Related Experiment Video
Updated: Mar 9, 2026
Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
Published on: October 25, 2013
Impact of vancomycin protein binding on target attainment in critically ill children: back to the drawing board?
Pieter A J G De Cock1,2,3, Sarah Desmet1,2, Annick De Jaeger3
1Department of Pharmacy, Ghent University Hospital, Ghent, Belgium.
Insights
Vancomycin protein binding is lower and more variable in critically ill children. Using unbound concentrations improves pharmacokinetic/pharmacodynamic target attainment, suggesting protein binding assessment is crucial for optimizing vancomycin therapy.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Pediatrics
Background:
- Vancomycin is a critical antibiotic for treating serious Gram-positive infections.
- Understanding vancomycin's pharmacokinetic/pharmacodynamic (PK/PD) properties is essential for effective dosing, especially in vulnerable populations like critically ill children.
- Plasma protein binding significantly influences drug distribution and efficacy, but data in pediatric intensive care unit (PICU) patients are limited.
Purpose of the Study:
- To investigate the extent and variability of plasma protein binding of vancomycin in critically ill children.
- To evaluate the target attainment rates of vancomycin therapy using both total and unbound concentrations in this population.
- To develop a predictive model for unbound vancomycin concentrations.
Main Methods:
- An observational study involving 32 critically ill pediatric patients receiving vancomycin.
- Collection and analysis of 188 plasma samples to determine vancomycin concentrations and protein binding.
- Linear mixed model analysis to identify covariates affecting unbound vancomycin fraction and concentration.
- Evaluation of pharmacokinetic/pharmacodynamic (PK/PD) target attainment using established indices.
Main Results:
- The unbound vancomycin fraction was highly variable (median 71.1%) and lower than reported in non-critically ill adults.
- Total vancomycin trough concentrations met targets in only 8% of patients.
- Higher target attainment rates were observed using unbound concentrations (fAUC/MIC ≥200 achieved in 83% of patients).
- A validated equation was developed to predict unbound vancomycin concentrations based on total vancomycin and total protein levels.
Conclusions:
- Vancomycin exhibits significant and variable protein binding in critically ill children, necessitating consideration of unbound concentrations for therapeutic drug monitoring.
- Pharmacokinetic/pharmacodynamic (PK/PD) target attainment is substantially improved when utilizing unbound vancomycin concentrations compared to total concentrations.
- Protein binding assessment should be integrated into future vancomycin PK/PD research and clinical practice in pediatric critical care to optimize treatment outcomes.
Objectives:
The objectives of this observational study were to investigate plasma protein binding and to evaluate target attainment rates of vancomycin therapy in critically ill children.
Patients And Methods:
Paediatric ICU patients, in whom intravenous intermittent dosing (ID) or continuous dosing (CD) with vancomycin was indicated, were included. Covariates on unbound vancomycin fraction and concentration were tested using a linear mixed model analysis and attainment of currently used pharmacokinetic/pharmacodynamic (PK/PD) targets was evaluated. Clinicaltrials.gov: NCT02456974.
Results:
One hundred and eighty-eight plasma samples were collected from 32 patients. The unbound vancomycin fraction (median = 71.1%; IQR = 65.4%-79.7%) was highly variable within and between patients and significantly correlated with total protein and albumin concentration, which were both decreased in our population. Total trough concentration (ID) and total concentration (CD) were within the aimed target concentrations in 8% of patients. The targets of AUC/MIC ≥400 and f AUC/MIC ≥200 were achieved in 54% and 83% of patients, respectively. Unbound vancomycin concentrations were adequately predicted using the following equation: unbound vancomycin concentration (mg/L) = 5.38 + [0.71 × total vancomycin concentration (mg/L)] - [0.085 × total protein concentration (g/L)]. This final model was externally validated using 51 samples from another six patients.
Conclusions:
The protein binding of vancomycin in our paediatric population was lower than reported in non-critically ill adults and exhibited large variability. Higher target attainment rates were achieved when using PK/PD indices based on unbound concentrations, when compared with total concentrations. These results highlight the need for protein binding assessment in future vancomycin PK/PD research.
More Related Videos
Related Concept Videos
01:26Pharmacokinetics in Pediatric Patients: Drug Excretion
01:20Estimation of k and VD of Aminoglycosides
01:17Pharmacokinetics in Pediatric Patients: Drug Distribution
01:29Drug Distribution: Plasma Protein Binding
01:15Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations
01:29Factors Affecting Protein-Drug Binding: Patient-Related Factors
Age stands as a key determinant in protein-drug binding. Neonates, characterized by low albumin content, experience heightened concentrations of unbound drugs such as phenytoin and...