Machine learning models for coagulation dysfunction risk in inpatients administered β-lactam antibiotics

Front Pharmacol. 2024 Nov 26:15:1503713. doi: 10.3389/fphar.2024.1503713. eCollection 2024.

Abstract

The β-Lactam antibiotics represent a widely used class of antibiotics, yet the latent and often overlooked risk of coagulation dysfunction associated with their use underscores the need for proactive assessment. Machine learning methodologies can offer valuable insights into evaluating the risk of coagulation dysfunction associated with β-lactam antibiotics. This study aims to identify the risk factors associated with coagulation dysfunction related to β-lactam antibiotics and to develop machine learning models for estimating the risk of coagulation dysfunction with real-world data. A retrospective study was performed using machine learning modeling analysis on electronic health record data, employing five distinct machine learning methods. The study focused on adult inpatients discharged from 1 January 2018, to 31 December 2021, at the First Affiliated Hospital of Shandong First Medical University. The models were developed for estimating the risk of coagulation dysfunction associated with various β-lactam antibiotics based on electronic health record feasibility. The dataset was divided into training and test sets to assess model performance using metrics such as total accuracy and area under the curve. The study encompassed risk-factor analysis and machine learning model development for coagulation dysfunction in inpatients administered different β-lactam antibiotics. A total of 45,179 participants were included in the study. The incidence of coagulation disorders related to cefazolin sodium, cefoperazone/sulbactam sodium, cefminol sodium, amoxicillin/sulbactam sodium, and piperacillin/tazobactam sodium was 2.4%, 5.4%, 1.5%, 5.5%, and 4.8%, respectively. Machine learning models for estimating coagulation dysfunction associated with each β-lactam antibiotic underwent validation with 5-fold cross-validation and test sets. On the test set, the optimal models for cefazolin sodium, cefoperazone/sulbactam sodium, cefminol sodium, amoxicillin/sulbactam sodium, and piperacillin/tazobactam sodium yielded AUC values of 0.798, 0.768, 0.919, 0.783, and 0.867, respectively. The study findings suggest that machine learning classifiers can serve as valuable tools for identifying patients at risk of coagulation dysfunction associated with β-lactam antibiotics and intervening based on high-risk predictions. Enhanced access to administrative and clinical data could further enhance the predictive performance of machine learning models, thereby expanding pharmacovigilance efforts.

Keywords: coagulation disorders; machine learning; pharmacovigilance; risk factors; β-lactam antibiotics.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Research project of disease treatment and rational use of drugs of Shandong Pharmaceutical Association (DRM2022007), Shandong Pharmaceutical Association Hospital Pharmacy Special Scientifc Research Project (yyyx2021zd-03), Shandong Pharmaceutical Association Hospital Rational Drug Use Young and Middle-aged Scientific Research (hlyy-2024-01), Shandong Pharmaceutical Association Medical Institution Pharmacovigilance Young and Middle-aged Project (ywjj-2024-01), Shanghai sailing program (22YF1440300), and Shanghai Jiaotong University “Jiaotong University Star” program (medical-engineering cross-research, YG2022QN015).