Population Pharmacokinetics (PK) of Vanomycin (VAN) in Neonates on Extra-Corporeal Life Support

Learning Objectives: VAN remains first line therapy for the treatment of life-threatening infections caused by methicillin resistant Staphylococcus aureus (MRSA) and ampicillin resistant Enterococci. Current evidence suggests that VAN trough levels of 15–20 mg/L or an AUC:MIC ratio of 400:1 are needed to maximize outcomes. Many factors can affect VAN PK in the pediatric ICU including sepsis and ECLS. Currently, no VAN PK data exists for children on ECLS with the current ECLS equipment. The purpose of this study was to describe VAN PK in neonates with a contemporary ECLS operation, including the Quadrox-i neonatal oxygenator

Methods: During the ECLS run, routine blood samples were collected from 13 neonates who received VAN for either prophylaxis or empiric therapy. VAN concentrations were measured by fluorescent polarization and the population PK was determined using PMetrics. Multiple compartmental and covariate models were explored to determine the best fit of the data.

Results: 13 neonates with a median gestational age of 36 weeks accounted for 16 VAN treatment courses. Each course contributed a median of 8 VAN levels (3–27) to the model. A 2 compartment model with weight as a covariate fit the VAN concentration data the best. Mean (SD) population estimates for clearance (CL), volume of the central compartment (Vc), total volume of distribution (Vd), and intercompartment transfer constants were 1.93(5.11) mL/min/kg, 0.27(0.25) L/kg, 0.49 (0.38) L/kg, 2.49(1.4) h-1, and 2.64(1.1) h-1,

respectively. This resulted in a mean (SD) elimination half-life of 4.9(6.6) h. The CL estimate in this population of ECLS patients is significantly higher than previous estimates (0.5–1 mL/kg/min) with pre-Quadrox oxygenators with a similar Vd with a contemporary ECLS arrangement.

Conclusions: These are the first VAN PK data in neonates with a contemporary ECLS operation utilizing the Quadrox-i neonatal oxygenator demonstrating significantly higher CL values with a similar Vd.