Evaluation of the safety of 1% voriconazole ear drops for the treatment of tympanic membrane perforation-associated suppurative otomycosis.

Abstract

Otomycosis is a common otolaryngologic condition commonly complicated by tympanic membrane perforation (TMP). Although topical voriconazole has been found effective in TMP-free otomycosis, data on its safety in TMP-associated otomycosis are limited. This study was conducted to determine the safety profile of 1% ear drops of voriconazole in a rabbit model of TMP-associated suppurative otomycosis due to a clinical isolate of Aspergillus terreus. The local preparation was applied three times daily for seven consecutive days. Therapeutic efficacy was assessed by otoendoscopy, while safety was established by brainstem auditory evoked potential (BAEP) assessment and scanning electron microscopy (SEM) of cochlear hair cells. Serum levels of voriconazole were also quantified to assess systemic absorption. No difference was noted in pre- and post-treatment auditory thresholds (27 ± 6.75 dB vs. 27 ± 4.83 dB, P > 0.99). SEM examination demonstrated no damage to cochlear hair cells, and serum voriconazole concentrations remained undetectable after application. The results conclude that 1% voriconazole ear drops are safe for the treatment of TMP-associated suppurative otomycosis in this animal model. Limitations are that only one species of fungi and a preparation made at home were utilized, and further studies with other pathogens and commercial preparations are needed.