Vancomycin trough concentration in adult patients with periprosthetic joint infection: A machine learning-based covariate model

Br J Clin Pharmacol. 2024 Sep;90(9):2188-2199. doi: 10.1111/bcp.16112. Epub 2024 Jun 6.

Abstract

Aims: Although there are various model-based approaches to individualized vancomycin (VCM) administration, few have been reported for adult patients with periprosthetic joint infection (PJI). This work attempted to develop a machine learning (ML)-based model for predicting VCM trough concentration in adult PJI patients.

Methods: The dataset of 287 VCM trough concentrations from 130 adult PJI patients was split into a training set (229) and a testing set (58) at a ratio of 8:2, and an independent external 32 concentrations were collected as a validation set. A total of 13 covariates and the target variable (VCM trough concentration) were included in the dataset. A covariate model was respectively constructed by support vector regression, random forest regression and gradient boosted regression trees and interpreted by SHapley Additive exPlanation (SHAP).

Results: The SHAP plots visualized the weight of the covariates in the models, with estimated glomerular filtration rate and VCM daily dose as the 2 most important factors, which were adopted for the model construction. Random forest regression was the optimal ML algorithm with a relative accuracy of 82.8% and absolute accuracy of 67.2% (R2 =.61, mean absolute error = 2.4, mean square error = 10.1), and its prediction performance was verified in the validation set.

Conclusion: The proposed ML-based model can satisfactorily predict the VCM trough concentration in adult PJI patients. Its construction can be facilitated with only 2 clinical parameters (estimated glomerular filtration rate and VCM daily dose), and prediction accuracy can be rationalized by SHAP values, which highlights a profound practical value for clinical dosing guidance and timely treatment.

Keywords: SHAP; covariate model; machine learning; periprosthetic joint infection; vancomycin trough concentration.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / blood
  • Anti-Bacterial Agents* / pharmacokinetics
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Machine Learning*
  • Male
  • Middle Aged
  • Models, Biological
  • Prosthesis-Related Infections* / drug therapy
  • Retrospective Studies
  • Vancomycin* / administration & dosage
  • Vancomycin* / blood
  • Vancomycin* / pharmacokinetics

Substances

  • Vancomycin
  • Anti-Bacterial Agents