Pathogenesis and pathophysiology of bacterial meningitis.
Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial therapy. Through the use of experimental animal models of infection, a great deal of information has been gleaned concerning the pathogenic and pathophysiologic mechanisms operable in bacterial meningitis. Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia. Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity. Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown. By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space. There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure. Attenuation of this inflammatory response with adjunctive dexamethasone therapy is associated with reduced concentrations of tumor necrosis factor in the cerebrospinal fluid, with diminished cerebrospinal fluid leukocytosis, and perhaps with improvement of morbidity, as demonstrated in recent clinical trials. Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder.
Tunkel
A R
AR
Department of Internal Medicine (Infectious Diseases), Medical College of Pennsylvania, Philadelphia 19129.
Scheld
W M
WM
D000818:Animals; D016470:Bacteremia; D001812:Blood-Brain Barrier; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D006801:Humans; D007427:Intracranial Pressure; D008070:Lipopolysaccharides / Q000633:toxicity; D016920:Meningitis, Bacterial / Q000188:drug therapy / Q000209:etiology*; D013346:Subarachnoid Space / Q000382:microbiology
D008070:Lipopolysaccharides