eMedicine Specialties > Neurology > Neurological Infections

Staphylococcal Meningitis

Author: Lawrence A Zumo, MD, Neurologist, Private Practice
Coauthor(s): Francisco de Assis Aquino Gondim, MD, MSc, PhD, Professor Adjunto II, Departments of Physiology and Pharmacology, Neurology Residency Program Director, Faculdade de Medicina, Universidade Federal do Ceará, Brazil; Alan Greenberg, MD, Director, Associate Professor, Department of Internal Medicine, Jersey City Medical Center, Seton Hall University
Contributor Information and Disclosures

Updated: Mar 27, 2007

Introduction

Background

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. When staphylococcal endocarditis is the source, blood cultures and peripheral and echocardiographic manifestations will point to that etiology.

Pathophysiology

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. 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. 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.

Frequency

United States

In the United States, S aureus meningitis accounts for 1-3% of cases of meningitis and is associated with a high mortality rate (about 50% in adults); however, the prognosis for CSF shunt infections is more favorable.

International

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 Staphylococcus epidermidis.

In one study, 38 of 154 (25%) cases of bacterial meningitis during a 7-year period were nonpneumococcal gram-positive coccal infections. The majority of cases were due to S aureus and S epidermidis. In another study, S aureus was present in 21 of 720 (3%) cases of meningitis. Thirteen of the 21 cases were patients in the postoperative period after a neurosurgical procedure, and 3 of the remaining 8 patients had endocarditis or a parameningeal focus of infection.

Mortality/Morbidity

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.

Race

Data not available

Sex

Data not available

Age

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.

Clinical

History

With a high index of suspicion, making the diagnosis of bacterial meningitis, in general, is not difficult. All febrile patients with lethargy, headache, or confusion of sudden onset, even if fever is only low grade or the patient is a confused alcoholic, should undergo an urgent lumbar puncture, since a definitive diagnosis of meningitis can be made only by examination of CSF. In patients who have not undergone a neurosurgical procedure, presentation of S aureus meningitis may be similar to that of other types of bacterial meningitis. Patients with septicemia have additional systemic signs and symptoms, including septic shock.

• Shunt infections can be insidious, although a fulminant postoperative course can be seen with S aureus infection. Coagulase-negative staphylococci (CoNS) are normal inhabitants of the human skin and mucous membranes. Patients most at risk for CoNS infection frequently have a disruption in their host defense mechanisms due to surgery, foreign body placement, or immunosuppression. Because CoNS are common contaminants of cultures, the diagnostic definition of adult CoNS meningitis is different from the meningitis caused by other common pathogens and, hence, is defined with a more strict criteria.
  • Common presentations include low-grade fever in 14-92% of cases, malaise, poor feeding, and irritability. Signs of meningeal irritation are not usually present, since no functional communication exists between the infected ventricles and CSF spaces in most of the cases.
  • Redness of the skin overlying the shunt, if it occurs, is a highly specific sign. Infections with symptoms referable to the distal portion of the shunt are more specific: shunts that end in a vessel lead to bacteremia, while shunts that end in the pleural or peritoneal space cause peritonitis or pleuritis.
  • In immunosuppressed patients, the classical meningeal signs may be absent.
• In IV drug users, S aureus from bacterial vegetations on cardiac valves is most commonly the starting point for systemic involvement and meningitis.
• In one clinical series, CoNS were reported to be 52.8% of pathogens of ventriculoperitoneal shunt infections in pediatric patients younger than 8 years. Data on adult CoNS meningitis were not given as these had not been specifically examined in the literature.

Physical

• Classic signs include the following:
  • Neck stiffness
  • Altered consciousness (drowsiness, confusion, stupor, coma)
  • Generalized or focal seizures
  • Brudzinski sign (flexion at the hip and knee in response to forced flexion of the neck)
  • Kernig sign (inability to completely extend the legs)
• In S aureus septicemia, look for signs of systemic embolization/seeding, which include Roth spots, Janeway lesions, petechiae, subconjunctival hemorrhages, and cardiac murmurs.

Causes

• Hospitals with active neurosurgical services generate more cases of staphylococcal meningitis (eg, infection of CSF shunts) than other clinical facilities.
• In one study, 38 of 154 (25%) cases of bacterial meningitis during a 7-year period were nonpneumococcal gram-positive coccal infections; the majority of cases were due to S aureus and S epidermidis.

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