Optimising antibiotic switching via forecasting of patient physiology

Antimicrobial stewardship (AMS) is critical in pediatric intensive care units (PICUs), where diagnostic uncertainty often drives broad-spectrum antibiotic use, increasing antimicrobial resistance and potential long-term harms. Machine learning offers a promising approach for identifying patient-level opportunities for stewardship interventions from electronic health record data, yet prior work has focused largely on adult populations and static tabular representations. We present a systematic benchmarking study of AMS intervention prediction in the PICU across the public Paediatric Intensive Care database a private cohort from the University Children's Hospital Zurich, Switzerland. We define four clinically relevant proxy targets for reducing antibiotic exposure: intravenous-to-oral switching, de-escalation, discontinuation, and short-course therapy. Under a unified evaluation framework, we compare tabular, sequence-based, and graph-based temporal models at multiple temporal resolutions. We find that predictive performance is driven primarily by target prevalence and dataset characteristics rather than model complexity. Sequence models improve the precision-recall trade-off over tabular approaches at coarse (24-hour) resolution, while finer temporal modeling provides limited additional benefit. However, these gains come at the cost of poorer calibration, with simpler tabular models yielding more reliable probability estimates. Our findings highlight the importance of target design, temporal representation, and calibration in clinical machine learning, and provide practical guidance for developing reliable decision support systems for pediatric AMS.

Clinical prediction models in intensive care degrade as data shift, and regulators such as the FDA ask developers to specify bounded update protocols in advance. Evaluations of such protocols assume that apparent drift reflects clinical practice rather than changes in how the database records care. We test whether update strategies can be evaluated on unaudited ICU data, and whether a parameter-bounded update gives up accuracy or attribution stability relative to full fine-tuning once the data are audited. We audit MIMIC-IV 3.1 (2008-2022) for recording artifacts and define a cleaning protocol. On the cleaned cohort, a label-free classifier two-sample test gates updates across three eras. We compare a bounded update, which retrains only treatment-context and fusion parameters, with full fine-tuning for two model families and two targets under a pre-specified non-inferiority margin of 0.015 AUROC, and measure attribution stability against the source model. In 2020-2022 about half of ICU stays have no input or procedure-event records, and a vasopressor ItemID migration makes the 2017-2019 label rate appear to fall when it actually rises. On the cleaned cohort, the gate detects drift in every era, including in physiology-only features, with no false alarms on null data. Bounded updating is non-inferior or superior in 10 of 12 primary cells, but this depends on the target, the model family and learning-rate tuning, and adaptation gains over never updating are small. At a shared learning rate, bounded updates keep physiological attributions more stable in neural models, clearly for vasopressor and less clearly for intubation; with separately tuned rates, full updates are more stable. Audits should precede update evaluation, and the update boundary should be chosen per target.

Many time-series forecasts depend not only on prior observations but also on actions specified during the forecast period. In intensive care units (ICUs), future vital signs and laboratory values are influenced by treatments such as vasopressors. However, models that predict the full future sequence all at once make little use of these treatments, whereas autoregressive models can accumulate errors. We introduce DRIFT, a hybrid framework in which a direct model produces the primary forecast and a recursive, action-conditioned model contributes constrained corrections. We evaluate DRIFT on 6,046 admissions from MIMIC-IV and 8,345 admissions from eICU-CRD. Averaged across the 8-, 24-, and 48-hour forecast endpoints, DRIFT reduces mean absolute error for mean arterial pressure (MAP) by 0.673% relative to an action-conditioned Temporal Fusion Transformer (TFT-action) on MIMIC-IV and achieves the lowest corresponding error among the compared models on eICU-CRD. Although the overall accuracy improvement is modest, a MIMIC-IV audit restricted to windows in which the supplied treatment sequence was altered showed that DRIFT achieved lower observed-target MAP error than TFT-action at 8 and 24 hours. Treatment-sequence alteration increased DRIFT's MAP error by 0.21-0.26 mmHg more than it increased TFT-action's error, with prediction changes occurring primarily after the supplied paths diverged. In a separate robustness experiment, the MAP advantage persisted under three shared checkpoint-selection rules emphasizing overall endpoint error, MAP error, or both equally.