Meningitis due to Staphylococcus aureus accounts for 1-9% of cases of bacterial meningitis and is associated with mortality rates of 14-77%.

It usually is associated with neurosurgical interventions (such as cerebrospinal fluid [CSF] shunts), trauma, or underlying conditions such as malignancy, decubitus ulcers, cellulitis, infected intravascular grafts, chronic alcoholism, diabetes mellitus, osteomyelitis, or perirectal abscess. It is uncommon in immunocompetent individuals in the absence of focal infection (eg, pneumonia, osteomyelitis, endocarditis, parameningeal infection, psoas or epidural abscess, sinusitis, tropical pyomyositis), neurosurgical interventions, or congenital dermal sinus.

Neonates are colonized by S aureus soon after birth; major niches include umbilical stump, perineal area, skin, and gastrointestinal tract. Later in life, major niches include anterior nares, and about 25% of children and adults become carriers. Health professionals; individuals with diabetes receiving insulin injections, hemodialysis, or peritoneal dialysis; patients with dermatologic conditions or HIV infection; intravenous (IV) drug users; and trauma patients have higher carriage rates. Carriers experience more postsurgical infections than noncarriers.

The next step after colonization is penetration through the epithelial or mucosal surface. The mechanisms underlying penetration are not completely understood, but trauma, surgery, immunosuppression, and other infections are predisposing conditions. .

Staphylococci are then ingested and killed by polymorphonuclear cells and monocytes. Failure of these defense mechanisms can lead to recurrent or chronic infection. Inherited or acquired defects of chemotaxis, opsonization, or polymorphonuclear leukocyte function (eg, due to severe bacterial infections, rheumatoid arthritis, decompensated diabetes mellitus) predispose patients to continuation of the infection process.

Foreign body infection leads to an acquired phagocytic defect. After hours or days of contact with the foreign body, S aureus produces a polysaccharide/adhesin substance that causes it to adhere to the foreign body and protects it from the environment. The resident phagocytic population close to the foreign body is not able to kill the invading strain. Anchoring of S aureus to foreign substances also modifies its susceptibility to antimicrobial agents. These factors explain the inability of antibiotics alone to eradicate foreign body infection.

S aureus meningitis has 2 different pathogenic mechanisms, as follows:

In the first form, bacteria are introduced during surgery or by trauma or local spreading (especially coagulase-negative staphylococci) from contiguous infection. Bacteria introduced during surgery cause foreign body infection and subsequent postoperative meningitis. Attachment of S aureus to foreign surfaces involves interaction with proteins of the extracellular matrix: fibrinogen, fibronectin, laminin, thrombospondin, vitronectin, elastin, bone sialoprotein, and collagen. S aureus ligands for these host proteins have been characterized, cloned, and sequenced. Patients with this type of infection have a lower mortality rate than those with hematogenous meningitis, which may be explained by early recognition and less systemic involvement.

In the second group, hematogenous or spontaneous meningitis, S aureus is disseminated systemically. Infection is more often community acquired, and the incidence of positive blood culture results is higher, as is mortality rate. S aureus attachment to endothelial cells during septicemia is complex and involves interaction with fibronectin, fibrinogen, and laminin. After adhesion, phagocytosis by endothelial cells and induction of tissue factor procoagulant activity occur. Any localized S aureus infection can lead to bacteremia. In the pre-antibiotic era, mortality rate was 82%. Recent studies reported mortality rates between 30% and 40% in non–drug-using patients with S aureus septicemia.

Patients with S aureus bacteremia can be divided into 2 groups. The first comprises elderly patients with a recognizable primary site of infection and underlying disorders, who usually are already hospitalized when infection starts. Endocarditis and secondary disease foci affect only 10% of such patients, and the relapse rate is lower than in the second group. The second group comprises young patients without identifiable primary infection; they usually have community-acquired bacteremia due to drug use and a high incidence of endocarditis and metastatic foci. The mechanisms responsible for spreading to the meninges are not fully understood. Sustained bacteremia is important but not the sole mechanism responsible for CNS invasion.

The site of CNS invasion during septicemia is still not clear. It may involve the dural venous system or choroid plexus, where receptors for pathogens have been found. Transcytosis through microvascular endothelial cells is another possible mechanism of meningeal invasion during meningitis. Once bacteria are in the subarachnoid space, host mechanisms are inadequate to control the infection. Meningeal inflammation increases CSF complement concentrations. However, complement concentration is still insufficient and, despite the increased number of leukocytes, opsonic and bactericidal activity are suboptimal, leading to multiplication of bacteria in the CSF.

Once bacteria enter and replicate within the CSF, inflammation of the subarachnoid space ensues because of bacterial (eg, cell wall components) and host factors (eg, prostaglandins, tumor necrosis factor alpha). Alteration of blood-brain barrier permeability leads to cerebral edema and increased intracranial pressure. Meningitis also modifies blood flow throughout the subarachnoid space, resulting in vasculitis and ischemia. Oxygen radicals may contribute to the increased water content, increased intracranial pressure, and changes in blood flow seen in meningitis.