Comparative Ototoxicity of Four Aminoglycosidic Antibiotics during the Critical Period of Cochlear Development in the Rat

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Abstract
The comparative ototoxicity of four aminoglycosides (amikacin, dibekacin, gentamicin and tobramycin) was evaluated in the rat during the critical period of cochlear development. Newborn rats received a daily subcutaneous injection of one of the four antibiotics for 8 consecutive days, starting on day 8 after birth (amikacin: 225 mg/kg, dibekacin: 60 mg/kg, gentamicin and tobramycin: 45 mg/kg). Evaluation of ototoxicity was assessed one month after the end of the treatment using cochlear recordings (action potential and cochlear microphonic), surface preparations and scanning electron microscopy. No functional or structural evidence of ototoxicity was found in animals treated with dibekacin. Tobramycin had a weak ototoxic effect characterized by a slight increase in N1 latency and moderate damage to OHC stereocilia (fusion and formation of giant cilia). Gentamicin-treated animals demonstrated more severe evidence of ototoxicity including increased thresholds for CM, and a higher incidence of missing hair cells and damage to OHC stereocilia. The maximal cochlear damage was observed in amikacin-treated animals: both AP and CM thresholds were severely impaired, cell counts and SEM showed extensive loss of hair cells.

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