New understandings on the pathophysiology of bacterial meningitis.
OBJECTIVE
Currently, dexamethasone is the only adjuvant of proven benefit in bacterial meningitis. Dexamethasone halves the risk of poor outcome, but only in selected patient groups. New therapies based upon an understanding of the pathophysiology are needed. This article summarizes our knowledge on the pathophysiology of bacterial meningitis with special emphasis on pneumococcal meningitis, the experimentally best characterized subtype.


RESULTS
Experimental studies made clear that the harmful inflammatory reaction is initiated by the interaction of bacterial products with host pattern recognition receptors (PRRs) such as Toll-like receptors. PRR signalling leads to MyD88-dependent production of proinflammatory cytokines of the interleukin-1 family. Secretion of interleukin-1 family cytokines forms a positive feedback loop that boosts MyD88-dependent production of proinflammatory mediators. As a consequence, great numbers of neutrophils are recruited to the subarachnoid space. Activated neutrophils release many potentially cytotoxic agents including oxidants and matrix metalloproteinases that can cause collateral damage to brain tissue. Additionally to the inflammatory response, direct bacterial cytotoxicity has been identified as a contributor to tissue damage.


CONCLUSIONS
Promising pathophysiologically targeted approaches for adjunctive therapy of acute bacterial meningitis include limiting the release of toxic bacterial products (e.g. nonbacteriolytic antibiotics) and interfering in the generation of host-derived cytotoxins.
Koedel
Uwe
U
Department of Neurology, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany. Uwe.Koedel@med.uni-muenchen.de
Klein
Matthias
M
Pfister
Hans-Walter
HW
D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D016920:Meningitis, Bacterial / Q000188:drug therapy / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D009504:Neutrophils / Q000276:immunology
D000900:Anti-Bacterial Agents