Pharmacokinetics of Teicoplanin in An ICU Population of Children and Infants

Abstract

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. 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). 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. Older children in the ICU may require relatively higher doses of teicoplanin. However, a study in a larger population is needed.