Background: The discrimination of bacterial meningitis (BM) versus viral meningitis (VM) shapes up as a problem, when laboratory data are not equivocal, in particular, when Gram stain is negative.

Methodology/principal findings: With the aim to determine reliable marker for bacterial or viral meningitis, we subjected cerebrospinal fluid (CSF) to a quantitative proteomic screening. By using a recently established 2D-DIGE protocol which was adapted to the individual CSF flow, we compared a small set of patients with proven BM and VM. Thereby, we identified six potential biomarkers out of which Prostaglandin-H2 D-isomerase was already described in BM, showing proof of concept. In the subsequent validation phase on a more comprehensive collective of 80 patients, we could validate that in BM high levels of glial fibrillary acidic protein (GFAP) and low levels of soluble amyloid precursor protein alpha/beta (sAPPalpha/beta) are present as possible binding partner of Fibulin-1.

Conclusions/significance: We conclude that our CSF flow-adapted 2D-DIGE protocol is valid especially in comparing samples with high differences in total protein and suppose that GFAP and sAPPalpha/beta have a high potential as additional diagnostic markers for differentiation of BM from VM. In the clinical setting, this might lead to an improved early diagnosis and to an individual therapy.