excellent in vitro activity against all Aspergillus isolates with a lower MIC GM, MIC50, and MIC90 values than the triazoles tested. Hence, this novel imidazole antifungal agent can be regarded as appropriate Candidate for the treatment of otomycosis caused by A. niger and A. flavus strains. Also, 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.