Aspirin attenuates gentamicin ototoxicity: from the laboratory to the clinic

This article reviews recent advances in the protection from the adverse auditory or vestibular side effects associated with antibacterial treatment with aminoglycoside antibiotics. Compelling evidence from animal models suggests that reactive oxygen species are part of the initial mechanisms that trigger apoptotic and necrotic cell death in the inner ear. Consequently, antioxidants protect against aminoglycoside-induced hearing loss in animals and, importantly, they do so without compromising drug serum levels or antibacterial efficacy. While clinical studies have long confirmed the ototoxicity of aminoglycosides in human, a trial on protection was only recently reported (Sha, S.-H., Qiu, J.-H., Schacht, J., 2006. Aspirin attenuates gentamicin-induced hearing loss. New Engl. J. Med. 354, 1856-1857). Based on the finding that salicylate afforded protection in animals, the efficacy of aspirin (acetyl salicylate) was tested in a randomized double-blind placebo-controlled study in patients receiving gentamicin for acute infections. Fourteen of 106 patients (13%) met the criterion of hearing loss in the placebo group while only 3/89 (3%) were affected in the aspirin group (p=0.013). Aspirin did not influence gentamicin serum levels or the course of therapy. These results indicate that therapeutic protection from aminoglycoside ototoxicity may be extrapolated from animal models to the clinic. Furthermore, medications as common as aspirin can significantly attenuate the risk of gentamicin-induced hearing loss.