Ototoxicity of topical azithromycin solutions in the guinea pig

Objective: To investigate possible ototoxic effects of topical azithromycin (AZ) in the guinea pig. Design: A prospective, controlled animal study. Setting: The University of Texas Southwestern Medical Center at Dallas. Participants: Twenty-three pigmented guinea pigs were given single, unilateral middle ear applications of a solution containing 3%(n=3),2%(n=5),1%(n=5), or 0.5% (n=5) AZ or saline (n=5). The contralateral ear served as the untreated control. Main Outcome Measures: The animals were observed for behavioral changes for 2 weeks and then humanely killed. The ears were processed for anatomical evaluation. Morphologic changes were analyzed by quantitation of middle ear changes and cochlear inner and outer hair cell loss. Statistical analysis was performed to examine effects by dose. Results: Analysis revealed extensive middle and inner ear changes associated with all formulations of AZ. Moderate correlation was found between the extent of middle ear changes and AZ concentration (r²=0.59), whereas a strong correlation was seen between inner ear damage and AZ concentration (r²=0.94). Both inner and outer hair cells were affected, with inner hair cell damage consistently greater than outer hair cell damage. Conclusions: The results of this study demonstrate that ototopical AZ can cause middle ear changes and significant hair cell loss in the guinea pig. This finding, together with previous clinical reports, indicates that topical AZ should be used with caution in the clinical setting.