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Pathophysiology of bacterial meningitis

Open ArchivePublished:March 08, 2010DOI:https://doi.org/10.1016/j.ijid.2010.02.2228
      Bacterial meningitis is characterized by the entry of bacteria into the cerebrospinal fluid (CSF) and bacterial growth in this compartment leading to inflammation within the CSF and the adjacent brain tissue. Long-term neurological sequelae and death are caused jointly by the following factors: (1) The systemic inflammatory response of the host leads to leukocyte extravasation into the subarachnoid space, an increased CSF outflow resistance, and brain edema. The resulting elevated intracranial pressure is an important cause of death in the acute phase and of long-term sequelae. Systemic inflammation can also cause vasculitis, cerebral venous thrombosis and secondary ischemia. (2) Immune cells within the brain parenchyma, in particular microglia, can be stimulated by proinflammatory bacterial compounds, which can directly lead to neuronal injury. (3) Some bacterial compounds, e.g., pneumolysin, possess direct toxicity on neurons. Neuronal injury is mediated by the release of reactive oxygen intermediates, proteases, cytokines and excitatory amino acids, the activation of transcription factors, caspases, matrix metalloproteases and other proteases.
      Rapid initiation of effective antibiotic therapy sterilizes the CSF and reduces mortality of bacterial meningitis. In industrialized countries, dexamethasone as an adjunctive therapy to antibiotic treatment, improves outcome of bacterial meningitis, particularly of Streptococcus pneumoniae meningitis. In experimental meningitis, dexamethasone as an adjunct to antibiotic treatment causes an increase of neuronal injury in the dentate gyrus of the hippocampal formation, suggesting that corticosteroids might not be the ideal adjunctive therapy. Several approaches that interfere selectively with the mechanisms of neuronal injury, including the use of non-bacteriolytic bactericidal protein synthesis-inhibiting antibiotics, antioxidants and inhibitors of transcription factors, matrix metalloproteinases, and caspases, are effective in animal models. However, adequate clinical studies are lacking. A recent randomized clinical study points to a beneficial effect of adjunctive oral glycerol.

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