Central Nervous System (CNS) Infections
- Infections are the result of hematogenous spread from a primary infection site, seeding from a parameningeal focus, reactivation from a latent site, trauma, or congenital defects in the CNS.
- CNS infections may be caused by a variety of bacteria, fungi, viruses, and parasites. The most common causes of bacterial meningitis include Streptococcus pneumoniae, Neisseria meningitides, Listeria monocytogenes, and Haemophilus influenzae.
- The critical first step in the acquisition of acute bacterial meningitis is nasopharyngeal colonization of the host by the bacterial pathogen. The bacteria must first attach themselves to nasopharyngeal epithelial cells through structures called lectins. The bacteria are then phagocytized across nonciliated columnar nasopharyngeal cells into the host’s bloodstream.
- A common characteristic of most CNS bacterial pathogens (e.g., H. influenzae, Escherichia coli, and N. meningitidis) is the presence of an extensive polysaccharide capsule that is resistant to neutrophil phagocytosis and complement opsonization.
- The exact site and mechanism of bacterial invasion into the CNS is unknown; however, studies suggest that invasion into the subarachnoid space occurs by continuous exposure of the CNS to large bacterial innocula.
- Bacterial cell death then causes the release of cell wall components such as lipopolysaccharide (LPS), lipid A (endotoxin), lipoteichoic acid, teichoic acid, and peptidoglycan depending on whether the pathogen is gram-positive or gram-negative. These cell wall components cause capillary endothelial cells and CNS macrophages to release cytokines (interleukin-1 [IL-1], tumor necrosis factor [TNF], and other inflammatory mediators). Products of the cyclooxygenase-arachidonic acid pathway (prostaglandins and thromboxanes) and platelet activating factor (PAF) are also released. PAF activates the coagulation cascade, and arachidonic acid metabolites stimulate vasodilatation. These lead to cerebral edema, elevated intracranial pressure, cerebrospinal fluid (CSF) pleocytosis, disseminated intravascular coagulation (DIC), syndrome of inappropriate antidiuretic hormone secretion (SIADH), decreased cerebral blood flow, cerebral ischemia, and death.
- Purpuric and petechial skin lesions typically indicate meningococcal involvement, although the lesions may be present with H. influenzae meningitis. Rashes rarely occur with pneumococcal meningitis.
- Waterhouse-Friderichsen syndrome, a rapid eruption of multiple hemorrhagic lesions associated with a shocklike state, is associated with meningococcal meningitis.
- H. influenza meningitis and meningococcal meningitis both can cause involvement of the joints during the illness.
- A history of head trauma with or without skull fracture or presence of a chronically draining ear is associated with pneumococcal involvement.
- Several tubes of CSF are collected via lumbar puncture for chemistry, microbiology, and hematology tests. Theoretically, the first tube has a higher likelihood of being contaminated with both blood and bacteria during the puncture, although the total volume is more important in practice than the tube cultured. CSF should not be refrigerated or stored on ice.
- Analysis of CSF chemistries typically includes measurement of glucose and total protein concentrations. An elevated CSF protein of 100 mg/dL or greater and a CSF glucose concentration of less than 50% of the simultaneously obtained peripheral value suggest bacterial meningitis.
- The values for CSF glucose, protein, and WBC concentrations found with bacterial meningitis overlap significantly with those for viral, tuberculous, and fungal meningitis. Therefore, CSF WBC counts and CSF glucose and protein concentrations cannot always distinguish the different etiologies of meningitis.
Empiric antimicrobial therapy should be instituted as soon as possible to eradicate the causative organism. Antimicrobial therapy should last at least 48 to 72 hours or until the diagnosis of bacterial meningitis can be ruled out.
Antibiotic dosages for treatment of CNS infections must be maximized to optimize penetration to the site of infection.
Menigitis caused by S. pneumoniae and H. influenzae is successfully treated with 10 to 14 days of antibiotic therapy. Meningitis caused by N. meningitides usually can be treated with a 7-day course. A longer course, 14 to 21 days, is recommended for patients infected with Listeria monocytogenes, group B streptococcus, and enteric gram-negative bacilli. Therapy should be individualized, and some patients may require longer courses.
Isolation and identification of the causative agent can direct the selection of the most appropriate antimicrobial therapy for the patient.
With increased meningeal inflammation, there will be greater antibiotic penetration. Problems of CSF penetration may be overcome by direct instillation of antibiotics by intrathecal, intracisternal, or intraventricular routes of administration.