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Acute bacterial meningitis is rapidly progressive bacterial infection of the meninges and subarachnoid space. Findings typically include headache, fever, and nuchal rigidity. Diagnosis is by CSF analysis. Treatment is with antibiotics and corticosteroids given as soon as possible.
For neonatal meningitis, see Infections in Neonates: Neonatal Bacterial Meningitis
Pathophysiology
Most commonly, bacteria reach the subarachnoid space and meninges via hematogenous spread. Bacteria may also reach the meninges from nearby infected structures (eg, sinuses, the middle ear) or through a congenital or acquired defect in the skull or spine (eg, a penetrating head wound, a neural tube defect, an opening made during neurosurgery).
Because WBCs, immunoglobulins, and complement are normally sparse or absent from CSF, bacteria initially multiply without causing inflammation. Later, bacteria release endotoxins, teichoic acid, and other substances that trigger an inflammatory response with mediators such as WBCs and TNF. Typically in CSF, levels of protein increase, and because bacteria consume glucose and because less glucose is transported into the CSF, glucose levels decrease.
Inflammation in the subarachnoid space is accompanied by cortical encephalitis and ventriculitis. Complications are common and may include
Etiology
Likely causes depend on
Age:
In children and young adults, the most common causes are
N. meningitidis meningitis occasionally causes death within hours. Sepsis caused by N. meningitidis sometimes results in bilateral adrenal hemorrhagic infarction (Waterhouse-Friderichsen syndrome).
Haemophilus influenzae type B, previously the most common cause of meningitis in children < 6 yr and overall, is now a rare cause in the US and Western Europe, where the H. influenzae vaccine is widely used. However, in areas where it is not widely used, H. influenzae is a common cause, particularly in children aged 2 mo to 6 yr.
In middle-aged adults and in the elderly, the most common cause of meningitis is
Less commonly, N. meningitidis causes meningitis in middle-aged and older adults. As host defenses decline with age, patients may develop meningitis due to L. monocytogenes or gram-negative bacteria.
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Table 2
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Causes of Bacterial Meningitis by Patient Age |
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Age Group
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Bacteria
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Children and young adults
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Neisseria meningitidis
Streptococcus pneumoniae
S. aureus*
Haemophilus influenzae (rare in developed countries but still seen in countries where the H. influenzae type B vaccine is not widely used)
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Middle-aged adults
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S. pneumoniae
S. aureus*
N. meningitidis (less common in this age group)
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The elderly
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S. pneumoniae
S. aureus*
Listeria monocytogenes
Gram-negative bacteria
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*S. aureus occasionally causes severe meningitis in patients of all ages, It is the most common cause of meningitis that develops after a penetrating head wound.
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Route:
Routes of entry include the following:
Having any of the above conditions increases the risk of acquiring meningitis.
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Table 3
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Causes of Bacterial Meningitis by Route |
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Route
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Bacteria
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Infection in or around the head (eg, sinusitis, otitis, mastoiditis), sometimes with a CSF leak
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Streptococcus pneumoniae
Haemophilus influenzae
Anaerobic and microaerophilic streptococci
Bacteroides sp
Staphylococcus aureus
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Penetrating head wound
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S. aureus
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Damaged skin (eg, skin infections, abscesses, pressure ulcers, large burns)
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S. aureus
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An infected shunt
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S. epidermidis
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A neurosurgical procedure
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Gram-negative bacteria (eg, Klebsiella pneumoniae, Acinetobacter calcoaceticus, Escherichia coli)
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Immune status:
Overall, the most common causes in immunocompromised patients are
But the most likely bacteria depend on the type of immune deficiency:
In very young infants (particularly premature infants) and the elderly, T-cell immunity may be weak; thus, these age groups are at risk of meningitis due to L monocytogenes.
Symptoms and Signs
In most cases, bacterial meningitis begins with 3 to 5 days of insidiously progressive nonspecific symptoms including malaise, fever, irritability, and vomiting. However, meningitis may be more rapid in onset and can be fulminant, making bacterial meningitis one of the few disorders in which a previously healthy young person may go to sleep with mild symptoms and never awaken.
Typical meningeal symptoms and signs include fever, tachycardia, headache, photophobia, changes in mental status (eg, lethargy, obtundation), nuchal rigidity (although not all patients report it), and sometimes, when Staphylococcus aureus is the cause, back pain.
Seizures occur early in up to 40% of children with acute bacterial meningitis and may occur in adults. Up to 12% of patients present in coma. Severe meningitis may cause papilledema, but papilledema may be absent early, even when ICP is increased.
Accompanying systemic infection by the organism may cause rashes, petechiae, or purpura (which suggest meningococcemia); pulmonary consolidation (often in meningitis due to S. pneumoniae); or heart murmurs (which suggest endocarditis—eg, often caused by S. aureus or S. pneumoniae).
Atypical presentations in adults :
Fever and nuchal rigidity may be absent or mild in immunocompromised or elderly patients and in alcoholics. Often, in the elderly, the only sign is confusion in those who were previously alert or altered responsiveness in those who have dementia. In such patients, starting appropriate antibiotics before head CT or MRI may be prudent.
If bacterial meningitis develops after a neurosurgical procedure, symptoms often take days to develop.
Diagnosis
As soon as acute bacterial meningitis is suspected, blood cultures and lumbar puncture for CSF analysis (unless contraindicated) are done. If the patient is very ill, antibiotics are given immediately. The need for confirmation should not delay treatment.
Clinicians should suspect bacterial meningitis in patients with typical symptoms and signs, usually fever, changes in mental status, and nuchal rigidity. However, clinicians must be aware that symptoms and signs are different in neonates and infants and may be absent or initially mild in the elderly, alcoholics, and immunocompromised patients. Diagnosis can be challenging in patients who have had a neurosurgical procedure (because such procedures can also cause changes in mental status and neck stiffness) and in the elderly and alcoholics (because changes in mental status may be due to falls and subdural hematomas).
Focal seizures or focal neurologic deficits may indicate a focal lesion such as a brain abscess.
Because untreated bacterial meningitis is lethal, tests should be done if there is even a small chance of meningitis. Testing is particularly helpful in infants, the elderly, alcoholics, immunocompromised patients, and patients who had neurosurgical procedure because symptoms may be atypical.
If findings suggest acute bacterial meningitis, routine tests include
Lumbar puncture:
Unless contraindicated, lumbar puncture is done immediately to obtain CSF for analysis, the mainstay of diagnosis.
Contraindications to immediate lumbar puncture are signs suggesting markedly increased ICP or a mass; typically, these signs include focal deficits, papilledema, deterioration in consciousness, and seizures. In such cases, lumbar puncture may cause brain herniation and thus is deferred until neuroimaging (typically contrast-enhanced CT or MRI) is done to check for increased ICP or a mass. When lumbar puncture is deferred, treatment is best begun immediately (after blood sampling for culture and before neuroimaging). After ICP, if increased, has been lowered or if no mass is detected, lumbar puncture can be done.
CSF should be sent for analysis: cell count, protein, glucose, Gram staining, culture, PCR (if available), and other tests as indicated clinically. Simultaneously, a blood sample should be drawn and sent to have the CSF:blood glucose ratio determined. CSF cell count should be determined as soon as possible because WBCs may adhere to the walls of the collecting tube, resulting in a falsely low cell count; in extremely purulent CSF, WBCs may lyse. Typical CSF findings in bacterial meningitis include increased pressure, fluid that is often turbid, a high WBC count (consisting predominantly of PMNs), elevated protein, and a low CSF:blood glucose ratio. A CSF glucose level of ≤ 18 mg/dL or a CSF:blood glucose ratio of < 0.23 strongly suggests bacterial meningitis. However, changes in CSF glucose may lag 30 to 120 min behind changes in blood glucose. In acute bacterial meningitis, an elevated protein level (usually 100 to 500 mg/dL) indicates blood-brain barrier injury.
CSF cell count and protein and glucose levels in patients with acute bacterial meningitis are not always typical. Atypical CSF findings may include
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Table 4
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| CSF Findings in Meningitis |
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Condition
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Predominant Cell Type*
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Protein*
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Glucose*
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Specific Tests
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Normal CSF
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All lymphocytes (0–5 cells/μL)
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< 40 mg/dL
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> 50 % of blood glucose
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None
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Bacterial meningitis
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Leukocytes (usually PMNs), often greatly increased
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Elevated
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< 50% of blood glucose (may be extremely low)
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Gram staining (yield is high if 105 colony-forming units of bacteria/ mL are present)
Bacterial culture
PCR if available
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Viral meningitis
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Lymphocytes (may be mixed; PMNs and lymphocytes during the first 24–48 h)
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Elevated
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Usually normal
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PCR (to check for enteroviruses or herpes simplex, herpes zoster, or West Nile virus)
IgM (to check for West Nile virus or other arboviruses)
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†Tuberculous meningitis
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PMNs and lymphocytes (usually pleocytosis)
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Elevated
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< 50% of blood glucose (may be extremely low)
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Acid-fast staining
PCR
Mycobacterial culture (ideally using a CSF sample of ≥ 30 mL)
Interferon-γ tests of serum and (if available) CSF
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Fungal meningitis
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Usually lymphocytes
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Elevated
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< 50% of blood glucose (may be extremely low)
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Cryptococcal antigen test
Serologic tests for Coccidioides immitis or Histoplasma sp antigen, especially if patients have recently spent time in an endemic area
Fungal culture (ideally using a CSF sample of ≥ 30 mL)
India ink (for Cryptococcus sp)
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*Changes in cell count, glucose, and protein may be minimal in severely immunocompromised patients.
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†In tuberculous meningitis, CSF acid-fast staining can be insensitive, sensitivity of PCR is only about 50%, and culture requires up to 8 wk. Positive CSF interferon-γ tests indicate tuberculous meningitis, but serum interferon-γ tests may only indicate prior infection. Thus, confirming a diagnosis of tuberculous meningitis is difficult, and if it is strongly suspected, even if not confirmed, it is treated presumptively.
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‡A small number of cells may be present normally in neonates or after a seizure.
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PCR = polymerase chain reaction; PMNs = polymorphonuclear neutrophils.
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Identification of the causative bacteria involves Gram staining, culture, and, when available, PCR. Gram staining provides information rapidly, but the information is limited. For bacteria to be reliably detected with Gram stain, about 105 bacteria/mm3 must be present. Results may be falsely negative if CSF is handled carelessly, if bacteria are not adequately resuspended after CSF has been allowed to settle, or if errors in decolorization or reading of the slide occur. Diagnosis of the specific bacteria and determination of antibiotic sensitivity requires bacterial culture. If clinicians suspect an anaerobic infection or other unusual bacteria, they should tell the laboratory before samples are plated for cultures. Prior antibiotic therapy can reduce the yield from Gram staining and culture. PCR, if available, may be a useful adjunctive test, especially in patients who have already received antibiotics.
Until the cause of meningitis is confirmed, other tests using samples of cerebrospinal fluid or blood may be done to check for other causes of meningitis, such as viruses (particularly herpes simplex), fungi, and cancer cells. Samples from other sites suspected of being infected (eg, urinary or respiratory tract) are also cultured .
Prognosis
For children < 19 yr, the mortality rate may be as low as 3% but is often higher; survivors may be deaf and neuropsychologically impaired. The mortality rate is about 17% for adults < 60 yr but up to 37% in those > 60. Community-acquired meningitis due to S. aureus has a mortality rate of 43%.
In general, mortality rate correlates with depth of obtundation or coma. Factors associated with a poor prognosis include
Seizures and a low CSF:serum glucose ratio may also indicate a poor prognosis.
Treatment
Antibiotics are the mainstay of therapy. In addition to antibiotics, treatment includes measures to decrease brain and cranial nerve inflammation and increased ICP. Most patients are admitted to an ICU.
Antibiotics:
Antibiotics must be bactericidal for the causative bacteria and must be able to penetrate the blood-brain barrier.
If patients appear ill and findings suggest meningitis, antibiotics (see Meningitis: Initial Antibiotics for Acute Bacterial Meningitis ) are started as soon as blood cultures are drawn. If lumbar puncture is delayed pending neuroimaging results, treatment begins before neuroimaging. If patients do not appear very ill or have atypical symptoms and the diagnosis is less certain, antibiotics can wait until CSF results are known.
Appropriate empiric antibiotics depend on the patient's age and immune status and route of infection (see Meningitis: Initial Antibiotics for Acute Bacterial Meningitis). In general, clinicians should use antibiotics that are effective against S. pneumoniae, N. meningitidis, and S. aureus. Sometimes (eg, in neonates and some immunosuppressed patients), herpes simplex encephalitis cannot be excluded; thus, acyclovir is added. Antibiotic therapy may need to be modified based on results of culture and sensitivity testing. Commonly used antibiotics include 3rd-generation cephalosporins for S. pneumoniae and N. meningitidis, ampicillin for L monocytogenes, and vancomycin for penicillin-resistant strains of S. pneumoniae and for S. aureus.
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Table 5
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Initial Antibiotics for Acute Bacterial Meningitis |
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Patient Group
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Suspected Bacteria
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Provisional Antibiotics
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Age
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< 3 mo
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Streptococcus agalactiae
Escherichia coli or other gram-negative bacteria
Listeria monocytogenes
Staphylococcus aureus*
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Ampicillin
Ceftriaxone or cefotaxime
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3 mo–18 yr
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Neisseria meningitidis
S. pneumoniae
S. aureus*
Haemophilus influenzae ‡
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Cefotaxime or ceftriaxone
Vancomycin
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18–50 yr
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S. pneumoniae
N. meningitidis
S. aureus*
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Ceftriaxone or cefotaxime
Vancomycin
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> 50 yr
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S. pneumoniae
L. monocytogenes
S. aureus
Gram-negative bacteria
N. meningitidis (unusual in this age group)
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Ceftriaxone or cefotaxime
Ampicillin
Vancomycin
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Route
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Sinusitis, otitis, CSF leaks
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S. pneumoniae †
H. influenzae
Gram-negative bacteria including Pseudomonas aeruginosa
Anaerobic or microaerophilic streptococci
Bacteroides fragilis
S. aureus*
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Vancomycin
Ceftazidime or meropenem
Metronidazole
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Penetrating head wounds, neurosurgical procedures, shunt infections
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S. aureus
S. epidermidis
Gram-negative bacteria including P. aeruginosa
S. pneumoniae
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Vancomycin
Ceftazidime
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Immune status
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AIDS, other conditions that impair cell-mediated immunity
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S. pneumoniae
L. monocytogenes
Gram-negative bacteria including P. aeruginosa
S. aureus*
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Ampicillin
Ceftazidime
Vancomycin
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*S. aureus is an uncommon cause of meningitis except when the route is a penetrating head wound or a neurosurgical procedure. However, it can cause meningitis in all patient groups. Thus, vancomycin or other antistaphylococcal antibiotics should be given if clinicians think that this bacteria is a possible, even if unlikely, cause.
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† S. pneumoniae is the most common causative bacteria in patients with a CSF leak or acute otitis. Such patients may be treated with vancomycin and ceftriaxone or cefotaxime. However, when meningitis is accompanied by subdural empyema or develops after a neurosurgical procedure, other bacteria, including P. aeruginosa, are more likely to be present; in such cases, initial treatment should include vancomycin plus ceftazidime plus metronidazole.
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‡
H. influenzae should be considered in children < 5 yr with no record of H. influenzae type b conjugate vaccination.
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Table 6
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Specific Antibiotics for Acute Bacterial Meningitis |
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Bacteria
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Age Group
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Antibiotics*
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Comments
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Gram-positive bacteria (unidentified)
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Children and adults
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Vancomycin
Ceftriaxone (cefotaxime) and ampicillin†
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—
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Gram-negative bacilli (unidentified)
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Children and adults
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Cefotaxime (or ceftriaxone, meropenem, or ceftazidime)
Gentamicin, tobramycin, or amikacin‡ if systemic infection is suspected
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—
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Haemophilus influenzae type b
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Children and adults
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Ceftriaxone (cefotaxime)
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—
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Neisseria meningitidis
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Children and adults
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Ceftriaxone (cefotaxime)
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Penicillin G is used for susceptible strains after sensitivities are known.
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Streptococcus pneumoniae
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Children and adults
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Vancomycin and ceftriaxone (cefotaxime)
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Penicillin G may be used for susceptible strains after sensitivities are known.
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Staphylococcus aureus and S. epidermidis
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Children and adults
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Vancomycin with or without rifampin
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Vancomycin is used for methicillin-resistant strains, or nafcillin or oxacillin may be used after sensitivities are known.
Rifampin is added if no improvement occurs with vancomycin or nafcillin.
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Listeria sp
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Children and adults
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Ampicillin (penicillin G)
Trimethoprim/sulfamethoxazole‡
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Penicillin G is used for susceptible strains after sensitivities are known.
Trimethoprim/sulfamethoxazole is used in patients who are allergic to penicillin.
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Enteric gram-negative bacteria (eg,Escherichia coli, Klebsiella sp, Proteus sp)
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Children and adults
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Ceftriaxone (cefotaxime)
Gentamicin, tobramycin, or amikacin‡ if systemic infection is suspected
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—
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Pseudomonas sp
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Children and adults
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Meropenem (ceftazidime or cefepime), usually alone but sometimes with an aminoglycoside
Aztreonam
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—
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*Alternative antibiotics are in parentheses.
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†If gram-positive bacteria are pleomorphic, ampicillin is included to cover Listeria sp.
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‡
Amikacin is used in areas where gentamicin resistance is common. Because aminoglycosides have poor CSF penetration, they are infrequently used for treatment of meningitis. When required, they may have to be given intrathecally or via an Ommaya reservoir, especially in patients with Pseudomonas meningitis. When aminoglycosides are used, renal function should be monitored.
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Corticosteroids:
Dexamethasone is used to decrease cerebral and cranial nerve inflammation and edema; it should be given when therapy is started. Adults are given 10 mg IV; children are given 0.15 mg/kg IV. Dexamethasone is given immediately before or with the initial dose of antibiotics and q 6 h for 4 days.
Other measures:
The effectiveness of other measures is less well-proved. Patients presenting with papilledema or signs of impending brain herniation are treated for increased ICP: elevation of the head of the bed to 30˚, hyperventilation to a PCO2 of 27 to 30 mm Hg to cause intracranial vasoconstriction, and osmotic diuresis with IV mannitol. Usually, adults are given mannitol 1 g/kg IV bolus over 30 min, repeated prn q 3 to 4 h or 0.25 g/kg q 2 to 3 h, and children are given 0.5 to 2.0 g/kg over 30 min, repeated prn.
Supportive measures can include IV fluids, anticonvulsants, treatment of concomitant infections, and treatment of specific complications (eg, corticosteroids for Waterhouse-Friderichsen syndrome, surgical drainage for subdural empyema).
Prevention
Use of vaccines for H. influenzae type B and, to a lesser extent, for N. meningitidis and S. pneumoniae has reduced the incidence of bacterial meningitis.
Physical measures:
Keeping patients in respiratory isolation (using droplet precautions) for the first 24 h of therapy can help prevent meningitis from spreading. Gloves, masks, and gowns are used.
Vaccination:
Vaccination can prevent certain types of bacterial meningitis.
A conjugated pneumococcal vaccine effective against 7 serotypes, including > 80% of organisms that cause meningitis, is recommended for all children (see Immunization: Pneumococcal Disease and Table 12: Approach to the Care of Normal Infants and Children: Recommended Immunization Schedule for Ages 0–6 yr).
Routine vaccination against H. influenzae type b is highly effective and begins at age 2 mo.
A quadrivalent meningococcal vaccine is given to
During an epidemic, the population at risk (eg, college students, a small town) must be identified, and its size must be determined before proceeding to mass vaccination. The effort is expensive and requires public education and support, but it saves lives and reduces morbidity.
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 prolonged face-to-face contact with a patient who has meningitis (eg, household or day care contacts, medical personnel and other people who are exposed to the patient's oral secretions) should be given postexposure chemoprophylaxis.
For meningococcal meningitis, chemoprophylaxis consists of one of the following:
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 other types of bacterial meningitis.
Key Points
Last full review/revision February 2013 by John E. Greenlee, MD
Content last modified March 2013
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