Community-Acquired Bacterial Meningitis: Risk Stratification for Adverse Clinical Outcome and Effect of Antibiotic Timing

Abstract

BACKGROUND: Community-acquired bacterial meningitis causes substantial morbidity and mortality in adults. OBJECTIVE: To create and test a prognostic model for persons with community-acquired bacterial meningitis and to determine whether antibiotic timing influences clinical outcome. DESIGN: Retrospective cohort study; patients were divided into derivation and validation samples. SETTING: Four hospitals in Connecticut. PATIENTS: 269 persons who, between 1970 and 1995, had community-acquired bacterial meningitis microbiologically proven by a lumbar puncture done within 24 hours of presentation in the emergency department. MEASUREMENTS: Baseline clinical and laboratory features and times of arrival in the emergency department, performance of lumbar puncture, and administration of antibiotics. The target end point was the development of an adverse clinical outcome (death or neurologic deficit at discharge). RESULTS: For the total group, the hospital mortality rate was 27%. Fifty-six of 269 patients (21 %) developed a neurologic deficit, and in 9% the neurologic deficit persisted at discharge. Three baseline clinical features (hypotension, altered mental status, and seizures) were independently associated with adverse clinical outcome and were used to create a prognostic model from the derivation sample. The prediction accuracy of the model was determined by using the concordance index (c-index). For both the derivation sample (c-index, 0.73 [95% CI, 0.65 to 0.81]) and the validation sample (c-index, 0.81 [CI, 0.71 to 0.92]), the model predicted adverse clinical outcome significantly better than chance. For the total group, the model stratified patients into three prognostic stages: low risk for adverse clinical outcome (9%; stage I), intermediate risk (33%; stage II), and high risk (56%; stage III) (P=0.001). Adverse clinical outcome was more common for patients in whom the prognostic stage advanced from low risk (P=0.008) or intermediate risk (P=0.003) at arrival in the emergency department to high risk before administration of antibiotics. CONCLUSIONS: In persons with community-acquired bacterial meningitis, three baseline clinical features of disease severity predicted adverse clinical outcome and stratified patients into three stages of prognostic severity. Delay in therapy after arrival in the emergency department was associated with adverse clinical outcome when the patient's condition advanced to the highest stage of prognostic severity before the initial antibiotic dose was given.