Document Detail


New understandings on the pathophysiology of bacterial meningitis.
MedLine Citation:
PMID:  20216309     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE OF REVIEW: 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.
RECENT FINDINGS: 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.
SUMMARY: 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.
Authors:
Uwe Koedel; Matthias Klein; Hans-Walter Pfister
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current opinion in infectious diseases     Volume:  23     ISSN:  1473-6527     ISO Abbreviation:  Curr. Opin. Infect. Dis.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-04-21     Completed Date:  2010-07-12     Revised Date:  2012-01-31    
Medline Journal Info:
Nlm Unique ID:  8809878     Medline TA:  Curr Opin Infect Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  217-23     Citation Subset:  IM    
Affiliation:
Department of Neurology, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany. Uwe.Koedel@med.uni-muenchen.de
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MeSH Terms
Descriptor/Qualifier:
Anti-Bacterial Agents / therapeutic use
Humans
Inflammation / immunology,  pathology
Meningitis, Bacterial / drug therapy,  immunology,  pathology*,  physiopathology*
Neutrophils / immunology
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents

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