Population Pharmacokinetics and Pharmacodynamic Target Attainment of Vancomycin in Neonates on Extracorporeal Life Support

Pediatr Crit Care Med. 2017 Oct;18(10):977-985. doi: 10.1097/PCC.0000000000001250.


Objectives: To evaluate the population pharmacokinetics and pharmacodynamic target attainment of vancomycin in neonates with a contemporary ¼-inch extracorporeal life support circuit with a Quadrox-iD Pediatric oxygenator (Maquet Cardiovascular, LLC, Wayne, NJ).

Design: Retrospective medical record review.

Setting: Two free-standing tertiary/quaternary pediatric children's hospitals.

Patients: Neonates receiving either veno-arterial or veno-venous extracorporeal life support and vancomycin for empiric or definitive therapy with resulting serum concentrations.

Interventions: None.

Measurements and main results: Twelve patients with a median gestations age of 39 weeks (range 36-41 wk) and a median postnatal age of 9.5 days (range 0-28 d) accounted for 14 courses of vancomycin therapy while on extracorporeal life support and were included in the analysis. The median weight was 3.1 kg (range 2.2-4.41 kg) with five of 12 patients (41.7%) being female. Vancomycin concentrations were best described by an one-compartment model incorporating allometric scaling of estimated glomerular filtration rate on clearance. The mean total body clearance (mL/min/kg) for the population was 3.48 ± 1.31 mL/min/kg, and the mean total volume of distribution (L/kg) for the population was 1.2 ± 0.4 L/kg. The intermittent and continuous infusion dosing regimens that provided for the highest percentage of trough concentrations in the range of 10-20 mg/L were the 10 mg/kg/dose IV q8h, 12.5 mg/kg/dose IV q8-12h, 15 mg/kg/dose IV q12h, and 20 mg/kg/dose IV q12h, and the 20, 25, and 30 mg/kg/d continuous infusion regimens, respectively. All regimens allowed for an area under the concentration:minimum inhibitory concentration ratio of 400:1 for minimum inhibitory concentrations of less than or equal to 0.5 mg/L for a 90% PTA. None of the simulated regimens had a greater than 90% probability of achieving an area under the concentration:minimum inhibitory concentration ratio of 400:1 for vancomycin minimum inhibitory concentrations greater than or equal to 1 mg/L while maintaining trough concentrations in the range of 10-20 mg/L.

Conclusions: To our knowledge, this is the first pharmacokinetic and pharmacodynamic study of neonates receiving vancomycin with a contemporary ¼-inch extracorporeal life support circuit including the Quadrox-iD Pediatric oxygenator (Maquet Cardiovascular, LLC). The data suggest differences in vancomycin pharmacokinetics compared with previous extracorporeal life support data, notably a more rapid clearance, which could result in lower vancomycin concentrations. Considering this, a more aggressive initial dosing regimen may need to be employed in infants on extracorporeal life support.

MeSH terms

  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / therapeutic use
  • Area Under Curve
  • Drug Administration Schedule
  • Extracorporeal Membrane Oxygenation* / instrumentation
  • Extracorporeal Membrane Oxygenation* / methods
  • Female
  • Gram-Positive Bacterial Infections / blood
  • Gram-Positive Bacterial Infections / drug therapy*
  • Humans
  • Infant, Newborn
  • Male
  • Metabolic Clearance Rate
  • Microbial Sensitivity Tests
  • Monte Carlo Method
  • Retrospective Studies
  • Vancomycin / blood
  • Vancomycin / pharmacokinetics*
  • Vancomycin / therapeutic use


  • Anti-Bacterial Agents
  • Vancomycin