In silico Evaluation of a Vancomycin Dosing Guideline Among Adults with Serious Infections

Abstract

Background: This study aimed to compare the achievement of pharmacokinetic–pharmacodynamic (PK-PD) exposure targets for vancomycin using a newly developed dosing guideline with product-information-based dosing in the treatment of adult patients with serious infections. Methods: In silico product-information- and guideline-based dosing simulations for vancomycin were performed across a range of doses and patient characteristics, including body weight, age, and renal function at 36–48 and 96 hours, using a pharmacokinetic model derived from a seriously ill patient population. The median simulated concentration and area under the 24-hour concentration–time curve (AUC0-24) were used to measure predefined therapeutic, subtherapeutic, and toxicity PK-PD targets. Results: Ninety-six dosing simulations were performed. The pooled median trough concentration target with guideline-based dosing at 36 and 96 hours was achieved in 27.1% (13/48) and 8.3% (7/48) of simulations, respectively. The pooled median AUC0-24/minimum inhibitory concentration ratio with guideline-based dosing at 48 and 96 hours was attained in 39.6% (19/48) and 27.1% (13/48) of simulations, respectively. Guideline-based dosing simulations yielded improved trough target attainment compared with product-information-based dosing at 36 hours and significantly less subtherapeutic drug exposure. The toxicity threshold was exceeded in 52.1% (25/48) and 0% (0/48) for guideline- and product-information-information-based dosing, respectively (P < 0.001). Conclusions: A Critical care vancomycin dosing guideline appeared slightly more effective than standard dosing, as per product information, in achieving PK-PD exposure associated with an increased likelihood of effectiveness. In addition, this guideline significantly reduced the risk of subtherapeutic exposure. The risk of exceeding toxicity thresholds, however, was greater with the guideline, and further investigation is suggested to improve dosing accuracy and sensitivity.