Design and prospective validation of a dosing instrument for continuous infusion of vancomycin: a within-population approach.

Introduction: The clinical application of continuous infusion (CoI) of vancomycin has gained interest in recent years. Since no international guidelines on initial dosing of vancomycin CoI exist, there is a need for methods to facilitate the switch from intermittent to continuous vancomycin dosing algorithms in clinically infected populations. Therefore, the aim of this study was to design and validate an a priori dosing schedule for CoI of vancomycin in clinical practice.

Methods: A dosing table for CoI of vancomycin based on estimated glomerular filtration rate (eGFR) was developed by simulation of continuous infusion of vancomycin using pharmacokinetic (PK) software and a PK population model designed from historical within-population data in intermittently dosed patients. The target range for the first vancomycin serum concentrations drawn approximately 24 h after start of infusion' (C24) was set at 15-20 mg/L corresponding with an area under the curve (AUC) of at least 350 mg·h·L(-1). The performance of the dosing schedule was primarily assessed by describing the percentages of patients attaining the predefined target.

Results: An eGFR-derived dosing schedule for CoI of vancomycin was established and implemented in clinical practice. Prospective assessment in 35 general ward and 45 intensive care unit patients showed that the C24 target was reached in 69 and 63 % and the AUC target was attained in 80 and 72 % of patients, respectively.

Conclusions: An easy method to design and validate an eGFR-derived dosing algorithm for the continuous infusion of vancomycin to switch from intermittent to continuous dosing of vancomycin was developed.