An Evaluation of Gentamicin, Tobramycin, and Amikacin Pharmacokinetic/Pharmacodynamic Parameters in HIV-Infected Children

Abstract

The purpose of the study was to calculate gentamicin, tobramycin, and amikacin pharmacokinetic parameters in HIV-infected children and compare conventional multiple daily aminoglycoside dosing to once-daily aminoglycoside (ODA) dosing in attaining peak serum aminoglycoside concentrations (SACs) to minimum inhibitory concentration for 90% of isolates (MIC(90)) ratios ≥8 against selected pathogens. Patients (<13yrs) receiving an aminoglycoside (15 patients/drug) in the treatment of gram-negative infection were studied. Intravenous gentamicin/ tobramycin were administered at a dose of 6-7.5 mg/kg/day and amikacin at 20-30 mg/kg/d divided every 8 hrs. Peak and trough serum concentrations were obtained and pharmacokinetic parameters were calculated utilizing a one-compartment steady-state model. SACs for gentamicin/tobramycin dosed at 7.5 mg/kg and amikacin at 22.5 mg/kg once daily were simulated using the calculated pharmacokinetic parameters. Peak SAC:MIC(90) ratios were calculated for each dosing method. Mean pharmacokinetic parameters were within 1 standard deviation of reported literature values. Mean peak:MIC(90) ratio of ≥8 was attained only for Klebsiella species (MIC90 1 μg/mL) using conventional gentamicin/tobramycin dosing whereas mean amikacin peak:MIC(90) ratios ≥8 were reached for Klebsiella, Enterobacter, and Citrobacter species (MIC(90) 4 μg/mL). ODA simulations predicted gentamicin/tobramycin peak:MIC(90) ratios ≥8 in 100% of patients with an organism-MIC(90) of 1 μcg/mL and in 80% of patients with an organism-MIC(90) of 2 μg/mL. Amikacin peak:MIC(90) ratio ≥8 was predicted for 93% of patients with an organism-MIC(90) of 4 μg/mL but in only 27% if the MIC(90) was 8 μg / mL. Optimal peak SAC:MIC90 ratios using conventional aminoglycoside dosing were predicted only for organisms with low MIC(90) values. ODA dosing represents an option for improving pharmacodynamic outcomes.