Comparative actions of four aminoglycoside antibiotics on the vestibular function in guinea-pigs

This study was designed to assess the actions of 4 representative aminoglycoside antibiotics on the vestibular functions in guinea-pigs as evidenced by the measurements of the vestibulo-ocular reflex (VOR) either in the horizontal (HVOR) or in the vertical plane (VVOR). VOR responses were evaluated over a wide range of stimulation frequencies prior to and after 10 and 18 days of a multiple dose regimen with dibekacin (150 mg/kg), gentamicin (100 mg/kg), netilmicin (150 mg/kg), tobramycin (100 mg/kg) or saline. All drugs or saline were given intramuscularly twice a day. The labirinthine function was found to be differently impaired by drug administration. Gentamicin induced severe vestibular impairment, which had early onset. Dibekacin greatly reduced all VOR responses, but changes occurred after a longer period of time. Tobramycin and netilmicin induced slight vestibular impairment only after 18 days of treatment. Tobramycin affected both HVOR and VVOR responses at the high frequencies, while netilmicin impaired only the HVOR. Histological examination of vestibular epithelia was conducted by using the Scanning Electron Microscope (SEM). Gentamicin and dibekacin greatly damaged both the cristae of semicircular canals and utriculi, structures which are involved in the generation of VOR responses. Conversely, tobramycin provoked damages only in the cristae of semicircular canals and netilmicin did not affect the vestibular sensory epithelia. These findings indicate that each aminoglycoside produces characteristic actions on the vestibular function which depend on the damage distribution in the labirinthine structures. Among the aminoglycoside examined, netilmicin appears to possess the lowest potential for producing impairment of the vestibular function.