Vancomycin in Pediatric Patients with Cystic Fibrosis: Dose Optimization Using Population Pharmacokinetic Approach
Aysenur Yaliniz1,2, Mathieu Blouin3,4, Marie-Élaine Métras4,5
1STP2 Laboratory, Faculty of Pharmacy, Université de Montréal, 2940 Chemin de Polytechnique, Montreal, QC, H3T 1J4, Canada. aysenur.yaliniz@umontreal.ca.
Insights
Vancomycin dosing for pediatric cystic fibrosis (CF) patients needs careful monitoring. This study evaluated population pharmacokinetic (popPK) models to find optimal vancomycin regimens, highlighting the need for external validation before clinical use.
Area of Science:
- Pharmacology
- Pharmacometrics
- Pediatric Infectious Diseases
Background:
- Increasing Staphylococcus aureus infections in pediatric cystic fibrosis (CF) patients necessitate effective vancomycin treatment.
- Therapeutic drug monitoring (TDM) is crucial for vancomycin, with updated guidelines recommending Bayesian approaches using population pharmacokinetic (popPK) models.
- Evaluating existing vancomycin popPK models is essential for optimizing treatment in this vulnerable population.
Purpose of the Study:
- To assess the predictive performance of vancomycin popPK models in pediatric CF patients.
- To determine optimal initial vancomycin dosing regimens through simulations.
- To guide the clinical implementation of vancomycin TDM strategies.
Main Methods:
- Literature review to identify published vancomycin popPK models for pediatric CF patients.
- External evaluation of identified models using patient data from two Canadian centers.
- Simulations to determine optimal dosing regimens based on model performance.
Main Results:
- Only two relevant vancomycin popPK models were identified.
- External evaluation showed significant population bias (28.1%) and imprecision (33.7%).
- Re-estimation of parameters improved model performance, suggesting an optimal initial regimen of 15 mg/kg/dose every 6 hours.
Conclusions:
- The predictive performance of vancomycin popPK models varies based on the data used for evaluation.
- External validation is critical before adopting vancomycin popPK models in clinical practice.
- Optimal initial dosing regimens require careful consideration and validation through robust modeling.
Background:
An increase in Staphylococcus aureus infections has been reported in pediatric patients with cystic fibrosis (CF) over the last few years. This pathogen is commonly treated with vancomycin, an antibiotic for which therapeutic drug monitoring (TDM) is recommended. Updated guidelines were recently published regarding new targets of exposure for the TDM of vancomycin through a Bayesian approach, using population pharmacokinetic (popPK) models.
Objectives:
This study aims to assess the predictive performance of vancomycin popPK models in pediatric patients with CF and to recommend optimal initial dosing regimens based on simulations.
Methods:
Patient data were collected from two centers in Canada, and a literature review was conducted to identify all published vancomycin popPK models for pediatric CF patients. External evaluation and simulations were performed according to patient and occasion of treatment.
Results:
A total of 53 vancomycin concentrations were collected from six pediatric CF patients. Only two popPK models of vancomycin for pediatric CF patients were identified through the literature review. The external evaluation results for both centers combined revealed a population bias of 28.1% and an imprecision of 33.7%. A re-estimation of parameters was performed to improve predictive performance. The optimal initial dosing regimen was 15 mg/kg/dose administered every 6 hours according to the per occasion remodel.
Conclusion:
The predictive performance and identified optimal initial dosing regimens associated with the model were different depending on the data used, showing external evaluation's importance before implementing a model in clinical practice.
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