The ototoxicity of repetitive chronic aminoglycoside administration. An experimental study

To determine whether previous exposure to an aminoglycoside antibiotic would predispose an individual to more severe ototoxic reactions upon subsequent administration, guinea pigs were given up to three courses of gentamicin at a dose of 50 or 100 mg/kg. Each course was separated by a period of 4 weeks, and animals were killed 4 weeks after the date of last injection. Cochlear pathology was assessed by the surface preparation technique and phase contrast microscopy. Detailed counts of sensory hair cell populations were recorded and statistically analysed. No significant ototoxic hair cell loss occurred following the repetition of 50 mg/kg. At 100 mg/kg, repetitive administration produced a significant and cumulative destruction of the most basal outer and inner hair cells. Using this protocol, it was concluded that if the initial exposure proved ototoxic, further administration of gentamicin increased subsequent sensory hair cell loss.