ACUTE BACTERIAL

MENINGITIS
Major clinical syndromes
• Bacterial meningitis
• Acute (< 24 hours)
• Subacute (< 7 days)
• Chronic (> 4 weeks)
• Meningoencephalitis
• Brain abscess
• Subdural empyema
• Epidural abscess
• Septic venous sinus thrombophlebitis
Definition
• An acute purulent infection of the central nervous system (CNS),
predominantly involving the subarachnoid space, caused by bacteria.
• Associated with a CNS inflammatory reaction that may result in
• Decreased consciousness
• Seizures
• Increased intracranial pressure (ICP)
• Stroke
• Meninges, subarachnoid space, and brain parenchyma may all become
involved in the inflammatory reaction (meningoencephalitis)
Etiology
• Etiology differs by age.
• Immunosuppressed persons can have a variety of etiologic organisms,
regardless of age.
• Most common cause bacterial meningitis in adults
• S. pneumoniae
• N. meningitidis
• Most common cause bacterial meningitis in elderly persons
• S. pneumoniae
• Enteric gram-negative bacilli
• L. monocytogenes
Epidemiology
• Incidence/prevalence
• Most common form of suppurative CNS infection
• Organisms most commonly responsible for community-acquired
bacterial meningitis
• Streptococcus pneumoniae (~50%)
• N. meningitidis (~25%)
• Group B streptococci (~15%)
• Listeria monocytogenes (~10%)
• H. influenzae now accounts for < 10% of cases
• Age
• Can occur at any age, but causative organism varies according to age
• S. pneumoniae
• Most common cause of meningitis in adults > 20 years
• N. meningitidis
• Accounts for up to 60% of cases in persons 2–20 years of age
• Group B streptococcus or Streptococcus agalactiae
• Neonates, adults > 50 years, especially with underlying diseases
• L. monocytogenes
• Neonates, patients > 60 years, immunosuppressed persons
• Transmission
• Person to person by respiratory droplets, and hematogenous spread to
the CNS
• Direct/contiguous spread from adjacent focus
• Retrograde spread along nerves
• Nasopharyngeal colonization/carrier state
• Herd immunity
• Epidemic meningococcal disease in African Meningitis Belt
• Epidemics occur every 5- 10 years
• Very large epidemics with high attack rates
• Epidemics occur in dry season and decrease in the rainy season
• Peak age group 5-14 years
• Epidemics caused by serogroup A, less frequently serogroup C
(Serogroup W135 caused epidemic in 2002 in Burkina Faso)
Symptoms & Signs
• Classic clinical triad may be absent, especially in immunosuppressed
persons.
• Fever
• Headache
• Nuchal rigidity
• Alteration in mental status (>75%)
• Varies from lethargy to coma
• Nausea
• Vomiting
• Photophobia
• Seizures (20–40%)
• Initially or during course of illness
• Focal seizures
• Usually due to focal arterial ischemia or infarction, cortical venous
thrombosis with hemorrhage, or focal edema
• Generalized seizures and status epilepticus
• May be due to hyponatremia; cerebral anoxia; or, less commonly,
toxic effects of antimicrobial agents (e.g., high-dose penicillin)
• Signs of increased ICP
• Deteriorating or reduced level of consciousness
• Papilledema
• Dilated, poorly reactive pupils
• Sixth-nerve palsies
• Decerebrate posturing
• Cushing reflex (bradycardia, hypertension, and irregular respirations)
• Evidence of meningeal irritation
• Kernig’s sign
• Supine position: thigh is flexed on abdomen, with the knee flexed;
attempts to passively extend the knee elicit pain
• Brudzinski’s sign
• Supine position: passive flexion of neck causes spontaneous flexion
of hips and knees
• Jolt accentuation of headache – more sensitive maneuver
• A positive test consists of accentuation of headache by horizontal
rotation of the head at a frequency of two to three times per second
• Petechial or purpuric skin lesions (N. meningitidis)
• Begin as diffuse maculopapular rash resembling a viral exanthem
• Rapidly become petechial on trunk and lower extremities, mucous
membranes and conjunctiva, and occasionally on palms and soles
Differential Diagnosis
• Viral meningoencephalitis, particularly HSV encephalitis
• Typically present with headache, fever, altered consciousness, focal
neurologic deficits, and focal or generalized seizures
• CSF studies, neuroimaging, and electroencephalography distinguish
HSV encephalitis from bacterial meningitis.
• Typical CSF profile
• Viral CNS infections:
• Lymphocytic pleocytosis with a normal glucose concentration
• Bacterial CNS infections:
• Polymorphonuclear pleocytosis and hypoglycorrhachia
• Subacutely evolving meningitis – principal causes
• Mycobacterium tuberculosis
• Cryptococcus neoformans
• Histoplasma capsulatum
• Coccidioides immitis
• Treponema pallidum
• Subarachnoid hemorrhage
• Cervical spine disease in older persons
• May result in false-positive tests for nuchal rigidity
• Focal suppurative CNS infections, including subdural and epidural
empyema and brain abscess
• Prompt MRI in suspected meningitis if focal features present
• To detect intracranial infection
• To search for associated areas of infection in sinuses or mastoid
bones
• Chemical meningitis
• Due to rupture of tumor contents into the CSF (e.g., from a cystic
glioma, craniopharyngioma, epidermoid or dermoid cyst)
• Others
• Drug-induced hypersensitivity meningitis
• Carcinomatous or lymphomatous meningitis
• Meningitis associated with inflammatory disorders
• Sarcoid
• Systemic lupus erythematosus
• Behçet’s disease
• Pituitary apoplexy
• Uveomeningitic syndromes (Vogt-Koyanagi-Harada syndrome)
• Acute disseminated encephalomyelitis
Diagnostic Approach
• Bacterial meningitis is diagnosed by examination of the CSF.
• Blood cultures should be immediately obtained and empirical
antimicrobial therapy initiated without delay.
• May in some cases have higher sensitivity for identifying organism than
cultures of the CSF
• Antimicrobial agents should be started before lumbar puncture (and
imaging) and will not alter the CSF profile for 2–6 hours.
Laboratory Tests
• CSF abnormalities
• Elevated opening pressure
• >180 mmH2O: >90% of patients
• >400 mmH2O: 20%
• Leukocyte count – 10/μL to 10,000/μL; neutrophils predominate
• Glucose level – low, often < 2.2 mmol/L (< 40 mg/dL)
• CSF/serum glucose ratio – < 0.4 in ~60%
• Protein level – > 0.45 g/L (> 45 mg/dL) in 90%
• Gram stain – positive in > 60%
• Cultures – positive in > 80%
• Latex agglutination
• May be positive in patients with meningitis due to S. pneumoniae, N.
meningitidis, H. influenzae type b, E. coli, group B streptococci
• Specificity
• 95–100% for S. pneumoniae and N. meningitidis
• Sensitivity
• 70–100% for detection of S. pneumoniae
• 33–70% for detection of N. meningitidis
• Negative test does not exclude infection by these organisms
• Limulus amebocyte lysate
• Positive in cases of gram-negative meningitis
• Specificity of 85–100%
• Sensitivity approaching 100%
• False-positive results may occur
• PCR
• Detects bacterial DNA
• A broad-range PCR can detect small numbers of viable and nonviable
organisms in CSF and is expected to be useful for making a diagnosis of
bacterial meningitis in patients:
• Who have been pretreated with oral or parenteral antibiotics
• In whom Gram’s stain and CSF culture are negative
Imaging
• CT or MRI
• MRI – preferred for superiority in demonstrating areas of cerebral
edema and ischemia
• Obtain CT or MRI before lumbar puncture in the following cases.
• Recent head trauma
• Immunocompromised patient
• Known malignant lesions or CNS neoplasms
• Focal neurologic findings, including papilledema or a reduced level
of consciousness
• Age > 60 years
Diagnostic Procedures
• Lumbar puncture for CSF analysis
• Safe to perform without prior neuroimaging studies in
immunocompetent patients age < 60 with normal level of
consciousness and no known history or sign of: 
• Recent head trauma
• Papilledema
• Focal neurologic deficits
• Skin biopsy
• Petechial skin lesions, if present, should be sampled to reveal organism
on Gram stain (N. meningitidis).
• Contraindications to LP
• Absolute • Relative
• Skin infection over site • Increased ICP without
• Papilledema papilledema
• Focal neurological signs • Suspicion of mass lesion
• ↓MS • Spinal cord tumor
• Spinal epidural abscess
• Bleeding diathesis or low
platlets
Treatment Approach
• Bacterial meningitis is a medical emergency.
• Goal
• Begin antibiotic therapy within 60 minutes of a patient’s arrival in the
emergency department.
• Begin antibiotic therapy before CSF Gram stain and culture results are
known.
• The selected agents should have rapid penetration into the CSF.
• Therapy is then modified on the basis of results of CSF culture.
• Increased ICP should be managed emergently.
Specific Treatments
• Empirical antimicrobial therapy
• Empirical therapy of community-acquired suspected bacterial
meningitis in children and adults should include a combination of:
• Dexamethasone
• Third-generation cephalosporin (e.g., ceftriaxone or cefotaxime)
• Vancomycin
• Ampicillin should be added to the empirical regimen for coverage of L.
monocytogenes in:
• Individuals < 3 months of age
• Those >55
• Those with suspected impaired cell-mediated immunity
• Chronic illness
• Organ transplantation
• Pregnancy
• Malignancy
• Immunosuppressive therapy
• In hospital-acquired meningitis, and particularly meningitis following
neurosurgical procedures
• Empirical therapy should include a combination of vancomycin and
ceftazidime, cefepime, or meropenem.
Adjunctive therapy
• Increased ICP
• Emergency treatment includes
• Elevation of patient’s head to 30° to 45°
• Intubation
• Hyperventilation (arterial partial pressure of carbon dioxide 25–30
mmHg)
• Mannitol administration
• Monitor in intensive care unit.
• Dexamethasone
• Decreases meningeal inflammation, neurologic sequelae, and other
unfavorable outcomes, especially in patients with pneumococcal
meningitis
• Dose: 10 mg IV, 15–20 minutes before (or not later than concurrent
with) the first dose of an antimicrobial agent and repeated at same
dose every 6 hours for 4 days
• Unlikely to be of significant benefit if started > 6 hours after
antimicrobial therapy has been initiated
Monitoring
• General
• In-hospital monitoring is required for all cases.
• Monitor for complications.
• Monitor for response to therapy.
• Pneumococcal meningitis
• Repeat lumbar puncture 24–36 hours after initiation of therapy to document
sterilization of CSF.
• Increased ICP
• Monitor in intensive care unit.
• ICP monitoring device for accurate measurement and possibly drainage of CSF
Complications
• Increased ICP
• Major cause of obtundation and coma, and if untreated can lead to
herniation syndromes and death
• Cerebral herniation
• Most disastrous complication of increased ICP
• 1–8% of cases
• Seizures: focal or generalized
• Affect one-third of patients
• Subdural fluid collections
• Present in one-third of patients
• More commonly associated with H. influenzae and S. pneumoniae
• Shock
• Especially in meningococcal meningitis
• Disseminated intravascular coagulation
• Especially in meningococcal meningitis
• Cerebral ischemia or infarction
• Caused by vasculitis or infiltration of arterial wall by inflammatory cells,
with intimal thickening or venous infarction from clogging of draining
veins
• Hydrocephalus
• Dural sinus or cortical vein thrombosis
• Brain abscesses
• Brain hemorrhage
• Common sequelae (chronic complications)
• Decreased intellectual function
• Memory impairment
• Seizures
• Hearing loss
• Dizziness
• Gait disturbances
Prognosis
• Mortality rate (despite antibiotic therapy)
• 3–7% for meningitis caused by H. influenzae, N. meningitidis, or group B
streptococci
• 15% for L. monocytogenes
• 20% for S. pneumoniae
• Moderate or severe sequelae occur in ~25% of survivors; exact
incidence varies with infecting organism.
• Poor prognostic factors (increased risk of death)
• Decreased level of consciousness on admission
• Onset of seizures within 24 hours of admission
• Signs of increased ICP
• Young age (infancy) and age > 50 years
• Presence of comorbid conditions, including shock, and/or need for
mechanical ventilation
• Delay in initiation of treatment
• Decreased CSF glucose concentration (< 2.2 mmol/L [< 40 mg/dL])
• Markedly elevated CSF protein concentration (>3 g/L [>300 mg/dL])