Article Text
Abstract
Background Current paediatric vancomycin (VANC) dose regimens recommend 40–60 mg/kg bodyweight/day in 3–4 doses, adjusted according trough values (optimum range 10–20 mg/L). Often, multiple dose escalations over several days after the start of treatment are needed to obtain appropriate levels.
Purpose To evaluate the current dosing scheme (4 × 15 mg/kg) against the optimal pharmacokinetic/pharmacodynamic parameters for VANC (AUC/MIC ≥ 400) and trough levels.
Material and methods Setting: a paediatric ward in a tertiary care university hospital. Patients >1 year and <18 years receiving intermittent VANC infusions between 2011 and 2013 were included. All necessary data were obtained from the electronic patient files. VANC clearance and Area Under the Curve (AUC) were obtained using JPKD software (Kaoshiung Medical University–Taiwan) using a 1-compartment, first-order kinetic Bayesian analysis. The Minimum Inhibitory Concentration (MIC) was set to 1 mg/L according EUCAST recommendations. For analysis, patients were stratified according age: <6; 6–12; and >12 years. Statistical analysis was done using SPSS 22.0.
Results Twenty-four patients (21 haematological; median age 6.3 years) were included with 183 available trough levels. VANC clearance was correlated with total administered fluid (ρ = 0.410, p < 0.0001) and excreted fluid (ρ = 0.368, p < 0.0001); and inversely correlated with age (ρ = -0.624; p < 0.0001); and weight (ρ = -0.616, p < 0.0001). Agreement between suitable trough levels and AUC/MIC was 86.0%. To obtain AUC/MIC ≥400, the required median dose was 29.36 mg/kg 4× daily for children <6 year; 21.52 mg/kg for 6–12 years; and 13.95 mg/kg >12 years (p < 0.0001). Similar median dosing values (24.89 mg/kg, 20.83 mg/kg and 13.95 mg/kg respectively) were needed when considering suitable trough values.
Conclusion Current paediatric vancomycin dose recommendations are insufficient and should take the patient’s age more into account. In order to quickly obtain appropriate levels, we propose the following daily dosing scheme: <6 years: 4 × 25–30 mg/kg; 6–12 years: 4 × 20 mg/kg; >12 years: 4 × 15 mg/kg/day. A larger prospective study will be needed to confirm the recommended paediatric vancomycin dose regimen.
References and/or acknowledgements No conflict of interest.