Artificial intelligence and precision medicine: a pilot study predicting optimal ceftaroline dosage for pediatric patients

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Background Accurate drug dosing in pediatrics is complicated by age-related physiological variability. Standard weight-based dosing may result in either subtherapeutic exposure or toxicity. Machine learning (ML) models can capture complex relationships among clinical variables and support individualized therapy. Methods We analyzed clinical and pharmacokinetic data from 20 pediatric patients enrolled in the PUERI study (January 2020–November 2021, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy). Eight ML models-including linear regression (LR), ridge regression (RR), lasso regression (LaR), Huber regression (HR), random forest (RF), XGBoost, LightGBM, and a neural network (MLP)-were trained to predict ceftaroline doses that would achieve plasma concentrations close to the therapeutic target of 10 mg/L. Model performance was evaluated using mean absolute error (MAE), root mean squared error (RMSE), and the coefficient of determination (R 2 ). To ensure interpretability, we applied local interpretable model-agnostic explanations (LIME) to identify the most influential predictors of dose. Results MLP (MAE 1.53 mg, R 2 0.94) and XGBoost (MAE 2.04 mg, R 2 0.89) outperformed linear models. Predicted doses were more frequently aligned with therapeutic concentrations than those clinically administered. Model-based simulated concentrations fell within the therapeutic range in approximately 85% of cases, and the best ML models showed over 90% patient-level clinical. RF, LightGBM and XGBoost achieved the highest clinical alignment, with 94.2, 92.4 and 91.5% of patients reaching therapeutic levels. Renal function markers, such as serum creatinine and azotemia, together with anthropometric parameters including weight, height, and body mass index, were consistently the most influential features. Conclusion Advanced ML models can optimize ceftaroline dosing in pediatric patients and outperform traditional dosing strategies. Combining predictive accuracy with interpretability (via LIME) supports clinical trust and may enhance precision antibiotic therapy while reducing the risks of antimicrobial resistance and toxicity.

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