Towards precision dosing of vancomycin in patients with allogeneic hematopoietic stem cell transplantation: a comparison of published population pharmacokinetic models.

Abstract

Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) often receive vancomycin as antibiotic treatment using therapeutic drug monitoring (TDM). TDM can be performed using a Bayesian approach, where concentration measurements are supported by a previously developed pharmacokinetic model based on a population as similar as possible to the treated patient. As a model developed in a similar population is not always available, it must be ensured that the predictive performance is not compromised. We retrospectively collected data from 121 adult allo-HSCT patients who received vancomycin treatment including trough concentration TDM between January and December 2021. Predictive performance of 21 published pharmacokinetic models was assessed by comparing the third observed vancomycin concentration per patient with the corresponding model prediction. Prediction was based on covariates alone (a priori) or covariates and TDM measurements (Bayesian). Predictive performance was quantified by a median prediction error (MPE) for accuracy and median absolute prediction error (MAPE) for precision. MPE ranged between -199.6% and 93.3% (a priori) and between -50.6% and 19.1% (Bayesian), while MAPE ranged between 31.6% and 199.6% (a priori) and between 19.8% and 53.5% (Bayesian). The Okada et al. model was one of the most accurate and precise models in the a priori (MPE: -4%; MAPE: 31.6%) and Bayesian scenario (MPE: -6.9%; MAPE: 19.8%). The model published by Okada et al. was developed in allo-HSCT patients. That may explain the high predictive performance, especially in the a priori scenario. We recommend the Okada et al. model for future TDM in allo-HSCT patients.