Ototoxicity of subcutaneously administered aztreonam in neonatal rats

Aztreonam (SQ 26,776) was given subcutaneously to three groups of neonatal rats at daily doses of 150, 600, and 2400 mg/kg from postnatal Days 10 through 16. Two similar groups given 400 mg of streptomycin kg-1 day-1 or 12 ml of 0.9% sodium chloride kg-1 day-1 on the same schedule served as a positive and negative control group, respectively. On postnatal Days 28 and 56, the neonates were evaluated for level of spontaneous activity and auditory and vestibular function. Half of the neonates in each group were necropsied on postnatal Day 29, and the other half on postnatal Day 57. The inner ears of all neonates were evaluated for histopathologic evidence of ototoxicity. No functional or histopathologic evidence of ototoxicity was found in any neonatal rat dosed with aztreonam or saline. However, neonates given streptomycin were hyperactive, had severely impaired hearing and vestibular function, and had morphologic changes in the sensory nerve endings of the semicircular canals, utriculus, sacculus, and cochlea. The histopathologic evidence of the ototoxic effects of streptomycin correlated highly with the functional data. Thus, under these conditions, aztreonam demonstrated no ototoxic effects in neonatal rats.