(See also Overview of Meningitis Overview of Meningitis Meningitis is inflammation of the meninges and subarachnoid space. It may result from infections, other disorders, or reactions to drugs. Severity and acuity vary. Findings typically include... read more and Neonatal Bacterial Meningitis Neonatal Bacterial Meningitis Neonatal bacterial meningitis is inflammation of the meninges due to bacterial invasion. Signs are those of sepsis, central nervous system irritation (eg, lethargy, seizures, vomiting, irritability... read more .)
Pathophysiology of Acute Bacterial Meningitis
Most commonly, bacteria reach the subarachnoid space and meninges via hematogenous spread. Bacteria may also reach the meninges from nearby infected structures or through a congenital or acquired defect in the skull or spine (see Route of entry Route of entry 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... read more ).
Because white blood cells (WBCs), immunoglobulins, and complement are normally sparse or absent from cerebrospinal fluid (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 tumor necrosis factor (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. Brain parenchyma is typically affected in acute bacterial meningitis.
Inflammation in the subarachnoid space is accompanied by cortical encephalitis and ventriculitis.
Complications of bacterial meningitis are common and may include
Hydrocephalus (in some patients)
Arterial or venous infarcts due to inflammation and thrombosis of arteries and veins in superficial and sometimes deep areas of brain
Abducens palsy Sixth Cranial (Abducens) Nerve Palsy Sixth cranial nerve palsy affects the lateral rectus muscle, impairing eye abduction. The eye may be slightly adducted when the patient looks straight ahead. The palsy may be secondary to nerve... read more due to inflammation of the 6th cranial nerve
Deafness due to inflammation of the 8th cranial nerve or structures in the middle ear
Increased intracranial pressure (ICP) due to cerebral edema
Systemic complications (which are sometimes fatal), such as septic shock Sepsis and Septic Shock Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection. In septic shock, there is critical reduction in tissue perfusion; acute failure... read more , disseminated intravascular coagulation Disseminated Intravascular Coagulation (DIC) Disseminated intravascular coagulation (DIC) involves abnormal, excessive generation of thrombin and fibrin in the circulating blood. During the process, increased platelet aggregation and coagulation... read more (DIC), or hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion Syndrome of inappropriate antidiuretic hormone secretion (SIADH) Hyponatremia is decrease in serum sodium concentration 136 mEq/L ( 136 mmol/L) caused by an excess of water relative to solute. Common causes include diuretic use, diarrhea, heart failure, liver... read more (SIADH)
Etiology of Acute Bacterial Meningitis
Likely causes of bacterial meningitis depend on
Route of entry
Immune status of the patient
In neonates Neonatal Bacterial Meningitis Neonatal bacterial meningitis is inflammation of the meninges due to bacterial invasion. Signs are those of sepsis, central nervous system irritation (eg, lethargy, seizures, vomiting, irritability... read more and young infants, the most common causes of bacterial meningitis are
Group B streptococci, particularly Streptococcus agalactiae
Escherichia (E.) coli and other gram-negative bacteria
In older infants, children, and young adults, the most common causes of bacterial meningitis are
N. meningitidis meningitis occasionally causes death within hours. Sepsis caused by N. meningitidis sometimes results in coagulopathy and bilateral adrenal hemorrhagic infarction (Waterhouse-Friderichsen syndrome).
Haemophilus influenzae type B, previously the most common cause of meningitis in children < 6 years 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 the vaccine is not widely used, H. influenzae is still a common cause, particularly in children aged 2 months to 6 years.
In middle-aged and in older adults, the most common cause of bacterial 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.
In people of all ages, Staphylococcus aureus occasionally causes meningitis.
Route of entry
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 head wound
After a neurosurgical procedure (eg, if a ventricular shunt becomes infected)
Through congenital or acquired defects in the skull or spine
Having any of the above conditions increases the risk of acquiring meningitis.
Overall, the most common causes of bacterial meningitis in immunocompromised patients are
But the most likely bacteria depend on the type of immune deficiency:
Defects in cell-mediated immunity Cellular immunity deficiencies Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more (eg, in AIDS, Hodgkin lymphoma, or drug-induced immunosuppression): L. monocytogenes or mycobacteria
Defects in humoral immunity Humoral immunity deficiencies Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more or splenectomy: S. pneumoniae or, less frequently, N. meningitidis (both can cause fulminant meningitis)
In very young infants (particularly premature infants) and older adults, T-cell immunity may be weak; thus, these age groups are at risk of meningitis due to L. monocytogenes.
Symptoms and Signs of Acute Bacterial Meningitis
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 symptoms and signs of meningitis include
Changes in mental status (eg, lethargy, obtundation)
Nuchal rigidity (although not all patients report it)
Back pain (less intense than and overshadowed by headache)
However, fever, headache, and nuchal rigidity may be absent in neonates and infants (see Neonatal Bacterial Meningitis Symptoms and Signs Neonatal bacterial meningitis is inflammation of the meninges due to bacterial invasion. Signs are those of sepsis, central nervous system irritation (eg, lethargy, seizures, vomiting, irritability... read more ). So-called paradoxical irritability, in which cuddling and consoling by a parent irritates rather than comforts the neonate, suggests bacterial meningitis.
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 increases intracranial pressure (ICP) and typically causes papilledema Papilledema Papilledema is swelling of the optic disk due to increased intracranial pressure. Optic disk swelling resulting from causes that do not involve increased intracranial pressure (eg, malignant... read more , but papilledema may be absent early or be attenuated because of age-related or other factors.
Accompanying systemic infection by the organism may cause
Rashes, petechiae, or purpura (which suggest meningococcemia)
Pulmonary consolidation (often in meningitis due to S. pneumoniae)
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 older patients and in alcoholics. Often, in older patients, the only sign is confusion in those who were previously alert or altered responsiveness in those who have dementia. In such patients, as in neonates, the threshold for doing lumbar puncture should be low. Brain imaging (MRI or, less optimally, CT) should be done if focal neurologic deficits are present or increased ICP is suspected.
If bacterial meningitis develops after a neurosurgical procedure, symptoms often take days to develop.
Diagnosis of Acute Bacterial Meningitis
Cerebrospinal fluid (CSF) analysis
As soon as acute bacterial meningitis is suspected, blood cultures and lumbar puncture for CSF analysis (unless contraindicated) are done. Blood should be analysed when lumbar puncture is done so that blood glucose levels can be compared with CSF glucose levels. Treatment should be started as follows:
If bacterial meningitis is suspected and the patient is very ill, antibiotics and corticosteroids are given immediately, even before lumbar puncture.
If bacterial meningitis is suspected and lumbar puncture will be delayed pending CT or MRI, antibiotics and corticosteroids should be started after blood cultures but before neuroimaging is done; 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 older patients, alcoholics, and immunocompromised patients. Diagnosis can be challenging in the following patients:
Those who have had a neurosurgical procedure because such procedures can also cause changes in mental status and neck stiffness
Older patients and alcoholics because changes in mental status may be due to metabolic encephalopathy (which may have multiple causes) or to falls and subdural hematomas
Focal seizures or focal neurologic deficits may indicate a focal lesion such as a brain abscess Brain Abscess A brain abscess is an intracerebral collection of pus. Symptoms may include headache, lethargy, fever, and focal neurologic deficits. Diagnosis is by contrast-enhanced MRI or CT. Treatment is... read more .
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, older patients, alcoholics, immunocompromised patients, and patients who had neurosurgical procedure because symptoms may be atypical.
Pearls & Pitfalls
If findings suggest acute bacterial meningitis, routine tests include
Complete blood count and differential
Blood cultures plus polymerase chain reaction (PCR), if available
Unless contraindicated, lumbar puncture Lumbar Puncture (Spinal Tap) Lumbar puncture is used to do the following: Evaluate intracranial pressure and cerebrospinal fluid (CSF) composition (see table Cerebrospinal Fluid Abnormalities in Various Disorders) Therapeutically... read more is done immediately to obtain CSF for analysis, the mainstay of diagnosis.
Contraindications to immediate lumbar puncture are signs suggesting markedly increased ICP or an intracranial mass effect (eg, due to edema, hemorrhage, or tumor); typically, these signs include
Focal neurologic deficits
Deterioration in consciousness
Seizures (within 1 week of presentation)
History of central nervous system disease (eg, mass lesion, stroke, focal infection)
In such cases, lumbar puncture may cause brain herniation and thus is deferred until neuroimaging (typically CT or MRI) is done to check for increased ICP or a mass effect. 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 effect or obstructive hydrocephalus is detected, lumbar puncture can be done.
CSF should be sent for analysis: cell count, protein, glucose, Gram staining, culture, PCR, and other tests as indicated clinically. A new multiplex film-array PCR panel can provide rapid screening for multiple bacteria and viruses plus Cryptococcus neoformans in a CSF sample. This test, which is not always available, is used to supplement, not replace, culture and traditional tests. 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 white blood cells (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 the following (see table CSF Findings in Meningitis ):
Fluid that is often turbid
A high WBC count (consisting predominantly of polymorphonuclear neutrophils)
A low CSF:blood glucose ratio
A CSF:blood glucose level of < 50% suggests possible meningitis. 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 minutes 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
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
When initial CSF findings are equivocal, a repeat lumbar puncture 12 to 24 hours later can sometimes clarify which direction CSF changes are heading or whether there was a laboratory error.
Identification of the causative bacteria in CSF 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/mL must be present. Results may be falsely negative if any of the following occur:
CSF is handled carelessly.
Bacteria are not adequately resuspended after CSF has been allowed to settle.
Errors in decolorization or reading of the slide occur.
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, and latex agglutination tests to detect bacterial antigens may be a useful adjunctive tests, especially in patients who have already received antibiotics.
Determination of antibiotic sensitivity requires bacterial culture.
Until the cause of meningitis is confirmed, other tests using samples of CSF 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) should also be cultured.
Prognosis for Acute Bacterial Meningitis
With antibiotic treatment, the mortality rate for children < 19 years may be as low as 3% but is often higher; survivors may be deaf and neuropsychologically impaired. The mortality rate, even with antibiotic treatment, is about 17% for adults < 60 years 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 years
Coexisting debilitating disorders
A low Glasgow coma score at admission (see tables Glasgow Coma Scale Glasgow Coma Scale and Modified Glasgow Coma Scale Modified Glasgow Coma Scale for Infants and Children )
Focal neurologic deficits
A low CSF cell count
Increased CSF pressure (particularly)
Seizures and a low CSF:serum glucose ratio may also indicate a poor prognosis.
Treatment of Acute Bacterial Meningitis
Corticosteroids to decrease cerebral inflammation and edema
Antibiotics are the mainstay of therapy for acute bacterial meningitis. In addition to antibiotics, treatment includes measures to decrease brain and cranial nerve inflammation and increased intracranial pressure (ICP).
Most patients are admitted to an intensive care unit (ICU).
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 table Initial Antibiotics for Acute Bacterial Meningitis Initial Antibiotics for Acute Bacterial Meningitis ) and corticosteroids are started as soon as blood cultures are drawn and even before lumbar puncture. Also, if lumbar puncture is delayed pending neuroimaging results, antibiotic and corticosteroid treatment begins before neuroimaging.
Pearls & Pitfalls
Appropriate empiric antibiotics depend on the patient's age and immune status and route of infection (see table Initial Antibiotics for Acute Bacterial Meningitis Initial Antibiotics for Acute Bacterial Meningitis ). In general, clinicians should use antibiotics that are effective against S. pneumoniae, N. meningitidis, and S. aureus. In pregnant women, neonates, older patients, and immunocompromised patients, Listeria meningitis is possible; it requires specific antibiotic treatment, usually ampicillin. Herpes simplex encephalitis can clinically mimic early bacterial meningitis; 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
Vancomycin for penicillin-resistant strains of S. pneumoniae and for S. aureus
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 every 6 hours for 4 days.
Use of dexamethasone is best-established for patients with pneumococcal meningitis.
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
Osmotic diuresis with IV mannitol
Usually, adults are given mannitol 1 g/kg IV bolus over 30 minutes, repeated as needed every 3 to 4 hours or 0.25 g/kg every 2 to 3 hours, and children are given 0.5 to 2.0 g/kg over 30 minutes, repeated as needed.
Additional measures can include
Treatment of concomitant infections
Treatment of specific complications (eg, corticosteroids for Waterhouse-Friderichsen syndrome, surgical drainage for subdural empyema)
Prevention of Acute Bacterial Meningitis
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.
Keeping patients in respiratory isolation (using droplet precautions) for the first 24 hours of therapy can help prevent meningitis from spreading. Gloves, masks, and gowns are used.
Vaccination can prevent certain types of bacterial meningitis.
A conjugated pneumococcal vaccine Pneumococcal Vaccine Pneumococcal disease (eg, otitis media, pneumonia, sepsis, meningitis) is caused by some of the > 90 serotypes of Streptococcus pneumoniae (pneumococci). Vaccines are directed against... read more effective against 13 serotypes, including > 80% of organisms that cause meningitis, is recommended for all children (see table Recommended Immunization Schedule for Ages 0–6 Years Recommended Immunization Schedule for Ages 0–6 Years ).
Routine vaccination against H. influenzae type b Haemophilus influenzae Type b (Hib) Vaccine Haemophilus influenzae type b (Hib) vaccines help prevent Haemophilus infections but not infections caused by other strains of H. influenzae bacteria. H. influenzae causes... read more is highly effective and begins at age 2 months.
A quadrivalent meningococcal vaccine Meningococcal Vaccine The meningococcal serogroups that most often cause meningococcal disease in the US are serogroups B, C, and Y. Serogroups A and W cause disease outside the US. Current vaccines are directed... read more is given to
Children who are 2 to 10 years if they have an immunodeficiency or functional asplenia
All children at age 11 to 12 years with a booster dose at age 16
Older children, college students living in dormitories, and military recruits who have not had the vaccine previously
Travelers to or residents of endemic areas
Laboratory personnel who routinely handle meningococcal specimens
During a meningitis 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.
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 month, 10 mg/kg; for children < 1 month, 5 mg/kg) orally every 12 hours for 4 doses
Ceftriaxone 250 mg (for children < 15 years, 125 mg) IM for 1 dose
For adults, a fluoroquinolone (ciprofloxacin or levofloxacin 500 mg or ofloxacin 400 mg) orally for 1 dose
For meningitis due to H. influenzae type b, chemoprophylaxis is rifampin 20 mg/kg orally once a day (maximum: 600 mg/day) for 4 days. There is no consensus on whether children < 2 years require prophylaxis for exposure at day care.
Chemoprophylaxis is not usually needed for contacts of patients with other types of bacterial meningitis.
Common causes of acute bacterial meningitis include N. meningitidis and S. pneumoniae in children and adults and Listeria species in infants and older adults; S. aureus occasionally causes meningitis in people of all ages.
Typical features may be absent or subtle in infants, alcoholics, older patients, immunocompromised patients, and patients who develop meningitis after a neurosurgical procedure.
If patients have focal neurologic deficits, obtundation, seizures, or papilledema (suggesting increased ICP or an intracranial mass effect), defer lumbar puncture pending results of neuroimaging.
Treat acute bacterial meningitis as soon as possible, even before the diagnosis is confirmed.
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 H. influenza, S. pneumoniae, and N. meningitidis and chemoprophylaxis against N. meningitidis help prevent meningitis.
The following are some English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
Practice Guidelines for the Management of Bacterial Meningitis: This article reviews the recommendations for the diagnosis and management of bacterial meningitis, including the initial approach, indications for CT before lumbar puncture, tests to distinguish viral from bacterial meningitis, specific tests to identify the causative bacteria, timing of antimicrobial drugs for suspected meningitis, specific drugs to be used to treat suspected or confirmed bacterial meningitis, and the role of dexamethasone.
2017 Infectious Diseases Society of America’s Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis: This article reviews the literature, evaluates the evidence, and presents recommendations. It specifically discusses the approach to infections associated with cerebrospinal fluid shunts, cerebrospinal fluid drains, intrathecal drugs (eg, baclofen), deep brain stimulation hardware, neurosurgery, and head trauma.
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