Bacterial meningitis in the patient at risk: intrinsic risk factors and host defense mechanisms

Bacterial meningitis remains a relatively common disease worldwide (40,000 cases per year in the United States) and the mortality rate has not improved in over 30 years. Certain host factors increase the risk of acquiring meningitis and include: age (increased at extremes of life), male sex, low socioeconomic status (crowding), black race, recent nasopharyngeal carriage of a virulent strain, absence of specific bactericidal antibody, maternal factors at birth (neonatal disease), various immunologic defects (neonates, antibody or terminal complement component deficiency, splenectomy, and immunosuppression including the acquired immune deficiency syndrome), and certain chronic diseases (such as alcoholism, cirrhosis, and diabetes mellitus). Bacterial meningitis represents an infection in an area of impaired host resistance. The blood-brain barrier is a major protective mechanism for the central nervous system against circulating bacteria. However, once bacteria gain entry into the subarachnoid space, host defenses are inadequate. Polymorphonuclear leukocytes are at a disadvantage in the fluid medium of the cerebrospinal fluid and surface phagocytosis is inefficient. In addition, antibody and complement concentrations are low (or absent) in purulent cerebrospinal fluid early in the disease course. Functional opsonic and bactericidal activity is lacking; therefore, efficient phagocytosis of encapsulated meningeal pathogens is limited. The result is huge population densities (often 10(7) to 10(8) cfu per milliliter) of bacteria in cerebrospinal fluid. This finding suggests that bactericidal antibiotics with cerebrospinal fluid concentrations much greater than the minimal bacterial concentration of the pathogen are optimal for therapy of meningitis; this principle has been shown in experimental animal models and supported by therapeutic studies in human subjects.