Population pharmacokinetics and clinical outcomes of polymyxin B in paediatric patients with multidrug-resistant Gram-negative bacterial infections

Abstract

Abstract Background Current polymyxin B dosing in children relies on scant data. Objectives To build a population pharmacokinetic (PK) model for polymyxin B in paediatric patients and assess the likely appropriateness of different dosages. Methods A total of 19 paediatric patients were enrolled to receive intravenous polymyxin B (1.33–2.53 mg/kg/day), and the median age was 12.5 (range 3.2–17.8) years. Serial plasma samples were collected at steady-state and modelled by population PK analysis. Clinical efficacy and nephrotoxicity of polymyxin B treatment were also assessed. Results PK data were adequately described by a two-compartment model with first-order elimination, and weight was a significant covariate of polymyxin B clearance. Clinical success occurred in 14 of 19 patients (73.7%) and only one patient developed acute kidney injury. The 28 day mortality was 10.5% (2/19). The steady-state polymyxin B exposure was 36.97 ± 9.84 mg·h/L, lower than the therapeutic exposure of 50–100 mg·h/L. With the AUC24h/MIC target of 50, the dosage of 1.5–3.0 mg/kg/day had a probability of target attainments over 90% when MICs were <0.5 mg/L. Conclusions Dose adjustment of polymyxin B needs to consider the MIC of infecting pathogens. Current polymyxin B dosing for paediatric patients may be acceptable when MICs are <0.5 mg/L.