PURPOSE: Better dosing is needed for antibiotics, including teicoplanin (TEI), to prevent emergence of resistant bacterial strains. Here, we assess the TEI pharmacokinetics (PK) related to a 10 mg/l minimum inhibitory concentration (MIC) target in ICU children (4 to 120 months; n = 20) with gram+ infections. METHODS: Standard administration of TEI was with three 10 mg/kg Q12h, loading infusions, and maintainance with 10 mg/kg or 15 mg/kg Q24h. During maintenance, 9 samples (3/day) were collected per patient and the PK analyzed with Nonlinear Mixed Effects Model (NONMEM). RESULTS: Thirty-five percent of concentrations in older children (> or =2 months) vs. 8% in younger infants (<12 months) were below the target MIC. The global bicompartmental population PK parameters were [mean (interindividual CV%)] CL = 0.23 l/h [72%], V = 3.16 l [58%], k12 = 0.23 h(-1), and k21 = 0.04 h(-1). Two PK subpopulations were identified. The older children had CL = 0.29 [23%] l/h, V = 3.9 l and the younger infants, CL = 0.09 [37%] l/h, V = 1.05 l. Residual error was reduced from 52% to around 30% in the final models. CONCLUSIONS:Older children in the ICU may require relatively higher doses of teicoplanin. However, a study in a larger population is needed.
RCT Entities:
PURPOSE: Better dosing is needed for antibiotics, including teicoplanin (TEI), to prevent emergence of resistant bacterial strains. Here, we assess the TEI pharmacokinetics (PK) related to a 10 mg/l minimum inhibitory concentration (MIC) target in ICU children (4 to 120 months; n = 20) with gram+ infections. METHODS: Standard administration of TEI was with three 10 mg/kg Q12h, loading infusions, and maintainance with 10 mg/kg or 15 mg/kg Q24h. During maintenance, 9 samples (3/day) were collected per patient and the PK analyzed with Nonlinear Mixed Effects Model (NONMEM). RESULTS: Thirty-five percent of concentrations in older children (> or =2 months) vs. 8% in younger infants (<12 months) were below the target MIC. The global bicompartmental population PK parameters were [mean (interindividual CV%)] CL = 0.23 l/h [72%], V = 3.16 l [58%], k12 = 0.23 h(-1), and k21 = 0.04 h(-1). Two PK subpopulations were identified. The older children had CL = 0.29 [23%] l/h, V = 3.9 l and the younger infants, CL = 0.09 [37%] l/h, V = 1.05 l. Residual error was reduced from 52% to around 30% in the final models. CONCLUSIONS: Older children in the ICU may require relatively higher doses of teicoplanin. However, a study in a larger population is needed.
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