Optimal use of β-lactams in neonates: machine learning-based clinical decision support systemResearch in context
Bo-Hao Tang,
Bu-Fan Yao,
Wei Zhang,
Xin-Fang Zhang,
Shu-Meng Fu,
Guo-Xiang Hao,
Yue Zhou,
De-Qing Sun,
Gang Liu,
John van den Anker,
Yue-E Wu,
Yi Zheng,
Wei Zhao
Affiliations
Bo-Hao Tang
Department of Pharmacy, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
Bu-Fan Yao
Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
Wei Zhang
Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
Xin-Fang Zhang
Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
Shu-Meng Fu
Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
Guo-Xiang Hao
Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
Yue Zhou
Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
De-Qing Sun
Department of Pharmacy, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
Gang Liu
Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Jinan, China
John van den Anker
Division of Clinical Pharmacology, Children’s National Hospital, Washington, DC, USA; Departments of Pediatrics, Pharmacology & Physiology, Genomics & Precision Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA; Department of Pediatric Pharmacology and Pharmacometrics, University of Basel Children’s Hospital, Basel, Switzerland
Yue-E Wu
Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
Yi Zheng
Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
Wei Zhao
Department of Pharmacy, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China; Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China; NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Shandong University, Jinan, China; Corresponding author. Department of Pharmacy, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
Summary: Background: Accurate prediction of the optimal dose for β-lactam antibiotics in neonatal sepsis is challenging. We aimed to evaluate whether a reliable clinical decision support system (CDSS) based on machine learning (ML) can assist clinicians in making optimal dose selections. Methods: Five β-lactam antibiotics (amoxicillin, ceftazidime, cefotaxime, meropenem and latamoxef), commonly used to treat neonatal sepsis, were selected. The CDSS was constructed by incorporating the drug, patient, dosage, pharmacodynamic, and microbiological factors. The CatBoost ML algorithm was used to build the CDSS. Real-world studies were used to evaluate the CDSS performance. Virtual trials were used to compare the CDSS-optimized doses with guideline-recommended doses. Findings: For a specific drug, by entering the patient characteristics and pharmacodynamic (PD) target (50%/70%/100% fraction of time that the free drug concentration is above the minimal inhibitory concentration [fT > MIC]), the CDSS can determine whether the planned dosing regimen will achieve the PD target and suggest an optimal dose. The prediction accuracy of all five drugs was >80.0% in the real-world validation. Compared with the PopPK model, the overall accuracy, precision, recall, and F1-Score improved by 10.7%, 22.1%, 64.2%, and 43.1%, respectively. Using the CDSS-optimized doses, the average probability of target concentration attainment increased by 58.2% compared to the guideline-recommended doses. Interpretation: An ML-based CDSS was successfully constructed to assist clinicians in selecting optimal β-lactam antibiotic doses. Funding: This work was supported by the National Natural Science Foundation of China; Distinguished Young and Middle-aged Scholar of Shandong University; National Key Research and Development Program of China.
