Impact of repeated intranasal gentamicin irrigation on auditory brainstem evoked potentials in rats

Gentamicin is a bactericidal aminoglycoside antibiotic that broadly targets Gram-negative microbes. Both human and animal studies have shown that administration of gentamicin is ototoxic by several routes of administration and results in sensorineural hearing loss due to damaged hair cell at the base of the cochlea. However, gentamicin is also administered intranasally to treat sinusitis in humans, but no animal studies have examined ototoxicity of gentamicin administered via this route. We hypothesized that intranasal irrigation of gentamicin will result in ototoxicity and impaired auditory function similar to systemic delivery. We investigated this hypothesis in Sprague-Dawley rats that received intranasal irrigations of gentamicin or saline from postnatal day (P) 21-31. We examined auditory function by assessing brainstem auditory evoked potentials in response to both broadband clicks and pure tone-pips (4, 8, 16, 24 and 32 kHz) on P41. We found significant changes in auditory function in gentamicin-exposed animals. Specifically, gentamicin-exposed animals had significantly higher thresholds in response to both clicks and tone-pips. In response to broadband clicks, there were no changes in latency for waves I through IV. However, we found significantly longer wave and interwave latencies for all waves in response to the 24 kHz tone-pip. Together, these findings suggest that intranasal administration of gentamicin results in impaired auditory function consistent with other routes of delivery.