Predicting tigecycline-related adverse events in infected patients: a machine learning approach with clinical
Shiya Wu1,2, Yuheng Chen3, Wenjie Fan4
1School of Pharmacy, Fujian Medical University, Fuzhou, China.
Background:
Tigecycline (TGC), while effective against multidrug-resistant infections, is limited by hepatotoxicity and coagulation disorders, yet lacks robust predictive tools.
Methods:
We developed an online dynamic nomogram to assess these adverse events using retrospective data from 2,553 TGC-treated patients (2020-2025). Seventy-seven clinical features were analyzed using Boruta and the Least Absolute Shrinkage and Selection Operator (LASSO) for feature selection. Seven machine learning (ML) models were evaluated via ten-fold cross-validation, as well as Receiver Operating Characteristic (ROC) curve and calibration curves, with SHapley Additive exPlanations (SHAP) analysis for interpretability and an online dynamic nomogram for clinical translation.
Results:
Logistic regression (LR) outperformed other algorithms, achieving Area Under the ROC Curve (AUC) values of 0.800 (95% CI: 0.727-0.874) for hepatotoxicity and 0.755 (95% CI: 0.665-0.845) for coagulation dysfunction. Independent risk factors for liver injury included prolonged treatment duration, high dosage, ICU admission, hepatitis B virus (HBV) infection, and elevated baseline levels of lactate dehydrogenase (LDH) and gamma-glutamyl transferase (GGT). Risk factors for coagulation dysfunction included extended treatment duration, ICU admission, elevated baseline creatinine (Cr), sepsis, and septic shock. Notably, co-administration of meloxicillin and higher baseline red blood cell (RBC) levels appeared to be protective.
Conclusion:
This study constructed an online dynamic nomogram with good discrimination and calibration, which can help to identify high-risk patients and assist clinicians in early risk stratification and individualized treatment planning.
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