Acute Bacterial Meningitis
Acute bacterial meningitis is a fulminant, often fatal pyogenic infection beginning in the meninges. Symptoms include headache, fever, and stiff neck. Without rapid treatment, obtundation and coma follow. Diagnosis is by CSF tests. Treatment requires antibiotics, often beginning empirically with a 3rd- or 4th-generation cephalosporin, vancomycin, and ampicillin; corticosteroids are usually given. Residual morbidity is common.
Many bacteria can cause meningitis, but the most common are
Meningococci exist in the nasopharynx of about 5% of people and spread by respiratory droplets and close contact. Only a small fraction of carriers develop meningitis; what makes them susceptible is unknown. Meningococcal meningitis occurs most often during the first year of life. It also tends to occur in epidemics among closed populations (eg, in military barracks, college dormitories, and boarding schools).
Pneumococci are the most common cause of meningitis in adults. Especially at risk are alcoholics and people with chronic otitis, sinusitis, mastoiditis, CSF leaks, recurrent meningitis, pneumococcal pneumonia, sickle cell disease, or asplenia. Incidence of pneumococcal meningitis is decreasing because of routine vaccination.
Gram-negative organisms (most often Escherichia coli, Klebsiella sp, or Enterobacter sp) can cause meningitis in infants, in immunocompromised patients, or after CNS surgery, CNS trauma, bacteremia (eg, due to GU manipulation), or hospital-acquired infections. Pseudomonas sp occasionally causes meningitis in immunocompromised or colonized patients. Haemophilus influenzae type b meningitis, now uncommon because of widespread vaccination, can occur in immunocompromised patients or after head trauma in unvaccinated people.
Staphylococci can cause meningitis after penetrating head wounds or neurosurgical procedures (often as part of a mixed infection) or after bacteremia (eg, due to endocarditis).
Listeria typically cause meningitis in the very young, the very old, and patients of any age who are immunocompromised because of chronic renal failure, hepatic disorders, or corticosteroid or cytotoxic therapy after organ transplantation.
Bacteria typically reach the meninges by hematogenous spread from sites of colonization in the nasopharynx or other foci of infection (eg, pneumonia). Why some bacteria are more prone to colonize CSF is not clear, but binding pili and encapsulation appear to play a role. Receptors for pili and other bacterial surface components in the choroid plexus facilitate penetration into CSF.
Bacteria can also enter CSF by direct extension from nearby infections (eg, sinusitis, mastoiditis) or through exterior openings in normally closed CSF pathways (eg, due to meningomyelocele, spinal dermal sinus, penetrating injuries, or neurosurgical procedures).
Bacterial surface components, complement, and inflammatory cytokines (eg, tumor necrosis factor, IL-1) draw neutrophils into the CSF space. The neutrophils release metabolites that damage cell membranes including those of the vascular endothelium. The result is vasculitis and thrombophlebitis (which cause focal ischemia or infarction) and brain edema. Vasculitis also disrupts the blood-brain barrier, further increasing brain edema. The purulent exudate in the CSF blocks CSF reabsorption by the arachnoid villi, causing hydrocephalus. Brain edema and hydrocephalus increase intracranial pressure.
Systemic complications include
- Hyponatremia due to the syndrome of inappropriate antidiuretic hormone (SIADH)
- Disseminated intravascular coagulation (DIC)
- Septic shock
Occasionally, bilateral adrenal hemorrhagic infarction (Waterhouse-Friderichsen syndrome) results, particularly with meningococcal infection.
Symptoms and Signs
A respiratory illness or sore throat often precedes the more characteristic symptoms of fever, headache, stiff neck, and vomiting. Kernig's and Brudzinski's signs appear in about half of patients. Adults may become desperately ill within 24 h, and children even sooner. Seizures occur in about 30%. Cranial nerve abnormalities (eg, 3rd [oculomotor] or 7th [facial] cranial nerve palsy; occasionally, deafness) and other focal deficits occur in 10 to 20%. In patients > 2 yr, changes in consciousness progress through irritability, confusion, drowsiness, stupor, and coma. Opisthotonic posturing may occur.
Dehydration is common, and vascular collapse causes shock. Infection, particularly meningococcal, may be disseminated widely, to the joints, lungs, sinuses, and elsewhere. A petechial or purpuric rash commonly occurs in meningococcal meningitis. Examination of the head, ears, spine, and skin may reveal a source or route of infection. Spinal dimples, nevi, or tufts of hair suggest a spinal dermal sinus that communicates with the meninges and provides a portal for bacteria entry.
Young children: In children < 2 yr, meningeal signs may be absent. In those < 2 mo, symptoms and signs are often nonspecific, particularly in early disease. Fever, hypothermia, poor feeding, lethargy, vomiting, and irritability are common presenting symptoms. Seizures, a high-pitched cry, and bulging or tight fontanelles are possible but often occur late. Subdural effusions may develop after several days; typical signs are seizures, persistent fever, and enlarging head size.
Elderly: The elderly may also have nonspecific symptoms (eg, confusion with or occasionally without fever). Meningeal signs may be absent or mild. Arthritis may restrict neck motion, often in multiple directions, and should not be mistaken for meningismus.
Patients with partially treated meningitis: Patients seen early in the disease, before typical findings of meningitis appear, are sometimes diagnosed with otitis media or sinusitis and given oral antibiotics. Depending on the drug, the infection may be partially (but temporarily) suppressed. Patients may appear less ill and have milder meningeal signs and slower disease progression. This situation can significantly hamper recognition of meningitis.
Acute bacterial meningitis is suspected in children < 2 yr with lethargy, progressive irritability, a high-pitched cry, a bulging fontanelle, meningeal signs, or hypothermia. Signs are often nonspecific, and threshold for suspecting meningitis must be low. Meningitis is suspected in patients > 2 yr with meningeal signs or unexplained alterations in consciousness, particularly in those with fever or risk factors.
Because acute bacterial meningitis, especially meningococcal, can be lethal within hours, it must be treated as soon as the diagnosis is suspected. Blood is drawn for culture, Gram stain, and bacterial DNA PCR if available. Prompt lumbar puncture with or without prior CT is required, but these procedures should not delay immediate treatment with corticosteroids and antibiotics.
CSF tests: CSF pressure may be elevated. Gram stain shows organisms in CSF in 80% of patients with acute bacterial meningitis. CSF contains a predominantly neutrophilic WBC count, usually between 1,000 μL and 10,000/μL. Glucose is usually < 40 mg/dL because of impaired CNS glucose transport and glucose consumption by neutrophils and bacteria. Protein is typically > 100 mg/dL. Cultures are positive in 90%; they may be falsely negative in patients who are partially treated. Latex agglutination tests can be used to detect antigens of meningococci, H. influenzae type b, pneumococci, group B streptococci, and E. coli K1 strains. However, these tests are not always routinely done because they probably add little to other routine CSF tests. The limulus amebocyte lysate test can detect endotoxin in gram-negative meningitis. This test and the latex agglutination tests may be helpful when patients have received prior antibiotics (partial treatment), when patients are immunocompromised, or when other CSF tests do not identify the causative organism. Broad range bacterial PCR for 16S ribosomal DNA testing can be useful if CSF cultures detect no organisms. PCR testing is also available for meningococcus and pneumococcus.
Imaging tests: CT, when done, may be normal or show small ventricles, effacement of the sulci, and contrast enhancement over the convexities. MRI with gadolinium is more sensitive for subarachnoid inflammation. Scans should be scrutinized for evidence of brain abscess, sinusitis, mastoiditis, skull fracture, and congenital malformations. Evidence of venous infarctions or communicating hydrocephalus may appear after days or weeks.
Other tests: Peripheral blood tests include blood cultures (positive in 50%), cell count with differential, electrolytes, glucose, renal function, coagulation tests, and PCR for bacterial pathogens (where available). Serum Na is monitored for evidence of SIADH, and coagulation results are monitored for evidence of DIC. Urine and any nasopharyngeal or respiratory secretions and skin lesions are cultured.
Alternate diagnoses: Disorders that resemble bacterial meningitis can usually be differentiated by clinical presentation, neuroimaging, and routine CSF tests.
Viral meningitis can cause fever, headache, and stiff neck, but patients do not appear as ill, and CSF test results are different (see Table 1: Meningitis: Cerebrospinal Fluid Abnormalities in Various Infections).
Viral encephalitis, especially herpes encephalitis, also causes fever, headache, confusion, seizure and coma, which can be confused with bacterial meningitis. MRI and CSF testing are helpful in distinguishing viral encephalitis from bacterial meningitis. Serum procalcitonin and C-reactive protein are elevated to a much greater degree with bacterial than with viral infections.
Subarachnoid hemorrhage causes severe headache and a stiff neck, but onset is explosive and fever is usually absent; CT shows hemorrhage, or the CSF contains RBCs or is xanthochromic.
Brain abscess can cause fever, headache, and impaired consciousness, but the neck is typically supple unless abscess contents have ruptured into the CSF space, causing a fulminant secondary meningitis.
Severe systemic infections (eg, sepsis, infective endocarditis) can impair cognition or consciousness by causing fever and compromising tissue perfusion; CSF is normal or contains a small number of WBCs, and the neck is supple.
Cerebellar tonsillar herniation can cause impaired consciousness (secondary to obstructive hydrocephalus) and neck stiffness but usually not fever, and it can be differentiated by CT or MRI.
Cerebral vasculitis (eg, due to SLE) and cerebral venous thrombosis can cause mild fever, headache, altered mental status, and mild to moderate meningeal inflammation, typically producing CSF test results similar to those of viral encephalitis.
Fungal meningitis or amebic ( Naegleria ) meningoencephalitis occasionally causes acute, fulminant meningitis with clinical findings and routine CSF test results similar to those of bacterial meningitis. Gram stain and routine cultures show no bacteria. In such cases, CSF is checked for cryptococcal polysaccharide antigen, Histoplasma polysaccharide antigen, and Coccidioides immitis complement fixation antibodies; CSF is also examined using India ink and cultured for fungi. In amebic meningoencephalitis, ameboid movement can be detected in unspun wet mounts of CSF, and the amebas can be cultured.
TB meningitis is usually subacute or chronic but is occasionally acute; CSF characteristics are usually intermediate between those of acute bacterial and aseptic meningitis. Special stains (eg, acid-fast, immunofluorescent) and PCR are needed to identify TB.
Waterhouse-Friderichsen syndrome: This disorder should be suspected in any febrile patient who remains in shock despite adequate volume replacement and who has rapidly evolving purpura and evidence of DIC. With hemorrhagic necrosis of the adrenal glands, adrenocorticol insufficiency develops rapidly. A serum cortisol level < 13 ug/dL (in combination with an increased ACTH level) suggests glucocorticoid deficiency due to primary adrenal insufficiency. CT, MRI, or ultrasonography of the adrenal glands is done.
Immediate empirical treatment with corticosteroids, antibiotics, and supportive care have improved outcome and reduced mortality to < 10%. However, if meningitis is treated late or occurs in neonates, the elderly, or immunocompromised patients, death is common. A poor outcome is predicted by persistent leukopenia or development of Waterhouse-Friderichsen syndrome. Survivors occasionally have deafness, other cranial nerve deficits, cerebral infarction, recurrent seizures, or intellectual disability.
- Antibiotics (eg, ampicillin Some Trade Names:
PRINCIPEN, and ceftriaxone Some Trade Names
ROCEPHIN, with or without vancomycin Some Trade Names
If acute bacterial meningitis is suspected, corticosteroids and antibiotics are given as soon as blood cultures are drawn (see Table 2: Meningitis: Antibiotic Therapy for Acute Bacterial Meningitis). If the diagnosis is unclear and the patient does not appear ill, antibiotics may be withheld pending CSF test results. Giving antibiotics before lumbar puncture slightly increases the probability of false-negative cultures, particularly with pneumococci, but does not affect other test results.
Corticosteroids: Dexamethasone .15 mg/kg IV q 6 h in children and 10 mg IV q 6 h in adults should be given with the first dose of antibiotics and continued for 4 days. Dexamethasone may prevent hearing loss and other neurologic sequelae by inhibiting release of proinflammatory cytokines triggered by antibiotic-induced bacterial lysis. Because corticosteroids impede vancomycin's penetration into CSF, vancomycin is given in a higher dose—15 to 20 mg/kg q 8 h.
In immunocompromised patients, the benefits of Dexamethasone in reducing intracranial pressure must be weighed against the risk of worsening immunodeficiency.
Antibiotics: Choice of empiric antibiotics depends on the suspected pathogen and patient age (see Table 2: Meningitis: Antibiotic Therapy for Acute Bacterial Meningitis; for antibiotic doses, see Table 3: Meningitis: Common IV Antibiotic Dosages for Bacterial Meningitis*).
Third-generation cephalosporins (eg, ceftriaxone, cefotaxime) are effective against pathogens common in patients of all ages., a 4th-generation cephalosporin, can be substituted for a 3rd-generation cephalosporin in children and can be useful for Pseudomonas infection. However, because cephalosporin-resistant pneumococci are becoming increasingly prevalent, vancomycin, with or without rifampin, is usually added. Meropenemis also effective against Pseudomonas and many gram-negative bacteria. Ampicillinis added to cover Listeria sp. Aminoglycosides penetrate the CNS poorly but are still used empirically to cover gram-negative bacteria in neonates (see Infections in Neonates: Treatment). When meningitis due to a gram-negative anaerobe is a consideration (eg, because of otitis, sinusitis or mastoiditis), meropenem should be added. For meningitis patients with a recent neurosurgical procedure or with an intraventricular shunt, vancomycin, meropenem, plus metronidazoleprovide coverage against staphylococci, gram-negative bacteria, and anaerobes.
Because herpes encephalitis can resemble bacterial meningitis at presentation, acyclovir is usually included with the initial empirical therapy. Similarly, during tick season, may be added to cover CNS infection with Rocky Mountain spotted fever.
Reevaluation: As the results of blood, CSF, and other tests become available and the pathogen and drug susceptibility are identified, antibiotics are adjusted accordingly.
If no pathogen is identified in the CSF, addition of antibiotics for TB should be considered, especially if CSF glucose levels are very low.
If no bacteria grow in culture or are otherwise identified after 24 to 48 h, corticosteroids are stopped; corticosteroids continued for > 1 day without appropriate antibiotic coverage could worsen the infection. When initial CSF tests are inconclusive, a repeat lumbar puncture in 8 to 24 h (or sooner if the patient deteriorates) may help. If clinical and CSF findings continue to suggest aseptic meningitis, antibiotics are withheld. If the patient's condition is serious, especially if antibiotics have been given (possibly causing falsely sterile cultures), antibiotics should be continued.
Lumbar puncture should be repeated 24 to 48 h after starting antibiotics to confirm CSF sterility and conversion to lymphocytic predominance. Generally, antibiotics are continued for ≥ 1 wk after fever subsides and CSF is nearly normal (complete normalization may take weeks). Drug doses are not reduced when clinical improvement occurs because drug penetration commonly decreases as meningeal inflammation decreases.
Other measures: Supportive therapy includes treatment of fever, dehydration, electrolyte disorders, seizures, and shock.
If Waterhouse-Friderichsen syndrome is suspected, high-dose hydrocortisone(eg, 100 to 200 mg IV q 4 to 6 h or as a continuous infusion after an initial bolus) is given; treatment should not be delayed pending measurement of hormone levels.
Cerebral edema can be minimized by avoiding overhydration. If brain herniation is suspected, hyperventilation (Paco2, 25 to 30 mm Hg acutely), mannitol, and additional dexamethasone(4 mg IV q 4 h) can be used; barbiturate-induced coma may be considered. Monitoring intracranial pressure may be helpful. If ventricles are enlarged, intracranial pressure may be monitored and CSF drained, but outcome is usually poor.
If infants up to 1 yr of age have subdural effusion, daily subdural taps through the cranial sutures usually help. No more than 20 mL/day of CSF should be removed from one side to avoid sudden shifts in intracranial contents. If effusion persists after 3 to 4 wk of taps, surgical exploration for possible excision of a subdural membrane is indicated.
Patients with severe meningococcal meningitis may benefit from drotrecogin alfa activated protein C), which downregulates the inflammatory response. In patients with sepsis due to meningitis, intracranial bleeding occurs more frequently, with or without drotrecogin alfa treatment.
Physical measures: Spread of meningitis is prevented by keeping patients in respiratory isolation (droplet precautions) for the first 24 h of therapy. Gloves, masks, and gowns are used.
Vaccinations: Certain types of bacterial meningitis can be prevented by vaccination.
A conjugated pneumococcal vaccine effective against 7 serotypes, including > 80% of organisms that cause meningitis, is recommended for all children.
Routine vaccination against H. influenzae type b is highly effective and begins at age 2 mo.
A quadrivalent meningococcal vaccine is given to children aged 2 to 10 yr with immunodeficiencies or functional asplenia, all children at age 11 to 12 yr (and older children, college students living in dormitories, and military recruits who have not had the vaccine previously), travelers to endemic areas, and laboratory personnel who routinely handle meningococcal specimens. Chemoprophylaxis is given to close contacts of patients with meningococcal meningitis. During an epidemic, the population at risk must be identified (eg, college students, a small town) and its size determined before proceeding to mass vaccination. The effort is expensive and requires public education and support, but it saves lives and reduces morbidity. Note: The meningococcal vaccine does not protect against serotype B meningococcal meningitis; this information should kept in mind when a vaccinated patient presents with symptoms of meningitis.
Chemoprophylaxis: Anyone who has face-to-face contact with the patient (eg, family, medical staff members) should receive postexposure chemoprophylaxis.
For meningococcal meningitis, chemoprophylaxis consists of one of the following:
- Rifampin 600 mg (for children > 1 mo, 10 mg/kg; for children < 1 mo, 5 mg/kg) po q 12 h for 4 doses
- Ceftriaxone 250 mg (for children < 15 yr, 125 mg) IM for 1 dose
- In adults, a fluoroquinolone (ciprofloxacin Some Trade Names levofloxacin 500 mg or ofloxacin 400 mg) po for 1 dose
Chemoprophylaxis against H. influenzae type b is rifampin 20 mg/kg po once/day (maximum: 600 mg/day) for 4 days. There is no consensus on whether children < 2 yr require prophylaxis for exposure at day care.
Chemoprophylaxis is not usually needed for contacts of patients with pneumococcal meningitis.
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