50 Years Ago in The Journal of Pediatrics:

Article Outline

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Yow M, et al. J Pediatr 1962;60:230-42

This report was published 3 years after kanamycin became available. As noted by the authors, kanamycin had proven to be an effective drug for the treatment of serious infections. However, because of similarities in chemical structure to streptomycin and neomycin, drugs known to be ototoxic and nephrotoxic, the potential for serious side effects was acknowledged. Yow et al performed hearing testing on 30 children who received kanamycin therapy for 5 or more days. None had known risk factors for hearing loss, but all were seriously ill. Dosages of kanamycin varied widely, and 5 infants received other ototoxic drugs. Sensorineural hearing loss was diagnosed in 5 of the 30 infants (17%) treated with kanamycin. All of these infants had potential confounders that might have increased risk of hearing loss; 1 child received other ototoxic drugs, 1 had Haemophilus influenza meningitis and otitis media, 1 was thought to have emboli to cerebral vessels, and 2 were preterm, very low birth weight infants, 1 of whom received very high doses of kanamycin. Three of the 5 children with hearing loss had impaired renal function at the time of therapy. Thirty children without exposure to kanamycin were studied as controls; 3 were found to have hearing loss.

This study demonstrates the importance of postmarketing surveillance for adverse outcomes for any new drug, with the understanding of risk profiles of similar drugs. The study also serves as a reminder that use of any drug must be considered carefully, with an understanding of severity of illness, specific indications, known side effects, and consideration of other agents that might be safer but equally effective. The importance of routine childhood immunizations is highlighted by the patient with H influenza meningitis, a serious illness with high risk of morbidity and mortality that is largely a disease of the past in the United States, thanks to the widespread use of Hib conjugate vaccine.

Since this article was published almost 50 years ago, much has been learned about aminoglycoside pharmacokinetics, the importance of monitoring drug levels, and the pathophysiology and risk factors for drug-associated hearing loss. A number of genetic mutations have been identified that increase risk of aminoglycoside-associated hearing loss. Perhaps most importantly, there is now widespread awareness of the impact of hearing impairment on child development, particularly on speech, language, and cognitive development. The American Academy of Pediatrics recommends universal hearing screening during the first 3 months of life, and today more than 95% of infants are screened.