Efficacy and tolerability of extended-interval aminoglycoside administration in pediatric patients.

Aminoglycosides are commonly used to treat serious Gram-negative infections in pediatric patients. An effort to improve the efficacy and tolerability of this antibiotic class has led to evaluation of extended-interval aminoglycoside administration (EIAA). EIAA is designed to achieve higher peak plasma aminoglycoside concentrations, with relatively undetectable trough concentrations, when compared with conventional aminoglycoside administration (CAA), and is therefore expected to be markedly effective and to reduce drug accumulation and prevent nephrotoxicity and ototoxicity. Clinical trials evaluating EIAA in neonates included patients with suspected Gram-negative infections requiring short courses of aminoglycoside therapy. Consequently, comparative efficacy of EIAA versus CAA could not be assessed. In addition, ototoxicity was often not assessed, and nephrotoxicity was virtually undetectable. Similarly, trials evaluating EIAA versus CAA in infants and children have not demonstrated a difference in outcomes. The use of EIAA in children with febrile neutropenia has been evaluated primarily with amikacin. The incidences of nephrotoxicity and ototoxicity were low, and were similar between EIAA and CAA. No deaths were reported in any of these studies; however, this could be related to the inclusion of patients with undocumented bacteremia. Further investigation of EIAA is necessary in patients with documented bacteremia, since plasma aminoglycoside concentrations were undetectable for most of the dosage interval in children with febrile neutropenia who were treated once daily. Overall, clinical studies suggest that EIAA has similar efficacy to, and no higher risk of toxicity than, CAA in neonates, infants, and children. A few evaluations have also demonstrated that EIAA is cost-effective in neonates and in children with febrile neutropenia. Future studies evaluating the efficacy and tolerability of EIAA in pediatric patients with documented systemic infections should be prospective, randomized, controlled trials with sample sizes sufficient to detect differences between administration methods. Further evaluations should also address the optimal dosage and cost-effectiveness of EIAA in infants and children.