Optimizing Initial Vancomycin Dosing in Hospitalized Patients Using Machine Learning Approach for Enhanced...

Vancomycin is commonly dosed using standard weight-based methods before dose adjustments are made through therapeutic drug monitoring (TDM). However, variability in initial dosing can lead to suboptimal therapeutic outcomes. A predictive model that personalizes initial dosing based on patient-specific pharmacokinetic factors prior to administration may enhance target attainment and minimize the need for subsequent dose adjustments.

This study aimed to develop and evaluate a machine learning (ML)-based algorithm to predict whether an initial vancomycin dose falls within the therapeutic range of the 24-hour area under the curve to minimum inhibitory concentration, thereby optimizing the initial vancomycin dosage.

A retrospective cohort study was conducted using hospitalized patients who received intravenous vancomycin and underwent pharmacokinetic TDM consultation (n=415). The cohort was randomly divided into training and testing datasets in a 7:3 ratio, and multiple ML techniques were used to develop an algorithm for optimizing initial vancomycin dosing. The optimal algorithm, referred to as the OPTIVAN algorithm, was selected and validated using an external cohort (n=268). We evaluated the performance of 4 ML models: gradient boosting machine, random forest (RF), support vector machine (SVM), and eXtreme gradient boosting (XGB). Additionally, a web-based clinical support tool was developed to facilitate real-time vancomycin TDM application in clinical practice.

The SVM algorithm demonstrated the best predictive performance, achieving an area under the receiver operating characteristic curve (AUROC) of 0.832 (95% CI 0.753-0.900) for the training dataset and 0.720 (95% CI 0.654-0.783) for the external validation dataset. The gradient boosting machine followed closely with AUROC scores of 0.802 (95% CI 0.667-0.857) for the training dataset and 0.689 (95% CI 0.596-0.733) for the validation dataset. In contrast, both XGB and RF exhibited relatively lower performance. XGB achieved AUROC values of 0.769 (95% CI 0.671-0.853) for the training set and 0.707 (95% CI 0.644-0.772) for the validation set, while RF recorded AUROC scores of 0.759 (95% CI 0.656-0.846) for the test dataset and 0.693 (95% CI 0.625-0.757) for the external validation set. The SVM model incorporated 7 covariates: age, BMI, glucose, blood urea nitrogen, estimated glomerular filtration rate, hematocrit, and daily dose per body weight. Subgroup analyses demonstrated consistent performance across different patient categories, such as renal function, sex, and BMI. A web-based TDM analysis tool was developed using the OPTIVAN algorithm.

The OPTIVAN algorithm represents a significant advancement in personalized initial vancomycin dosing, addressing the limitations of current TDM practices. By optimizing the initial dose, this algorithm may reduce the need for subsequent dosage adjustments. The algorithm's web-based app is easy to use, making it a practical tool for clinicians. This study highlights the potential of ML to enhance the effectiveness of vancomycin treatment.