Prevention of aminoglycoside-induced hearing loss.

This review discusses the current problem of ototoxicity associated with the worldwide use of aminoglycoside antibiotics. Pathology and pathophysiology of cochlear and vestibular damage have long been recognized as a preferential destruction of hair cells beginning in the cochlea with the outer hair cells of the lower turns. This is accompanied by high frequency hearing loss progressing to lower frequencies during and even after treatment with these drugs. A novel hypothesis of the underlying biochemical mechanism is based on the formation of free radicals by an aminoglycoside-iron complex. A protective treatment against aminoglycoside-induced hearing loss by co-administration of iron chelators has been successfully documented in guinea pig. This pharmacological intervention does not change serum levels of aminoglycosides nor their antibacterial efficacy. Since iron chelators are established therapeutic drugs, the proposed treatment should lend itself to clinical application. Aminoglycosides, long established for their high efficacy and low cost, may thus continue to play an important role in combating infectious diseases.