Therapeutic drug monitoring of liposomal amphotericin B in children. Are we there yet? A systematic review

Introduction: Therapeutic drug monitoring (TDM) is a tool that supports personalized dosing, but its role for liposomal amphotericin B (L-amb) is unclear. This systematic review assessed the evidence for L-amb TDM in children. Objectives: To evaluate the concentration-efficacy relationship, concentration-toxicity relationship and pharmacokinetic/pharmacodynamic (PK/PD) variability of L-amb in children. Methods: We systematically reviewed PubMed and Embase databases following PRISMA guidelines. Eligible studies included L-amb PK/PD studies in children aged 0-18 years. Review articles, case series of Results In total, 4220 studies were screened; 6 were included, presenting data on 195 children. Invasive candidiasis and aspergillosis were the two most common infections treated with L-amb. Studies showed significant PK variability due to age (mean age ranged from 14 days to 17 years), body weight, non-linear PK and changes in the volume of distribution. Limited evidence supported a peak concentration/MIC (C-max/MIC) of 25-50 for optimal efficacy and an AUC(24) of >600 mg center dot h/L for nephrotoxicity. L-amb doses of 2.5-10 mg/kg/day were reported to achieve C-max/MIC > 25 using an MIC of 1 mg/L. Conclusions: While significant PK variability was observed in children, evidence to support routine L-amb TDM was limited. Further studies on efficacy and toxicity benefits are required before routine TDM of L-amb can be recommended.