A Multi-Phase Analysis of Blood Culture Stewardship: Machine Learning Prediction, Expert Recommendation Assessment, and LLM Automation

Blood cultures are often over ordered without clear justification, straining healthcare resources and contributing to inappropriate antibiotic use pressures worsened by the global shortage. In study of 135483 emergency department (ED) blood culture orders, we developed machine learning (ML) models to predict the risk of bacteremia using structured electronic health record (EHR) data and provider notes via a large language model (LLM). The structured models AUC improved from 0.76 to 0.79 with note embeddings and reached 0.81 with added diagnosis codes. Compared to an expert recommendation framework applied by human reviewers and an LLM-based pipeline, our ML approach offered higher specificity without compromising sensitivity. The recommendation framework achieved sensitivity 86%, specificity 57%, while the LLM maintained high sensitivity (96%) but over classified negatives, reducing specificity (16%). These findings demonstrate that ML models integrating structured and unstructured data can outperform consensus recommendations, enhancing diagnostic stewardship beyond existing standards of care.