Association of Staphylococcus aureus bloodstream infection with 7-day incident delirium in critically Ill adults: a propensity-weighted competing risk analysis.

BACKGROUND: Delirium is a frequent manifestation of acute brain dysfunction in critically ill patients with bloodstream infections (BSI). While the association between sepsis and delirium is well-established, pathogen-specific neurotoxic effects, particularly those induced by Staphylococcus aureus (S. aureus), remain inadequately elucidated. This study aimed to evaluate the independent association between S. aureus BSI and the risk of 7-day incident delirium in critically ill adults.

METHODS: A retrospective cohort study was conducted using the MIMIC-IV database, including 3,226 adult patients with confirmed BSI. To minimize confounding bias, a "doubly robust" estimation approach was employed, combining Inverse Probability of Treatment Weighting based on Covariate Balancing Propensity Scores (IPTW-CBPS) with multivariable adjustment. Fine-Gray proportional subdistribution hazard models were utilized to assess the association between pathogen status and 7-day delirium, accounting for death as a competing risk. Explainable machine learning using the eXtreme Gradient Boosting (XGBoost) algorithm and Shapley Additive exPlanations (SHAP) value analysis was performed to identify feature importance. Sensitivity analyses for the 3-day acute risk and methicillin-resistant Staphylococcus aureus (MRSA) phenotype were also conducted.

RESULTS: Among 3,226 patients, 618 (19.2%) were identified with S. aureus BSI. In the fully adjusted Fine-Gray model, compared with Gram-negative infections, S. aureus BSI was robustly and independently associated with an increased risk of 7-day incident delirium (sHR 1.39; 95% CI 1.11-1.74; p = 0.005). This association was even more pronounced within the 3-day acute window (sHR 1.60; 95% CI 1.27-2.02; p < 0.001). Conversely, compared with Gram-negative BSI, the MRSA phenotype showed no significant independent association with delirium risk (sHR 1.12; 95% CI 0.81-1.55; p = 0.488). SHAP analysis identified S. aureus infection as the fourth most influential feature for delirium, surpassing age and sedative exposure. Subgroup analyses revealed that the pathogen-specific impact was significantly more prominent in patients with lower baseline illness severity (SOFA < 5) and those without a history of dementia (P for interaction < 0.001 and 0.004, respectively). SHAP value analysis further confirmed this finding by demonstrating a higher risk contribution of S. aureus in patients with lower SOFA scores.

CONCLUSIONS: S. aureus BSI is a robust independent risk factor for 7-day incident delirium compared with Gram-negative BSI, with the hazard being more pronounced within the first 3 days of infection. Notably, compared with Gram-negative BSI, the MRSA phenotype was not independently associated with delirium risk. Identifying S. aureus as a critical driver of early brain dysfunction provides a pathogen-specific framework for risk stratification. Consequently, clinicians should prioritize early neurocognitive monitoring and targeted neuroprotection (e.g. the ABCDEF bundle) for all patients with S. aureus infection.