Clinical characteristics and outcomes in adults with bacterial meningitis and negative cerebrospinal fluid cultures

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 3132 episodes (13%). A pathogen was identified in 328 (79%) 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.