Community-acquired bacterial meningitis in adults in Denmark (2015–2023): a prospective, nationwide, population-based cohort study

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Background Data on clinical presentation and care pathways of community-acquired bacterial meningitis (CABM) remain scarce, especially in relation to whether and how pathogens are detected. This study aimed to examine clinical phenotypes of CABM. Methods Nationwide, prospective, population-based cohort study of all adults diagnosed with CABM in Denmark from 2015 to 2023. Patients were hierarchically categorised as: 1) Positive cerebrospinal fluid (CSF) cultures, 2) Positive CSF polymerase chain reaction (PCR) tests or microscopy, 3) Positive blood cultures and CSF pleocytosis, 4) Other microbiological tests and CSF pleocytosis, and 5) Unknown pathogen and CSF pleocytosis. Findings Among 1192 CABM episodes in 1174 adults (median age 65 years [interquartile range 52–75]; 597/1192 [50%] females), main pathogens were S. pneumoniae 437/1192 (37%), S. aureus 97/1192 (8%), and β-haemolytic streptococci 87/1192 (7%). Neisseria meningitidis caused 63/1192 (5%) episodes and 233/1192 (20%) had unknown aetiology. CSF culture-positive cases (575/1174; 48%) and PCR-positive cases (202/1174; 17%) were characterised by neck stiffness, altered mental status, high inflammatory markers, pneumococcal aetiology, and early treatment. Cases diagnosed by blood cultures and CSF pleocytosis (162/1174; 14%) were mainly due to S. aureus or β-haemolytic streptococci and were characterized by headache, altered mental status, lower CSF leukocyte counts, and late treatment. Cases diagnosed by other microbiological tests (20/1174; 2%) were often younger individuals with otogenic meningitis. Thirty-day mortality was 149/1192 (13%), ranging from 10/233 (4%) in unknown aetiology to 36/162 (22%) if diagnosed by positive blood cultures and CSF pleocytosis. One-year mortality was 221/1192 (19%). Independent prognostic factors of mortality were age, immunocompromise, altered mental status, bacteraemia, and S. aureus and β-haemolytic streptococci aetiologies. Interpretation Distinct clinical phenotypes were associated with differences in pathogen distributions, timely diagnosis, treatment, and outcome. This knowledge is crucial for improvements in healthcare pathways and analyses of guideline adherence. Funding Jacob Bodilsen was supported by the Danish Independent Research Foundation (10.46540/5243-00013B).

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