Bacterial Load in Cerebrospinal Fluid Predicts Unfavourable Outcome in Pneumococcal Meningitis: A Prospective Nationwide Cohort Study

Objectives: The objective of this study was to determine the role of cerebrospinal fluid (CSF) bacterial load in adults with pneumococcal meningitis. Methods: We quantified bacterial load in CSF samples from the diagnostic lumbar puncture of adults with community-acquired pneumococcal meningitis. We also measured CSF concentrations of complement component 5a (C5a), and determined associations between bacterial load, clinical characteristics, C5a and unfavourable outcome (Glasgow Outcome Scale score <5). Results: Bacterial load was quantified in 152 CSF samples. Median age of these patients was 61 years (interquartile range [IQR] 51–68), and 69 of 152 (45%) were female. Median CSF bacterial load was 1.6 × 10⁴ DNA copies/mL (IQR 3.4 × 10³–1.2 × 10⁵), and did not correlate with CSF white cell count nor with CSF protein concentrations. Median CSF C5a concentration was 35.8 mg/L (IQR 15.9–105.6), and was moderately correlated with CSF bacterial loads (Spearman's rho = 0.42; p < 0001). High bacterial loads were associated with development of complications, such as circulatory shock (OR per logarithmic increase: 2.4, 95% CI: 2.0–2.9; p < 0.001) and cerebrovascular complications [OR: 1.9, 95% CI: 1.6–2.3; p < 0.001]). High bacterial loads were also associated with unfavourable outcome (OR: 2.8, 95% CI: 2.4–3.3; p < 0.001) and death (OR: 3.1, 95% CI: 2.6–3.8; p < 0.001). In a multivariable regression model including age, immunocompromised state, extrameningeal infection focus, admission Glasgow Coma Scale score and CSF C5a concentration, CSF bacterial load remained an independent predictor of unfavourable outcome (adjusted OR: 2.5, 95% CI: 1.6–3.9; p < 0.001). Discussion: High CSF bacterial load predicts the development of complications and unfavourable outcome in adults with pneumococcal meningitis.