Aminoglycoside toxicity in infants and children

Abstract

The aminoglycosides are frequently prescribed for infants and children, especially newborn infants with suspected or documented sepsis or meningitis. In older infants and children, the aminoglycosides are commonly used to treat acute respiratory exacerbations in patients with cystic fibrosis, intra-abdominal sepsis, complicated urinary tract infections, and other infections caused by gram-negative enteric bacilli. Although these drugs are generally well tolerated and efficacious, there is relatively little information on toxicity in pediatric patients. The potential for ototoxicity from the aminoglycosides, especially streptomycin, kanamycin, and gentamicin, was evaluated in seven prospective, controlled studies of 1,321 newborn infants. Although the designs and follow-up periods were different among the studies, the audiometric tests were similar and appropriate for age. Three studies measured auditory brain stem response during the neonatal and early infancy periods. With the exception of one study, ototoxicity occurred less frequently in aminoglycoside-treated patients than it did in untreated control patients. One study from Canada demonstrated abnormal brain stem response audiograms in gentamicin- or tobramycin-treated neonates compared with normal brain stem response audiograms in untreated control subjects. That study, however, was flawed by the small number of patients evaluated and the lack of follow-up of any patients. Nephrotoxicity appears to be rare in neonates, although one study in this age group showed an elevated N-acetyl-beta-glucosaminidase excretion rate in gentamicin-treated infants compared with rates in infants treated with amikacin or chloramphenicol. In that study, no attempt was made to correlate lysosomal injury with clinical or conventional laboratory evidence of nephrotoxicity. The toxicity of the aminoglycosides in older infants and children has not been adequately assessed. The broadest experience with these compounds has been in patients with cystic fibrosis, and most open studies in these patients have indicated a relative lack of ototoxicity and nephrotoxicity. It should be emphasized, however, that the standard dosage of aminoglycosides in patients with cystic fibrosis frequently results in serum concentrations that are lower than anticipated because of a relatively larger volume of drug distribution and a greater urinary excretion rate. The lack of reports on aminoglycoside-associated toxic effects in children suggests that these compounds are safe and well tolerated in this age group.