Cultryx: Precision Diagnostic Stewardship for Blood Cultures Using Machine Learning

Abstract Background The 2024 blood culture bottle shortage brought diagnostic resource allocation to the forefront, reflecting persistent, foundational challenges with low-value testing and empiric treatment approaches under clinical uncertainty. Objective To determine whether a machine learning approach using electronic medical record data can predict bacteremia more effectively than existing systems and practices to guide diagnostic testing and empiric treatment strategies. Methods In a retrospective cohort of 101,812 adult emergency department encounters (2015-2025), we first established an idealized cognitive baseline by evaluating physician and generative AI (GPT-5) application of the professional society-endorsed Fabre framework on a validation subset. We then trained an XGBoost model (Cultryx) on the full cohort to predict bacteremia, benchmarking its performance against real-world clinical heuristics (SIRS, Shapiro Rule). Results For the idealized baseline, physicians applying the Fabre framework achieved 95.7% sensitivity, but GPT-5 automation failed to replicate this standard (71.6% sensitivity). In real-world benchmarking, Cultryx outperformed all clinical heuristics (AUROC 0.810). SIRS lacked specificity (41.2%), driving diagnostic overuse, while the Shapiro Rule lacked sensitivity (70.2%), missing ~30% of bacteremia cases. In contrast, when calibrated to a strict 95% sensitivity target, Cultryx achieved the highest culture volume deferral rate (26.2%, deferring ~ 15,872 bottles with predicted negative results) while maintaining a 98.9% negative predictive value. Cultryx score , a simplified bedside tool, retained a 20.8% deferral rate. Conclusions Machine learning provides a superior, data-driven alternative to mainstream clinical heuristics for predicting bacteremia. By maximizing culture deferment without compromising pathogen detection, Cultryx can conserve diagnostic resources, reduce unnecessary empiric antibiotic exposure, and systematically elevate patient safety. Summary Cultryx, a machine learning model for blood culture stewardship, outperforms standard clinical heuristics in predicting bacteremia. This approach could reduce culture utilization by over 26% while preserving pathogen detection, conserving diagnostic resources, reducing unnecessary antibiotic exposure, and elevating patient safety.