Staphylococcal Meningitis

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 (eg, cerebrospinal fluid [CSF] shunts), trauma, or underlying conditions, such as the following:

• Malignancy

• Decubitus ulcers

• Cellulitis

• Infected intravascular grafts

• Chronic alcoholism

• Diabetes mellitus

• Osteomyelitis

• Perirectal abscess

See Meningitis for a complete discussion of treatment strategies.

Staphylococci known to cause meningitis

In one study, 38 of 154 (25%) cases of bacterial meningitis during a 7-year period were nonpneumococcal, gram-positive coccal infections. Most cases were due to S aureus and S epidermidis. ^[1]  In another clinical case series of 33 patients with meningitis, spanning a decade, at a single urban teaching hospital, S aureus was found to be the causative agent in 12 (36%) of the cases by using CSF cultures, PCR, and accessory gene regulator typing. ^[2]

In yet another clinical series, coagulase-negative staphylococcus (CoNS) was reported to make up 52.8% of pathogens of ventriculoperitoneal shunt infections in pediatric patients younger than 8 years. Data on adult CoNS meningitis were not given, because these had not been specifically examined in the literature.

Once bacteria enter and replicate in 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.

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. Carriers experience more postsurgical infections than do 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. After penetration and complement activation, S aureus is coated by C3b, immunoglobulin G (IgG), or both (opsonization).

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. Attachment of S aureus to foreign surfaces involves interaction with proteins of the extracellular matrix, including fibrinogen, fibronectin, laminin, thrombospondin, vitronectin, elastin, bone sialoprotein, and collagen. The resident phagocytic population close to the foreign body is not able to kill the invading strain. Moreover, anchoring of S aureus to foreign substances modifies its susceptibility to antimicrobial agents. These factors explain the inability of antibiotics alone to eradicate foreign body infection.

The site of central nervous system (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 activities are suboptimal, leading to multiplication of bacteria in the CSF.

In IV drug users, S aureus from bacterial vegetations on cardiac valves is most commonly the starting point for systemic involvement and meningitis.

Sources of S aureus bacteremia

Patients with S aureus bacteremia can be characterized as belonging to 1 of 2 groups. In the first group, the bacterium is introduced during surgery, through trauma, or via local spreading (especially coagulase-negative staphylococci) from contiguous infection.

In the second group of patients, composed of individuals with hematogenous or spontaneous meningitis, S aureus is disseminated systemically. Infection is more often community acquired in these patients, and the incidence of positive blood culture results is higher, as is mortality rate.

Hospitals with active neurosurgical services generate more cases of staphylococcal meningitis (eg, infection of CSF shunts) than do other clinical facilities.

Groups at risk for S aureus

A particularly high rate of S aureus carriers is found in the following groups:

• Health professionals

• Patients with dermatologic conditions or human immunodeficiency virus (HIV) infection

• Intravenous (IV) drug users

• Trauma patients

• Individuals with diabetes receiving insulin injections, hemodialysis, or peritoneal dialysis

Staphylococcal meningitis is uncommon in immunocompetent individuals in the absence of focal infection (eg, pneumonia, osteomyelitis, endocarditis, parameningeal infection, psoas ^[3] or epidural abscess, sinusitis, tropical pyomyositis ^[4] ), neurosurgical interventions, or congenital dermal sinus.

The development of nosocomial staphylococcal meningitis is subsequent to central nervous system conditions and interventions, which include hematoma, ventriculo-peritoneal shunts and other embedded devices, tumors, and spinal anesthesia. In a recent case series, out of 62 patients, 37 cases were due to Staphylococcal aureus and 25 cases due to coagulase-negative Staphylococci. ^[5]

Higher mortality (36% in one clinical series) has a higher association with community-acquired staphylococcal meningitis. S aureus hematogenous meningitis has devastating clinical consequences and elevated mortality rates, especially if it is community acquired. ^[6]

Frequency of S aureus meningitis in the United States

In the United States, S aureus meningitis accounts for 1-6% of cases of meningitis. ^{[7, 8]}

International frequency of S aureus meningitis

Worldwide, S aureus meningitis constitutes 0.3-8.8% of all cases of bacterial meningitis. Hospitals with active neurosurgical services generate more cases of staphylococcal meningitis (eg, infection of CSF shunts). S aureus is the second most common cause of CSF shunt infections, outnumbered only by S epidermidis.

Age differences in incidence

Newborn nurseries seem to experience waves of staphylococcal epidemics that occur in cycles (ie, epidemics occurred in the 1900s, late 1920s, early 1950s, early 1970s, late 1980s, and early 1990s). S aureus was the most common staphylococcal pathogen in the nursery from the 1950s to the 1970s.

Mortality and morbidity rates

Staphylococcal meningitis is associated with a high mortality rate (about 50% in adults), particularly hematogenous S aureus meningitis (mortality rate, 18-56%). The prognosis for CSF shunt infections is more favorable, probably because of earlier recognition. (Shunt infections can be insidious, although a fulminant postoperative course can be seen with S aureus infection.)

Patients in whom the bacteria is introduced during surgery or by trauma or local spreading (especially coagulase-negative staphylococci) from contiguous infection have a lower mortality rate than do patients with hematogenous meningitis; this may be explained by early recognition and less systemic involvement in the nonhematogenous meningitis patients.

Any localized S aureus infection can lead to bacteremia. In the pre-antibiotic era, the mortality rate was 82%. Studies have since reported mortality rates of 30-40% in non–drug-using patients with S aureus septicemia.

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Untreated bacterial meningitis is usually fatal. A disproportionate number of deaths occur in infants and elderly persons, with the mortality rate being highest in neonates. However, the prognosis for patients with CSF shunt infections is more favorable.

The presence of bacteremia, coma, seizures, or various underlying diseases (eg, alcoholism, diabetes mellitus, multiple myeloma, head trauma) significantly worsens the prognosis; therefore, an aggressive approach should be used in these settings.

The likelihood of either disability in or complete recovery of the patient, as well as of future employability, depends on the underlying condition and the severity of the meningitis.