Capability of serum to convert streptomycin to cytotoxin in patients with aminoglycoside-induced hearing loss

Individual variations in sensitivity to the ototoxic effects of aminoglycos ide antibiotics are well documented. Our research demonstrates that there i s an apparent difference in serum from patients who are resistant or suscep tible to aminoglycoside ototoxicity. In the first study, the cytotoxicity o f sera from patients with and without hearing loss after various time perio ds following the discontinuation of aminoglycoside treatment was assayed us ing the isolated outer hair cell toxicity assay. The results indicate that sera from patients with hearing loss were significantly more toxic than ser a from patients with normal hearing or minimal hearing loss. This toxicity may persist for up to 1 year after discontinuation of aminoglycoside therap y. In a second study, sera were obtained from patients who had received ami noglycoside therapy several years previously. None of these sera was toxic to isolated outer hair cells in vitro. Streptomycin was then incubated with the sera or a protein fraction isolated from sera, and the incubation mixt ures were tested for toxicity. The percentage of damaged outer hair cells w as significantly higher when streptomycin had been treated with sera or a s erum protein fraction from patients with hearing loss (58 +/- 10% and 68 +/ - 9%, respectively) than with sera or a serum protein fraction from a contr ol group (10 +/- 5% and 17 +/- 4%, respectively). In addition, several incu bation mixtures were analyzed using high performance liquid chromatography. A new chromatographic peak was only found in the incubations of streptomyc in with serum protein from patients with hearing loss. The results suggest that sera from individuals sensitive to aminoglycoside antibiotics may meta bolize these drugs to cytotoxins. (C) 1999 Elsevier Science B.V. All rights reserved.