Population pharmacokinetic analysis of teicoplanin in paediatric patients, including those receiving continuous kidney replacement therapy: a prospective cohort study.

Abstract

Objectives: Teicoplanin is a commonly used antibiotic in critically ill children. However, teicoplanin dosing is often inaccurate, especially in children undergoing continuous kidney replacement therapy (CKRT). This study aims to develop a population pharmacokinetic (PK) model to optimize teicoplanin dosing in critically ill children, including those on CKRT.

Methods: Data from 26 critically ill children (12 with CKRT) receiving the standard dosing regimen were analysed. In total, 172 teicoplanin concentration measurements from plasma, pre- and post-filter ports were modelled simultaneously using NONMEM 7.4. Simulations were conducted to assess the target attainment (Cmin = 10 mg/L and AUC24/MIC > 800 h) of the current standard dosing regimen and of different alternative dosing regimens.

Results: A two-compartment model was selected. Weight significantly affected renal clearance and volume of distribution of the central compartment, while filter surface area affected haemofilter clearance. Only 16 patients (59%) achieved a Cmin of >10 mg/L with the standard dosing regimen, and only 1 achieved the target AUC/MIC. Based on simulation results, 3 × 15 mg/kg q12h + 10 mg/kg q24h (CKRT) and 3 × 15 mg/kg q12h + 15 mg/kg q24h (no CKRT) could be better alternative regimens.

Conclusions: This population model is a good proof of concept to develop modelling approaches that could help in an individualized dosing approach that needs to be adopted in critically ill paediatric patients. The standard paediatric dosage for teicoplanin could be insufficient for optimal exposure, and higher doses may benefit both CKRT and non-CKRT patients.