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PROFESSIONAL VERSION
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 inammation. Later, bacteria release
endotoxins, teichoic acid, and other substances that trigger an inammatory 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.
Inammation in the subarachnoid space is accompanied by cortical encephalitis and
ventriculitis. Complications are common and may include
Hydrocephalus (in some patients)
Arterial or venous infarcts due to inammation and thrombosis of arteries and veins
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Etiology
Likely causes depend on
Patient age
Route of entry
Immune status of the patient
Age
In children and young adults, the most common causes are
Neisseria meningitidis
Streptococcus pneumoniae
N. meningitidis meningitis occasionally causes death within hours. Sepsis caused by N.
meningitidis sometimes results in bilateral adrenal hemorrhagic infarction (WaterhouseFriderichsen syndrome).
Haemophilus inuenzae 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.
inuenzae vaccine is widely used. However, in areas where it is not widely used, H.
inuenzae 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
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S. pneumoniae
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.
Bacteria
Neisseria meningitidis
Children and
young adults
Streptococcus pneumoniae
S. aureus*
Haemophilus inuenzae (rare in developed countries but still seen in countries where the H.
inuenzae type B vaccine is not widely used)
S. pneumoniae
Middle-aged
adults
S. aureus*
N. meningitidis (less common in this age group)
S. pneumoniae
The elderly
S. aureus*
Listeria monocytogenes
Gram-negative bacteria
* 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.
Route
Routes of entry include the following:
By hematogenous spread (the most common route)
From infected structures in or around the head (eg, sinuses, middle ear, mastoid
process), sometimes associated with a CSF leak
Through a penetrating wound
After a neurosurgical procedure (eg, if a ventricular shunt becomes infected)
Through congenital or acquired defects in the skull or spine
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Having any of the above conditions increases the risk of acquiring meningitis.
Bacteria
Streptococcus pneumoniae
Haemophilus inuenzae
S. aureus
S. epidermidis
A neurosurgical procedure
Immune status
Overall, the most common causes in immunocompromised patients are
S. pneumoniae
L. monocytogenes
Pseudomonas aeruginosa
Mycobacterium tuberculosis
N. meningitidis
Gram-negative bacteria
But the most likely bacteria depend on the type of immune deciency:
Defects in cell-mediated immunity (eg, in AIDS, Hodgkin lymphoma, or drug-induced
immunosuppression): L. monocytogenes or mycobacteria
Defects in humoral immunity or splenectomy: S. pneumoniae or, less frequently, N.
meningitidis (both can cause fulminant meningitis)
Neutropenia: P. aeruginosa or gram-negative enteric bacteria
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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.
Diagnosis
CSF analysis
As soon as acute bacterial meningitis is suspected, blood cultures and lumbar puncture for
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CSF analysis (unless contraindicated) are done. If the patient is very ill, antibiotics are given
immediately. The need for conrmation 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 decits 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.
Lumbar puncture
Unless contraindicated, lumbar puncture see Lumbar puncture (spinal tap) is done
immediately to obtain CSF for analysis, the mainstay of diagnosis.
Contraindications to immediate lumbar puncture are signs suggesting markedly increased
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ICP or a mass; typically, these signs include focal decits, 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 ndings in bacterial meningitis include increased pressure, uid 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 ndings may include
Normal in early stages except for the presence of bacteria
Predominance of lymphocytes in about 14% of patients, particularly in neonates with
gram-negative meningitis, patients with meningitis due to L. monocytogenes, and some
patients with partially treated bacterial meningitis
Normal glucose in about 9% of patients
Normal WBC counts in severely immunosuppressed patients
Protein* Glucose*
Normal
CSF
< 40
mg/dL
Bacterial
meningitis
Specic Tests
> 50 % of
None
blood glucose
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Viral
meningitis
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Fungal
meningitis
Usually lymphocytes
*Changes in cell count, glucose, and protein may be minimal in severely immunocompromised patients.
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- tests indicate tuberculous meningitis, but serum
interferon- tests may only indicate prior infection. Thus, conrming a diagnosis of tuberculous meningitis is
dicult, and if it is strongly suspected, even if not conrmed, it is treated presumptively.
A small number of cells may be present normally in neonates or after a seizure.
Identication 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 10 5 bacteria/mm 3 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 specic 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 conrmed, other tests using samples of cerebrospinal uid
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
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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
Age > 60 yr
Coexisting debilitating disorders
A low Glasgow coma score at admission
Focal neurologic decits
A low CSF cell count
Increased CSF pressure (particularly)
Seizures and a low CSF:serum glucose ratio may also indicate a poor prognosis.
Treatment
Antibiotics
Corticosteroids to decrease cerebral inammation and edema
Antibiotics are the mainstay of therapy. In addition to antibiotics, treatment includes
measures to decrease brain and cranial nerve inammation 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.
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If patients appear ill and ndings suggest meningitis, antibiotics (see Table: 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.
Suspected Bacteria
Provisional
Antibiotics
Age
Streptococcus agalactiae
< 3 mo
3 mo18 yr
Ampicillin
plus
Ceftriaxone or
cefotaxime
S. pneumoniae
Cefotaxime or
ceftriaxone
S. aureus*
plus
Haemophilus inuenzae
Vancomycin
S. pneumoniae
Ceftriaxone or
cefotaxime
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1850 yr
N. meningitidis
plus
S. aureus*
Vancomycin
S. pneumoniae
Ceftriaxone or
cefotaxime
L. monocytogenes
> 50 yr
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S. aureus
Gram-negative bacteria
N. meningitidis (unusual in this age
group)
plus
Ampicillin
plus
Vancomycin
Route
S. pneumoniae
H. inuenzae
Vancomycin
plus
Ceftazidime or
meropenem
plus
Metronidazole
S. aureus*
S. aureus
Penetrating head wounds, neurosurgical
procedures, shunt infections
S. epidermidis
Gram-negative bacteria including P.
aeruginosa
Vancomycin
plus
Ceftazidime
S. pneumoniae
Immune status
S. pneumoniae
Ampicillin
L. monocytogenes
plus
Ceftazidime
plus
Vancomycin
* 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.
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
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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.
H. inuenzae should be considered in children < 5 yr with no record of H. inuenzae type b conjugate
vaccination.
Age
Group
Antibiotics*
Comments
Vancomycin
Gram-positive bacteria
(unidentied)
Children
plus
and
adults
Ceftriaxone (cefotaxime) and
ampicillin
Cefotaxime (or ceftriaxone,
meropenem, or ceftazidime)
Gram-negative bacilli
(unidentied)
Children
plus
and
adults
Gentamicin, tobramycin, or
Children
and
Ceftriaxone (cefotaxime)
adults
Neisseria meningitidis
Children
and
Ceftriaxone (cefotaxime)
adults
Children
Vancomycin and ceftriaxone
Streptococcus pneumoniae and
(cefotaxime)
adults
Children
Staphylococcus aureus and
Vancomycin with or without
and
S. epidermidis
rifampin
adults
Ampicillin (penicillin G)
Listeria sp
Ceftriaxone (cefotaxime)
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Enteric gram-negative
bacteria (eg, Escherichia
coli, Klebsiella sp, Proteus
sp)
Pseudomonas sp
Children plus
and
Gentamicin, tobramycin, or
adults
amikacin if systemic infection
is suspected
Meropenem (ceftazidime or
cefepime), usually alone but
Children sometimes with an
aminoglycoside
and
adults
or
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Aztreonam
*Alternative antibiotics are in parentheses.
If gram-positive bacteria are pleomorphic, ampicillin is included to cover Listeria sp.
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.
Dosage
Children > 1 mo
Adults
Ceftriaxone
50 mg/kg q 12 h
2 g q 12 h
Cefotaxime
50 mg/kg q 6 h
2 g q 46 h
Ceftazidime
50 mg/kg q 8 h
2gq8h
Cefepime
2 g q 12 h
2 g q 812 h
Ampicillin
75 mg/kg q 6 h
23 g q 4 h
Penicillin G
4 million units q 4 h
4 million units q 4 h
50 mg/kg q 6 h
2gq4h
Vancomycin
15 mg/kg q 6 h
1015 mg/kg q 8 h
Meropenem
40 mg/kg q 8 h
2gq8h
2.5 mg/kg q 8 h
2 mg/kg q 8 h
Amikacin
10 mg/kg q 8 h
7.5 mg/kg q 12 h
Rifampin
6.7 mg/kg q 8 h
600 mg q 24 h
Chloramphenicol
25 mg/kg q 6 h
1gq6h
*For neonatal dosages, see Table: Recommended Dosages of Selected Parenteral Antibiotics for Neonates.
Renal function should be monitored.
Corticosteroids
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Dexamethasone is used to decrease cerebral and cranial nerve inammation 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 P CO 2 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 uids, anticonvulsants, treatment of concomitant
infections, and treatment of specic complications (eg, corticosteroids for WaterhouseFriderichsen syndrome, surgical drainage for subdural empyema).
Prevention
Use of vaccines for H. inuenzae 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 rst 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 Pneumococcal
Vaccine and Recommended Immunization Schedule for Ages 06 yr).
Routine vaccination against H. inuenzae type b is highly effective and begins at age 2 mo.
A quadrivalent meningococcal vaccine is given to
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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:
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
For adults, a uoroquinolone (ciprooxacin or levooxacin 500 mg or ooxacin 400
mg) po for 1 dose
Chemoprophylaxis against H. inuenzae 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
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Common causes include N. meningitidis and S. pneumoniae in children and adults and
Listeria sp in infants and the elderly; S. aureus occasionally causes meningitis in people
of all ages.
Typical features may be absent or subtle in infants, alcoholics, the elderly,
immunocompromised patients, and patients who develop meningitis after a
neurosurgical procedure.
If patients have focal neurologic decits, obtundation, seizures, or papilledema
(suggesting increased ICP or a mass), lumbar puncture is deferred pending results of
neuroimaging.
Acute bacterial meningitis, unless atypical or mild, is treated as soon as possible,
before the diagnosis is conrmed.
Common empirically chosen antibiotic regimens often 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).
Routine vaccination for S. pneumoniae and N. meningitidis and chemoprophylaxis
against N. meningitidis helps prevent meningitis.
Last full review/revision February 2013 by John E. Greenlee, MD
Meningitis
Overview of Meningitis
Acute Bacterial Meningitis
Viral Meningitis
Noninfectious Meningitis
Recurrent Meningitis
Subacute and Chronic Meningitis
Overview of Meningitis
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