Efficacy and Tolerability of Extended-Interval Aminoglycoside Administration in Pediatric Patients

Abstract

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.

Once-daily intramuscular amikacin for outpatient treatment of lower urinary tract infections caused by extended-spectrum &beta;-lactamase-producing <em>Escherichia coli</em> in children

“…Amikacin monotherapy seems to be a useful alternative for the outpatient treatment of children with uncomplicated ESBL UTIs because of its high urinary excretion (aminoglycosides reach concentrations in the urine 25–100-fold that of serum), low resistance rates, easy intramuscular administration, and low cost. 5 , 8 , 16 Certain pharmacodynamic and kinetic properties of the aminoglycosides are important for their clinical application. 27 Aminoglycosides demonstrate both concentration-dependent killing and post-antibiotic effect that allow a once-daily administration schedule.…”

“… 14 , 15 Ototoxicity was defined as any symptoms or signs of the following after amikacin use: nausea, vomiting, nystagmus, ataxia, dizziness, vertigo, tinnitus or hearing loss. 16 Monitoring of ototoxicity was made by the subjective patient assessment at outpatient clinic visits.…”

Population Pharmacokinetics of Gentamicin and Dosing Optimization for Infants

“…In fact, the maximum concentration of drug in serum (C max ) should not be measured until 2 h after a 30-min infusion to ensure postdistributional samples in 7 mg/kg once-daily dosing (21). Despite the postantibiotic effect, trough serum concentrations of Ͻ0.5 mg/liter should not last for Ͼ6 to 8 h in order to ensure the optimal efficacy of this antibiotic (13,14,16,32). Figure 4 shows the mean gentamicin plasma concentrations and 5th to 95th percentiles corresponding to 1,000 simulations obtained for the final two-compartment model, as generated by NONMEM and using data obtained from a standard 6-month-old infant weighing 8 kg, having a CR S of 0.4 mg/dl, and receiving 7 mg/kg/24 h of intravenous gentamicin.…”

Extended‐Interval Once‐Daily Dosing of Aminoglycosides in Adult and Pediatric Patients with Cystic Fibrosis

“…3 Once-daily EID is more convenient and may provide a better quality of life for patients with cystic fibrosis who attend school or work full-time, and it may be more cost-effective than traditional dosing by decreasing nursing and pharmacy preparation time. [4][5][6] The treatment of a cystic fibrosis respiratory exacerbation consists of aggressive pulmonary physiotherapy and pharmacotherapy to alleviate obstruction and mitigate infection with colonizing bacteria such as Pseudomonas aeruginosa. These patients require multiple courses of aminoglycosides for an extended duration over the course of their For reprints, visit http://www.atypon-link.com/PPI/loi/phco.…”