Clinical features, etiologies, and outcomes in adult patients with meningoencephalitis requiring intensive care (EURECA): an international prospective multicenter cohort study

Purpose: We aimed to characterize the outcomes of patients with severe meningoencephalitis requiring intensive care. Methods: We conducted a prospective multicenter international cohort study (2017–2020) in 68 centers across 7 countries. Eligible patients were adults admitted to the intensive care unit (ICU) with meningoencephalitis, defined by an acute onset of encephalopathy (Glasgow coma scale (GCS) score ≤ 13), a cerebrospinal fluid pleocytosis ≥ 5 cells/mm3, and at least two of the following criteria: fever, seizures, focal neurological deficit, abnormal neuroimaging, and/or electroencephalogram. The primary endpoint was poor functional outcome at 3 months, defined by a score of three to six on the modified Rankin scale. Multivariable analyses stratified on centers investigated ICU admission variables associated with the primary endpoint. Results: Among 599 patients enrolled, 589 (98.3%) completed the 3-month follow-up and were included. Overall, 591 etiologies were identified in those patients which were categorized into five groups: acute bacterial meningitis (n = 247, 41.9%); infectious encephalitis of viral, subacute bacterial, or fungal/parasitic origin (n = 140, 23.7%); autoimmune encephalitis (n = 38, 6.4%); neoplastic/toxic encephalitis (n = 11, 1.9%); and encephalitis of unknown origin (n = 155, 26.2%). Overall, 298 patients (50.5%, 95% CI 46.6–54.6%) had a poor functional outcome, including 152 deaths (25.8%). Variables independently associated with a poor functional outcome were age > 60 years (OR 1.75, 95% CI 1.22–2.51), immunodepression (OR 1.98, 95% CI 1.27–3.08), time between hospital and ICU admission > 1 day (OR 2.02, 95% CI 1.44–2.99), a motor component on the GCS ≤ 3 (OR 2.23, 95% CI 1.49–3.45), hemiparesis/hemiplegia (OR 2.48, 95% CI 1.47–4.18), respiratory failure (OR 1.76, 95% CI 1.05–2.94), and cardiovascular failure (OR 1.72, 95% CI 1.07–2.75). In contrast, administration of a third-generation cephalosporin (OR 0.54, 95% CI 0.37–0.78) and acyclovir (OR 0.55, 95% CI 0.38–0.80) on ICU admission were protective. Conclusion: Meningoencephalitis is a severe neurologic syndrome associated with high mortality and disability rates at 3 months. Actionable factors for which improvement could be made include time from hospital to ICU admission, early antimicrobial therapy, and detection of respiratory and cardiovascular complications at admission.