Prediction of vancomycin-resistant phenotype in ICU-onset sterile-site Enterococcus-positive cultures: development and pseudo-temporal validation of a clinical prediction model using MIMIC-IV

Background Vancomycin-resistant enterococci challenge intensive care. During the interval between organism identification and final phenotypic antimicrobial susceptibility testing, clinicians must balance delayed effective anti-VRE therapy against unnecessary anti-VRE exposure. We aimed to develop and pseudo-temporally validate a model for the vancomycin-resistance phenotype of the index isolate; the model does not determine whether the isolate represents clinically significant infection. Methods In this retrospective MIMIC-IV cohort, adult ICU admissions with a sterile-site Enterococcus -positive culture obtained more than 48 hours after ICU admission were assigned by de-identified anchor-year group to development (groups labelled 2008–2016; n = 552) or pseudo-temporal validation (2017–2022; n = 259). Predictors were restricted to information available by specimen collection. Elastic Net with bootstrap stability screening retained 19 of 141 candidates; four tree-based models were comparators. Results Among 811 admissions (507 resistant isolates; prevalence, 62.5%), Elastic Net achieved a validation AUROC of 0.835 (95% CI, 0.778–0.889) and calibration slope of 0.91 (0.71–1.18). Tree-model AUROCs were 0.842–0.855; non-significant pairwise DeLong tests were evidence insufficient to detect differences, not evidence of equivalence. Removing both species indicators reduced AUROC to 0.657 (DeLong P < 0.001). Development-OOF-fitted Platt scaling improved validation slopes for Random Forest, XGBoost, and CatBoost from 1.41, 2.41, and 1.46 to 0.94, 1.02, and 1.01. At the Youden index threshold, Elastic Net sensitivity was 0.884 and specificity was 0.690. In exploratory decision-curve analysis, its net benefit did not exceed treat-all at thresholds 0.10 or 0.20; the paired difference was 0.044 (95% CI, 0.014–0.071) at 0.30. Conclusions The model predicts isolate resistance phenotype, not adjudicated infection, and is not a stand-alone treatment rule. These estimates are specific to a single-center cohort with high VRE prevalence. Independent external validation, local recalibration, clinical adjudication, and periodic updating are prerequisites for use.