Novel Biomarkers for Bacterial Meningitis and Other Central Nervous System Infections

Timely and accurate diagnosis of central nervous system (CNS) infections remains challenging because of nonspecific clinical characteristics and limited diagnostic accuracy of conventional tests. Novel cerebrospinal fluid (CSF) biomarkers may improve early diagnosis and facilitate differentiation between infectious aetiologies. This review summarizes established and emerging CSF biomarkers for the diagnosis of CNS infections, with a focus on bacterial meningitis, and discusses their potential clinical application. Several novel CSF biomarkers have demonstrated excellent diagnostic performance for bacterial meningitis. Among these, CSF C-reactive protein (CRP) has recently been implemented in clinical practice, while heparin-binding protein and combinations of CSF CRP with inflammatory cytokines such as IL-6 and IL-1β show similarly high diagnostic accuracy. Pathogen-specific biomarkers, including CXCL13 for neuroborreliosis and β-D-glucan and galactomannan for fungal CNS infections, further expand the diagnostic repertoire. In addition, multi-omics approaches, including metabolomics, lipidomics, and proteomics, have identified promising candidates such as pyruvate and phosphatidylcholines, although these require further validation. Untargeted techniques, including metagenomic next-generation sequencing and phage immunoprecipitation sequencing, further enhance pathogen detection and may complement microbiological testing. Novel biomarkers have the potential to substantially improve the diagnosis of CNS infections. Several biomarkers for bacterial meningitis are already available for clinical implementation, particularly in patients with intermediate CSF leukocyte counts, where diagnostic uncertainty is greatest. For viral and other CNS infections biomarkers remain scarce. Future studies should focus on validation of emerging biomarkers and on integrating biomarker panels with advanced molecular diagnostic techniques to enable rapid, accurate and clinically applicable diagnostic strategies.