Journal article
Population Pharmacokinetics and Pharmacodynamic Target Attainment of Vancomycin in Neonates on Extracorporeal Life Support
Pediatric critical care medicine, v 18(10), pp 977-985
01 Oct 2017
PMID: 28650363
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Objectives: To evaluate the population pharmacokinetics and pharmacodynamic target attainment of vancomycin in neonates with a contemporary 1/4-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 1/4-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.
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Details
- Title
- Population Pharmacokinetics and Pharmacodynamic Target Attainment of Vancomycin in Neonates on Extracorporeal Life Support
- Creators
- Jeffrey J. Cies - Drexel UniversityWayne S. Moore - Product Innovation and Engineering (United States, Saint James) - LLCKristen Nichols - Riley Hosp Children, Indianapolis, IN USAChad A. Knoderer - Butler UniversityDominick M. Carella - St Christophers Hosp Children, Philadelphia, PA 19133 USAArun Chopra - Product Innovation and Engineering (United States, Saint James) - LLC
- Publication Details
- Pediatric critical care medicine, v 18(10), pp 977-985
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 9
- Grant note
- Merck; Merck & Company Allergan; AbbVie Thermo Fisher Scientific
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine
- Web of Science ID
- WOS:000412206900017
- Scopus ID
- 2-s2.0-85021262675
- Other Identifier
- 991019350598704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Critical Care Medicine
- Pediatrics