Pathogenesis and pathophysiology of bacterial meningitis.

Despite the availability of bactericidal antibiotics with potent in vitro activity against the major meningeal pathogens, the morbidity and mortality from bacterial meningitis remains unacceptably high. Animal models have proven to be extremely valuable in the study of the pathogenesis and pathophysiology of bacterial meningitis, with the hopes of providing new information that may lead to an improved outcome from this disorder. Bacterial meningitis usually begins with nasopharyngeal colonization by a new organism, followed by invasion and bacteremia. Subsequently there is central nervous system invasion, although the exact site and mechanism of meningeal invasion are unknown. The generation of an intense subarachnoid space inflammatory response, induced by release of bacterial virulence factors and/or inflammatory cytokines, contributes to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema, increased intracranial pressure, and alterations of cerebral blood flow. Attenuation of this inflammatory response (e.g. by co-administration of antiinflammatory agents) may diminish many of these pathophysiologic consequences of meningitis, and perhaps improve morbidity and mortality from this disorder.