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Meningitis is an infection of the meninges, the membranes that line the brain and spinal cord (Figure 72–1). Meningitis can be categorized as acute, subacute, or chronic depending on the speed of onset of the initial presentation and the rate of progression of the illness. Acute meningitis is caused by either pyogenic bacteria, such as Streptococcus pneumoniae and Neisseria meningitidis, or viruses, such as Coxsackie virus and herpes simplex virus type 2 (HSV-2). Viral meningitis is often called aseptic meningitis because routine cultures for bacterial pathogens are negative. Subacute meningitis is caused by Mycobacterium tuberculosis and fungi, such as Cryptococcus. The causative organisms are often found in the spinal fluid located in the subarachnoid space.
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Hematogenous spread (i.e., bacteremia or viremia) is the most common route by which organisms reach the meninges. Direct spread via adjacent infections, such as otitis media and sinusitis; via neurosurgery, such as a shunt to relieve hydrocephalus; or via trauma, such as a fracture of the cribriform plate, occurs less frequently. The importance of hematogenous spread is emphasized by the success of the conjugate vaccines against S. pneumoniae, N. meningitidis, and Haemophilus influenzae type B that induce circulating IgG antibodies that neutralize the bacteria in the blood.
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Acute bacterial meningitis begins with nasopharygeal colonization followed by local invasion, entry into the bloodstream, and invasion of the meninges (Figure 72–2). This is followed by an inflammatory response that causes many of the clinical manifestations, especially the edema resulting in increased intracranial pressure leading to headache. Cerebral vasculitis and infarction can also occur.
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Clinical Manifestations
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Early symptoms include the classic triad of fever, headache, and stiff neck (nuchal rigidity). Altered mental status also commonly occurs. If untreated, meningitis may progress to vomiting, seizures, photophobia, and focal neurologic deficits. Different pathogens can present with different rates of clinical progression, from acute onset and rapid progression (hours to days) to subacute or chronic onset and slow progression (days to weeks). N. meningitidis infection can be associated with disseminated disease (meningococcemia) and result in petechial rash and ultimately purpura fulminans (Figure 72–3).
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Bacterial Pathogens Causing Acute Meningitis
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The most common bacterial cause of acute meningitis overall is S. pneumoniae. However, Streptococcus agalactiae (group B Streptococcus) predominates in neonates, and N. meningitidis is common in teenagers and young adults (Table 72–2).
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H. influenzae type B used to be an important cause in young children, but the widespread use of the conjugate polysaccharide vaccine has greatly decreased its incidence. Listeria monocytogenes is reasonably common in the very young, the very old, and immunocompromised patients. Less common pathogens include Borrelia burgdorferi (Lyme disease) and Treponema pallidum (syphilis).
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Viral Pathogens Causing Acute Meningitis
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The most common viral causes of acute meningitis are enteroviruses such as Coxsackie virus, echovirus, and enterovirus 71. Enteroviral meningitis occurs primarily in young children, and the peak incidence is in the summer and fall seasons.
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HSV-2 is also a common cause of meningitis. Note that HSV-2 typically causes meningitis, whereas herpes simplex virus type 1 (HSV-1) causes encephalitis. Primary genital infections with HSV-2 are more likely to result in meningitis than recurrent HSV-2 infections. Primary and reactivation varicella-zoster virus (VZV) infection can also be associated with meningitis.
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Although arboviruses typically cause encephalitis, arboviruses such as West Nile virus (WNV) and St. Louis encephalitis virus can also cause meningitis. Mumps virus used to be a common cause of meningitis, but widespread use of the mumps vaccine has greatly reduced its incidence.
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Pathogens Causing Subacute and Chronic Meningitis
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The most common causes of subacute and chronic meningitis are M. tuberculosis and fungi such as Cryptococcus, Coccidioides, and Histoplasma. Cryptococcal meningitis occurs most commonly in immunocompromised patients, such as those with acquired immunodeficiency syndrome (AIDS), but can cause subacute and chronic meningitis in immunocompetent patients as well. Other causes of chronic meningitis include T. pallidum and B. burgdorferi. Human immunodeficiency virus (HIV) is the most common viral cause of chronic meningitis.
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A microbiologic diagnosis of acute bacterial meningitis is typically made by Gram stain and culture of CSF. However, PCR-based tests are being increasingly used because they yield results rapidly and with great accuracy. For example, a PCR-based panel is now available that tests for the presence in spinal fluid of six common bacteria, seven common viruses, and the yeast Cryptococcus with a turnaround time of 1 hour.
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Analysis of spinal fluid can distinguish between acute bacterial meningitis and viral meningitis (see Table 72–1). While they both tend to have elevated white blood cells (WBCs) and protein in CSF, bacterial infections tend to be neutrophil predominant, whereas viral infections are lymphocyte predominant. Bacterial infections are associated with low glucose concentrations in CSF, whereas viral infections have normal glucose levels.
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Subacute and chronic meningitis tend to be lymphocyte predominant with very high protein levels and low glucose. Viral infections are often diagnosed by using PCR assay for viral DNA or RNA in CSF or by serologic tests for specific antibody. Gram stain and bacteriologic cultures of CSF are negative in viral meningitis. Fungal infections can be diagnosed by culture or by serologic tests. In the case of Cryptococcus, the India ink test and the cryptococcal antigen test are also useful.
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Empiric therapy for acute bacterial meningitis must include drugs with excellent penetration into the CSF (able to pass the blood–brain barrier), that are bactericidal, and that are active against the most common pathogens. In older children and adults, ceftriaxone or cefotaxime plus vancomycin is a common empiric regimen. Vancomycin is added to cover for penicillin- or cephalosporin-resistant pneumococci. Ampicillin should be added if Listeria is a likely cause.
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Empiric therapy for neonatal bacterial meningitis includes ampicillin plus either ceftriaxone or cefotaxime, with or without gentamicin. Acyclovir is used for the treatment of HSV and VZV infection.
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Prevention strategies include both immunization and chemoprophylaxis. Vaccines are effective in preventing bacterial meningitis, caused by S. pneumoniae, N. meningitidis, and H. influenzae type B. The immunogen in the conjugate vaccines is the capsular polysaccharide of the organism.
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The current conjugate pneumococcal vaccine (Prevnar 13) protects against the 13 most common serotypes. The current conjugate H. influenzae vaccine protects only against the type B serotype.
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The current conjugate meningococcal vaccine protects against four common serotypes (A, C, Y, and W-135). Note, however, it does not contain the type B polysaccharide. The vaccine against type B meningococcus contains factor H binding protein (fHbp) as the immunogen. A second vaccine against type B meningococci containing four surface proteins (fHbp, NadA, NHBA, and PorA) is also available.
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Chemoprophylaxis against S. agalactiae (group B Streptococcus) is aimed at reducing vaginal carriage in the mother. If vaginal or rectal cultures are positive at 35 to 37 weeks of gestation, then ampicillin should be given. Chemoprophylaxis is also used to reduce nasopharyngeal carriage of N. meningitidis and H. influenzae type B. Close contacts of patients with meningitis caused by these organisms should receive either ciprofloxacin for Neisseria or rifampin for Haemophilus.