P0223 / #515: POPULATION PHARMACOKINETICS AND PHARMACODYNAMICS OF VANCOMYCIN AND MEROPENEM IN PEDIATRIC EXTRACORPOREAL MEMBRANE OXYGENATION SUPPORT (ECMO)

Aims & Objectives: Describe the population pharmacokinetics (PK) of vancomycin and meropenem in pediatric patients undergoing Extracorporeal Membrane Oxygenation Support (ECMO) as well as the achievement of therapeutic exposures. Methods: Prospective, multicentric, PK study including pediatric patients (1 month - fifteen years) receiving vancomycin and meropenem during ECMO support. Serial blood samples were collected, assayed and analyzed using a population PK approach using PMetrics. The target exposures for vancomycin was area under the curve/ minimum inhibitory concentration (MIC) ratio >400; and for meropenem concentrations >4 times MIC for at least 50% of dosing interval. MIC Pseudomonas aeruginosa 2 mcg/mL, MIC Staphylococcus aureus 1 mcg/mL. Results: Eleven patients were available for each antibiotic, male 45%, median age 4 years old (2 mth -13 y). The median estimated creatinine clearance was 178 (30-239) mL/min/1.73 m2. The median doses were 54 (20-60) mg/kg/day in 2-4 divided doses and 120 (60-120) mg/kg/day 2-3 divided doses for vancomycin and meropenem respectively. A two compartment model adequately described the data for both drugs. Weight and age were significant covariates for central volume of distribution and clearance (CL) for meropenem, respectively. Serum creatinine described CL for vancomycin. The PK parameter estimates were CL 0.94 ± 0.20 mL/kg/min and volume of distribution (Vd) 1.07 ± 0.12 L/kg for vancomycin and CL 3.79 ± 1.75 mL/kg/min and Vd 0.54 ± 0.12 L/kg for meropenem. For meropenem and vancomycin, 90% and 100% of patients achieved therapeutic exposures. Conclusions: Current dosing of meropenem and vancomycin was sufficient in this patient cohort.