Developmental ototoxicity.

The aminoglycoside antibiotics are active bactericidal agents used for the treatment of tuberculosis and gram-negative bacterial infections. Well over 2 million patients per year receive aminoglycosides; however, a major limitation to their use is ototoxicity (cochleotoxicity and vestibulotoxicity), nephrotoxicity, and neuromuscular blockade. Ototoxicity can result from aminoglycoside administration to any patient population, including adults, fetuses, and preterm and full-term neonates. Preterm infants and experimental animals are hypersensitive to aminoglycoside ototoxicity during the period of anatomic and functional maturation of the inner ear. Developing animals, including humans, are also hypersensitive to loop diuretics and especially to the combination of loop diuretics and aminoglycosides. Ototoxicity depends upon several factors in addition to age, including patient population, dose and duration of therapy, genetic and pharmacokinetic factors, and the particular aminoglycoside used. The molecular mechanisms of developmental hypersensitivity have not yet been determined.