Machine Learning for Pre-Culture ESBL Risk Stratification to Guide Empiric Antibiotic Selection: A 12-Hospital Study of Enterobacteriaceae Cultures
TL;DR
A cost-sensitive XGBoost model predicting an ESBL phenotype at culture ordering at culture ordering was developed, identifying prior ESBL colonization as the dominant predictor, ahead of prior organism burden and neighborhood deprivation; removing deprivation features caused minimal performance loss, enabling equitable bedside deployment.
Abstract
Empiric antibiotic therapy for suspected ESBL-producing Enterobacteriaceae must be selected 48-72 hours before culture results, forcing clinicians to choose between undertreating resistant infections and overusing carbapenems that drive further resistance. We developed a cost-sensitive XGBoost model predicting an ESBL phenotype (resistance to ceftriaxone, ceftazidime, cefepime or piperacillin-tazobactam) at culture ordering using 45 pre-culture EHR features across 132,955 cultures from 72,217 patients at 12 hospitals (14.41% with the ESBL phenotype). Cultures were partitioned at the patient level. At 90% sensitivity, the model achieved 95.8% NPV, reducing post-test ESBL probability to 4.2%, a threshold that may support safe carbapenem-sparing in non-ICU settings, while sparing 307 of every 1,000 cultures an unnecessary broad-spectrum course at the cost of 14 missed ESBL cases per 1,000. SHAP analysis identified prior ESBL colonization as the dominant predictor, ahead of prior organism burden and neighborhood deprivation; removing deprivation features caused minimal performance loss ($\Delta\text{AUROC} = -0.020$), enabling equitable bedside deployment. Discrimination was unchanged under a strict IDSA ESBL-E definition (AUROC 0.766), with specimen type added as a predictor (0.764) and without any class-imbalance correction (0.762), and ranged from 0.71 to 0.78 across organism strata.