The predominant organisms vary based on the age and underlying condition of the host. Historically, bacterial meningitis in the United States has been primarily caused by five organisms: Streptococcus pneumoniae, Neisseria meningitidis, Listeria monocytogenes, Haemophilus influenzae, and group B streptococcus. However, immunization of young children against H. influenzae and S. pneumoniae has had a marked impact on meningitis in the United States, raising the average age of meningitis due to these five pathogens from 15 months old to 25 years old [8].

S. pneumoniae accounts for almost half of the cases of community-acquired bacterial meningitis in the United States in all age groups beyond the neonatal period [8]. It is associated with a sixfold higher risk of unfavorable outcome (death, neurologic sequelae) than other pathogens [9]. Pneumococcal meningitis is more common in the setting of a CSF leak, hypogammaglobulinemia, asplenia, alcoholism, head trauma, or cochlear implant [10,11]. Routine infant immunization against S. pneumoniae has also reduced the incidence of pneumococcal meningitis in older children and adults due to a reduction in S. pneumoniae carriage in the younger population [12,13]. N. meningitidis accounts for approximately one fourth of cases of meningitis in the United States [8]. Nasal carriage of N. meningitidis gradually increases from infancy and peaks in the teenage years [14]; it is the most common cause of meningitis in older children and young adults. It is the one form of bacterial meningitis associated with epidemic spread. A polysaccharide-protein conjugate vaccine is available in the United States but does not provide protection against serogroup B strains. The vaccine is currently recommended for preadolescents, freshman entering college, and military recruits [15]. L. monocytogenes is a common cause of meningitis in the neonatal period or in the setting of malignancy, immunosuppression, or alcoholism. Approximately 30% of patients have no apparent immunocompromising condition; most of these individuals are older than 50 years [8,16,17]. H. influenzae type B was formerly the most common cause of bacterial meningitis in young children. Vaccination of children has reduced the incidence of invasive H. influenzae type B
disease by more than 80% [8,18]. Sporadic cases have recently been reported in unimmunized and partially immunized children, however [19]. H. influenzae in adults is uncommon and is usually associated with predisposing factors, such as anatomic defects (head trauma, CSF leaks) or defects in humoral immunity [20].

Gram-negative bacillary meningitis occurs in the neonatal period or after neurosurgery or trauma [21]. Community-acquired Gram-negative bacillary meningitis is rare in adults [21]. When it occurs, it is usually a complication of bacteremia from a distant site, often the urinary tract.

Staphylococcus aureus meningitis is associated with neurosurgery or trauma. Community-acquired cases occur in the presence of a focus of infection outside the CNS, such as endocarditis or soft tissue infections, and have a worse prognosis [22]. Meningitis in patients with CSF shunts is most commonly caused by skin flora (S. aureus, Staphylococcus epidermidis, Propionibacterium acnes) and Gram-negative bacilli [23]. These infections can have an indolent presentation and milder CSF abnormalities [3,23]. Use of shunt catheters impregnated with antibiotics has shown some promise in reducing the incidence of infection [24].

Several additional species of streptococci can cause meningitis. Group B streptococcus, Streptococcus agalactiae, is the most common cause of neonatal meningitis [8]. Rates of group B streptococcal invasive disease in adults are increasing, particularly in diabetic patients, but only a small proportion present as meningitis [25]. Streptococcus suis is an increasingly common cause of meningitis in Asia and should be considered in travelers, particularly those who may have ingested raw pork or had contact with pigs [26,27]. LP associated with the use of catheters for anesthesia and imaging procedures has been associated with the introduction of α-hemolytic streptococci in rare cases [28]. Anaerobic bacteria and other streptococci are otherwise uncommon causes of meningitis that are usually related to spread from brain abscess or parameningeal foci [29].

Bacterial seeding of the meninges usually arises from hematogenous spread. Spread from contiguous foci of infection is more often a cause of intracranial abscess. Bacteremia can arise from simple colonization of the nasopharynx, though colonization alone is obviously not sufficient, since 10% of the population is colonized with N. meningitidis at any given time [30]. The bacterial species most commonly associated with meningitis bind the laminin receptor on microvascular endothelial cells, potentially facilitating entry to the CNS [31]. Most meningitis pathogens also secrete immunoglobulin A proteases, facilitating immune evasion at mucosal sites [14]. Inadequate levels of antibody specific for the invading organism (such as occurs at the extremes of age or in acquired immunodeficiencies) and opsonophagocytic deficiencies (such as in asplenia, diabetes, or alcoholism) are the most commonly recognized risk factors for meningitis [32]. Individuals with terminal complement component deficiencies may experience recurrent episodes of meningococcal meningitis, though with lower mortality rates [33].

Once bacteria reach the CSF, both bacterial and host factors contribute to disease. Recognition of bacterial components, including cell wall molecules and bacterial DNA, leads to elaboration of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin-1, and interleukin-6 by leukocytes and endothelial cells. One of the major consequences is the disruption of the tight junctions of the blood–brain barrier. Additional inflammation, caused in part by increased migration and activation of neutrophils, triggers release of tissue factor (which aids thrombus formation and disrupts cerebral perfusion), nitric oxide (which disrupts autoregulation of blood flow and can have direct toxic effects on neurons), and matrix metalloproteinases (which can also disrupt endothelial junctions and impair neuronal function). Neuronal damage is further worsened by resulting increases in intracranial pressure [34,35].

Antibiotics that rapidly lyse bacteria generate a transient increase in inflammation as a response to the release of bacterial cell wall components [36]. Adjunctive steroid therapy acts to decrease inflammation associated with bacterial lysis [37]. The body also deploys endogenous immunomodulators such as TNF-related apoptosis-inducing ligand (TRAIL), which has been shown to reduce neuronal damage in animal models [38].

The clinical consequence of these pathologic processes is a generalized disturbance of cerebral function. An early phase of agitation or mania may be noted. Lethargy progresses to obtundation and sometimes coma. Seizures occur early in 20% to 30% of adults with meningitis [21]. Hyponatremia, caused by the syndrome of inappropriate antidiuretic hormone (SIADH) secretion, may contribute to obtundation and seizures. Focal neurologic deficits may be observed; sensorineural deafness is particularly common. Neurologic impairment persists in approximately 30% of survivors of meningitis in adulthood [6].

The appropriate management of patients with bacterial meningitis involves prompt initiation of antimicrobial and anti-inflammatory therapy, aggressive control of the potential complications, and prevention of spread of disease [3]. Overall mortality from bacterial meningitis is in the range of 20% to 30% [9,21,69]. However, mortality rates are significantly influenced by both the pathogen, with S. pneumoniae among the most deadly, and the host, with elderly patients among the most
susceptible [9,21]. Consequently, most patients should be treated in an intensive care setting.