CLINICAL CHARACTERISTICS AND OUTCOMES IN ADULTS WITH BACTERIAL MENINGITIS AND NEGATIVE CEREBROSPINAL FLUID CULTURES
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Updated: Nov 1, 2026

Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid for the Detection of Central Nervous System Pathogens
Published on: April 17, 2026
Evelien H G M Drost1, Tess van Stegeren1, Eva N Schepers1
1Amsterdam UMC, location University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam, the Netherlands.
Objectives:
Ten to thirty percent of patients with bacterial meningitis have negative CSF cultures, yet their clinical characteristics and outcome remain poorly defined.
Methods:
Between 2006 and 2023, adults with bacterial meningitis were prospectively included in a nationwide cohort study. Patients with negative CSF cultures were compared to those with positive CSF cultures. Outcome was assessed using the Glasgow Outcome Scale, with scores of 1-4 classified as unfavourable. CSF samples from microbiology-negative patients underwent additional testing with the IS-pro assay, a broad-spectrum PCR technique.
Results:
CSF cultures were negative in 413 of 3,132 episodes (13%). A pathogen was identified in 328 (80%) through blood culture, CSF bacterial PCR, or antigen testing, leaving 85 episodes without microbiological confirmation. Patients with negative CSF cultures more often received pre-admission antibiotics (13% vs 10%, p=0.02) and had lower rates of unfavourable outcome (29% vs 39%, p<0.001). Blood cultures were positive in 53%, and CSF PCR detected a pathogen in 49%. The IS-pro assay detected Streptococcus pneumoniae (n=5), Streptococcus bovis group/Streptococcus intermedius (n=5), and Streptococcus constellatus (n=1).
Conclusions:
Bacterial meningitis patients with negative CSF cultures have more favourable outcomes. Combining CSF cultures with blood cultures and CSF PCR improves pathogen detection, while broad-spectrum PCR may help identify atypical pathogens.
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