The Comparative Ototoxicities of Gentamicin, Tobramycin and Dibekacin in the Guinea Pig A Functional and Morphological Cochlear and Vestibular Study

Abstract

The cochleo- and vestibulotoxicities of a new aminoglyco-sidic antibiotic, dibekacin, have been compared, in the guinea pig, with those of gentamicin and tobramycin. Besides an untreated control group, three groups of pigmented guinea pigs have been treated with 20 consecutive daily subcutaneous injections of one of these antibiotics respectively, with a dosage of 90 mg/kg/day (30 times the recommended human therapeutic dose which is the same for the three aminosides studied: 3 mg/kg/day). The auditory and vestibular functions in the awake animal were studied respectively by the measurement of thresholds of click-evoked responses at the auditory cortex and by the recording of eye movements (electronystagmography) during damped sinusoidal rotatory stimulation. These functions were monitored before, during and after the treatments in a few guinea pigs in each group, chronically implanted with auditory cortex and periocular electrodes. These functions were assessed only at the end of the experiments in the other guinea pigs, just before sacrifice, 2-3 months after conclusion of the treatments. The inner ear receptors were then evaluated morphologically. The evaluations were based on remaining hair cell counts using surface preparations for the cochlea or serial sections for the crista ampullaris, maculae utriculi and sacculi of one ear for each guinea pig. Scanning electron microscopic examinations of the other ear was also performed. These functional and morphological observations, which correlate quite precisely, indicate that gentamicin has been severely toxic, both cochlearly and vestibularly, that tobramycin has been cochleotoxic-like gentamicin-and also, though to a lesser degree, vestibulotoxic, while dibekacin appeared to be vestibulotoxic-like tobramycin but far less cochleotoxic.