Bacterial Meningitis

Aka: Bacterial Meningitis, Acute Bacterial Meningitis, Meningitis

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II. Epidemiology

  1. Bacterial Meningitis represents 11 to 28% of all Meningitis cases
  2. Bacterial Meningitis Annual Incidence: 0.69 per 100,000 persons (in 2007, U.S.)
    1. Prior to Vaccination, rates were 1 to 1.5 per 100,000 persons
    2. Children: 0.2 to 3.7 cases per 100,000 in U.S.
  3. Age
    1. More common in children age <2 months (prior to first doses of Prevnar and Hib Vaccines)

III. Pathophysiology

  1. Inefficient Phagocytosis of pathogen
  2. Cerebrospinal Fluid deficient in immune factors
    1. Specific Antibody
    2. Functional complement

IV. Risk Factors: Adults

  1. Recent Otitis Media or Bacterial Sinusitis (25% of cases)
  2. Pneumonia (12% of cases)
  3. Immunocompromised state (16%)

V. Causes: Bacterial

  1. Older adults over age 60 years
    1. Streptococcus Pneumoniae
    2. Escherichia coli
    3. Klebsiella Pneumoniae
    4. Streptococcus agalactiae (Group B Streptococcus)
    5. Listeria monocytogenes (more common than in other age groups)
  2. Adults
    1. Streptococcus Pneumoniae (30-50%)
    2. Neisseria Meningitidis (10-35%)
    3. Staphylococci (5-15%)
    4. Haemophilus Influenzae (1-3%)
    5. Gram Negative Bacilli (1-10%)
    6. Streptococcus species
    7. Listeria monocytogenes (esp. immunosuppressed, pregnancy)
  3. Children or Infants
    1. Streptococcus Pneumoniae (10-20%)
    2. Neisseria Meningitidis (25-40%)
    3. Haemophilus Influenzae Type B (40-60% prior to Hib Vaccine introduction)
      1. Had caused 10,000 U.S. cases per year of Bacterial Meningitis in age 6 months to 3 years
      2. Of the 95% who survived with Antibiotics, 50% were left with permanent neurologic deficits
      3. Now rare in U.S. following 1987 Hib Vaccine introduction
  4. Neonates (highest rates among any age group, 40 cases per 100,000)
    1. Group B Streptococcus (49%)
    2. Escherichia coli (18%)
    3. Listeria monocytogenes (7%)
    4. Non-Group B Streptococcus

VI. Symptoms

  1. General
    1. Fulminant onset <24 hours (25%)
    2. Respiratory illness precedes onset by <7 days (50%)
    3. Nearly half of patients present with Bacterial Meningitis in first 24 hours (contrast with days for Aseptic Meningitis)
  2. Presentation in Adults and Older Children
    1. Classic Triad (approaches 85% in some studies)
      1. Headache (87%)
      2. Nuchal Rigidity or Stiff Neck (83%)
      3. Fever (77%)
    2. Classic triad symptoms and impaired consciousness
      1. Virtually all Bacterial Meningitis patients have one of these symptoms
      2. Two of four symptoms present in 95% of patients
    3. Other Presenting Symptoms
      1. Nausea (74%)
      2. Altered Level of Consciousness (69%)
      3. Vomiting (35%)
      4. Focal neurologic deficit (29%)
      5. Seizures (5%)
      6. Lethargy
      7. Irritability
      8. Confusion
      9. Rash (26%)
  3. Newborns and Infants
    1. Presentation <1 month is subtle (e.g. Vomiting, lethargy, irritability)
    2. Temperature Instability (Hypothermia or Fever)
      1. Fever in only 60% of Meningitis cases <1 month old
    3. NO Nuchal Rigidity
    4. Listlessness
    5. Lethargy
    6. Irritability
    7. High pitched crying
    8. Refusal to eat or poor feeding
    9. Weak sucking response
    10. Vomiting
    11. Diarrhea
    12. Respiratory distress
    13. Bulging Fontanelle (late sign in 1/3 neonates)
    14. Seizures (40%)
  4. Older adults
    1. Altered Mental Status (84%)
    2. Focal neurologic deficits (46%)
    3. Less common to have Headache (60-77%), Nuchal Rigidity (31%)

VII. Signs

  1. Meningeal Irritation (50% of adult patients)
    1. Recent studies suggest low efficacy
      1. See Meningeal Irritation for specific studies
      2. Do not rely on these signs to diagnose Meningitis
      3. Lumbar Puncture is critical if higher level of suspicion regardless of Meningeal Irritation findings
    2. Nuchal Rigidity
      1. Unreliable in under age 18 months due to neck musculature not fully developed
    3. Spinal Rigidity
    4. Tests with high Test Specificity (but poor Test Sensitivity)
      1. Kernig's Sign
        1. Hip flexed to 90 degrees, and patient unable to extend knee due to hamstring pain
      2. Brudzinski's Sign
        1. Passive neck flexion results in hip flexion
  2. Skin Rash Causes
    1. Meningococcal Meningitis (present in 65% of Meningococcal Meningitis, typically Petechiae)
    2. Haemophilus Influenzae
    3. Pneumococcal Meningitis
    4. Echovirus type 9
    5. Staphylococcus Aureus
  3. Other Neurologic Signs (more common in Pneumococcal Meningitis)
    1. Cranial Nerve Palsies
    2. Altered Level of Consciousness (69%)
    3. Focal Neurologic Signs (10-20%)
    4. Seizures (5%)
    5. Papilledema (3%)
  4. Atypical presentations (classic signs often absent in these groups)
    1. Age over 65 may present with Seizures or Hemiparesis
    2. Young children may present with lethargy, irritability or Seizures

VIII. Differential Diagnosis: General

  1. See Nuchal Rigidity
  2. See Headache Causes
  3. See Altered Level of Consciousness Causes

IX. Differential Diagnosis: CNS Process

  1. Meningitis
    1. Bacterial Meningitis (13.9%)
    2. Aseptic Meningitis
      1. Viral Meningitis (most common form of Meningitis)
        1. Enterovirus Meningitis (50.9% of all Meningitis cases in adults)
        2. Herpes Simplex Virus Meningitis (8.3% of all Meningitis cases in adults)
        3. Arbovirus Meningitis (1.1% of all Meningitis cases in adults)
      2. Parasitic Meningitis
      3. Fungal Meningitis (2.7% of all Meningitis cases)
      4. Tuberculous Meningitis
      5. Drug-Induced Meningitis (e.g. NSAIDs, trimethoprim-sulfamethoxazole)
      6. Benign Recurrent Lymphocytic Meningitis
      7. Neoplastic Meningitis
      8. Leptomeningeal Carcinomatosis
  2. Encephalitis
    1. Viral Encephalitis
    2. HSV Encephalitis
    3. NMDA Ecephalitis
    4. West Nile Virus Encephalitis
  3. Other CNS Infection
    1. See Neurologic Manifestations of HIV
    2. Intracranial Abscess
    3. Lyme Disease (Neuroborreliosis)
    4. Ehrlichiosis
    5. Neurosyphilis
  4. Rheumatologic Conditions or Vasculitis
    1. Systemic Lupus Erythematosus
    2. Neurosarcoidosis
    3. Behcet Syndrome

X. Evaluation

  1. See Oostenbrink Clinical Decision Rule for Meningitis
  2. See Nigrovic Clinical Decision Rule (Bacterial Meningitis Score, for children <19 years old)
  3. See Meningitest

XI. Diagnosis

  1. Lumbar Puncture
    1. See evaluation for LP indications (do not hesitate to obtain when clinical suspicion dictates)
    2. See Labs below
  2. Consider CT Head prior to Lumbar Puncture
    1. See Lumbar Puncture for CT Head indications (to rule out CNS Mass at risk for Brainstem Herniation)
    2. However, do not delay empiric Antibiotics while awaiting CT Head, Lumbar Puncture
    3. Obtain Blood Cultures immediately and then administer empiric Antibiotics
      1. Even before Head CT and Lumbar Puncture completed

XII. Labs

  1. CSF Exam consistent with Bacterial Meningitis (everything increased except the Glucose)
    1. Precautions
      1. CSF may be atypical despite Bacterial Meningitis in Immunocompromised, older, Listeria or partially treated cases
      2. Cell type (e.g. Pleocytosis) cannot differentiate from Aseptic Meningitis in age <18 years old
      3. Use age-adjusted cut-offs for CSF Cell Counts in infants
    2. See Nigrovic Clinical Decision Rule
    3. CSF Leukocytes
      1. Over 500 (mean 5k-20k) with >80% Neutrophils
      2. Over 50k suggests Brain Abscess
      3. May be 100 (with only 50% Neutrophils) in Listeria infection
    4. CSF Opening Pressure
      1. Exceeds 180 mm H2O
    5. CSF Protein
      1. CSF Protein >100 mg/dl (may be normal with listeria)
      2. Range: 100-500 mg/dl (typically >250 mg/dl in Bacterial Meningitis)
    6. CSF Glucose
      1. Less than 40% of Blood Glucose (or less than 40 mg/dl)
    7. CSF Gram Stain Positive
      1. Test Sensitivity 75% (untreated)
    8. CSF Culture Positive
      1. Test Sensitivity 70-80%
    9. CSF Latex Agglutination (replaced with PCR testing)
      1. Rapid test for common Bacteria (high Test Specificity, BUT poor sensitivity)
      2. Does not rule-out Bacterial Meningitis
    10. CSF Polymerase Chain Reaction (PCR)
      1. Available for Enterovirus, West Nile Virus, HSV, VZV, EBV, CMV, Tuberculosis, Neurosyphilis
  2. Blood Culture (40-60% sensitivity)
    1. Haemophilus Influenzae (uncommon now due to Vaccine)
    2. Streptococcus Pneumoniae
    3. Neisseria Meningitidis
  3. Complete Blood Count
    1. Peripheral White Blood Cell Count does not distinguish Bacterial Meningitis from Aseptic Meningitis
    2. A normal White Blood Cell Count does not rule-out Bacterial Meningitis (esp. in young children)
  4. Urine Culture
    1. Indicated in infants
  5. Other markers that may be useful in differentiating Bacterial Meningitis
    1. C-Reactive Protein
      1. High Negative Predictive Value (but not useful if positive)
      2. Gerdes (1998) Scand J Clin Lab Invest 58(5): 383-93 [PubMed]
    2. Procalcitonin
      1. Test Sensitivity 96%, Test Specificity >89% for Bacterial Meningitis
      2. Henry (2016) Clin Pediatr 55(8): 749-64 [PubMed]
      3. Vikse (2015) Int J Infect Dis 38:78-76 [PubMed]
    3. CSF Lactate
      1. Test Sensitivity >93 and Test Specificity >92% for Bacterial Meningitis
      2. Sakushima (2011) J Infect 62(4): 255-62 [PubMed]

XIII. Imaging

  1. See Lumbar Puncture for imaging indications prior to LP
  2. Head imaging indications
    1. Neurologic deficit
    2. Hypertension with Bradycardia
    3. Respiratory Failure
    4. Immunosuppression
    5. Seizure within prior week

XIV. Management

  1. See Bacterial Meningitis Management

XV. Complications

  1. Acute
    1. Increased Intracranial Pressure
      1. See Bacterial Meningitis Management
    2. Seizures (20-30% of children with Bacterial Meningitis)
      1. Evaluate for Hypoglycemia and Hyponatremia
      2. See Status Epilepticus
      3. Consider anticonvulsants for prolonged or recurrent Seizures
    3. Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
    4. Subdural Effusion (15-40% of children with Bacterial Meningitis)
      1. Risk factors include younger age, Leukopenia, higher CSF Protein
      2. Consider Subdural Empyema in clinical deterioration
  2. Chronic: Children
    1. Cognitive Impairment: 30 to 45%
    2. Hearing Loss: 6.7 to 31% reversible (2-7% permanent Deafness)
    3. Spasticity or paresis: 3.5%
    4. Seizure Disorder: 1.8 to 4.2%
    5. Mortality: 0.3 to 3.8%
  3. Chronic: adults
    1. Focal neurologic deficits: 37-50% (Hemiparesis in 4-6%)
    2. Cardiorespiratory failure: 29-38%
    3. Seizure Disorder: 15-24%
    4. Mortality: 15-21%
    5. Hearing Loss: 14-69%

XVI. Prevention

  1. Postexposure Prophylaxis
    1. See Bacterial Meningitis Postexposure Prophylaxis
    2. Indicated only in Meningococcal Meningitis and Haemophilus influenza Meningitis
      1. Not indicated in other Bacterial Meningitis exposure
  2. Primary Prevention (including Asplenic patients, HIV Infection)
    1. Meningococcal Vaccine
    2. Haemophilus InfluenzaeVaccine
    3. Adult Pneumococcal Vaccine
      1. Decreases Bacterial Meningitis risk by 50%

XVII. Prognosis

  1. Overall mortality: 15.6%
  2. Meningococcal Meningitis
    1. Meningococcemia: Prognosis poor (20-30% fatality)
    2. Meningitis alone: Better prognosis (4-5% case fatality)
  3. Pneumococcal Meningitis (highest morbidity and mortality)
    1. Case fatality rate 10% in children (30% in adults)
    2. Morbidity >30% (Hearing Loss common in children)
    3. Worse prognosis with Penicillin-resistant strains
  4. Tuberculous Meningitis
    1. Mortality rate: 19.3%
    2. Neurologic sequelae: 53.9%
    3. Chiang (2014) Lancet Infect Dis 14(10): 947-57 [PubMed]
  5. Poor prognostic factors
    1. Low Glasgow Coma Scale
    2. Systemic compromise (e.g. Tachycardia, low CSF white count, positive Blood Cultures)
    3. Abnormal Neurologic Exam
    4. Alcoholism
    5. Pneumococcal infection
    6. Male gender

XVIII. Reference

  1. Fuchs and Yamamoto (2012) APLS, Jones and Bartlett, Burlington, p. 175-80
  2. Gilbert (1998) Sanford Guide to Antimicrobial Therapy
  3. Wilson (1991) Harrison's Internal Medicine, p. 651-2
  4. Choi (2001) Clin Infect Dis 33:1380-5 [PubMed]
  5. Mount (2017) Am Fam Physician 96(5): 314-22 [PubMed]
  6. Tunkel (1997) Am Fam Physician 56(5):1355-62 [PubMed]

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