Bacterial Meningitis

Introduction

Meningitis refers to inflammation of the leptomeninges (the tissues that surround the brain and spinal cord).  The arachnoid mater and CSF become inflamed in both the subarachnoid spance and the cerebral ventricles.

Suspected bacterial meningitis is a medical emergency!  Immediate diagnostic steps must be taken to establish the specific cause, as morbidity and mortality can be significant.  If untreated, the mortality rate of bacterial meningitis nears 100%. 

Epidemiology  

  • In the United States, the overall incidence of bacterial meningitis is between 2 and 10 cases per 100,000 people. 
  • In pediatrics, the peak incidence occurs in children less than one year old. 
  • After the introduction of the haemophilis influenzae type B and pneumococcal vaccines in the 1990s, the incidence of bacterial meningitis has declined in all age groups except children less than two months old. Neisseria meningitidis is now the most common cause of bacterial meningitis in the U.S., particularly in infants less than 1 year of age. 

Risk Factors

  • Recent infection, including respiratory or otic infection
  • Recent exposure to someone with meningococcal or HiB meningitis OR recent travel to an area with endemic meningococcal disease, such as Sub-Saharan Africa
  • Communicating anatomical defects with CNS (CSF leak)
  • Penetrating head trauma or history of ENT/neurosurgical procedure (including cochlear implants and VP shunt)
  • Immunodeficiencies (HIV, asplenia, sickle cell, complement deficiency, IgG deficiency, and preterm infants)
  • Lack of immunization against H. influenzae and S. pneumoniae

Pathogenesis

  1. Bacteria attach to and colonize the nasalpharyngeal mucosal epithelium.
  2. Bacteria invade the adjacent intravascular spaces (bloodstream).
  3. The bloodstream transports bacteria to the CSF.
  4. Bacteria survive and replicate in the CSF.
  5. An immune response is initiated by the host, with resultant migration of neutrophils. 
  6. The end result is cerebral edema, decreased arterial flow to the brain, vasculitis and thrombosis of blood vessels, and resultant ischemia.

Common Pathogens

  • While any etiologic agent can cause meningitis in any age group, some typical patterns do exist.  It is important to consider possible routes of aquisition as well as underlying host factors when attempting to determine the causative organism. 
  • Neonate: Group B strep (early onset), E. coli, listeria monocytogenes, gram negative enterics
  • One to three months of age: Group B Strep (late onset), s.pneumoniae, n.meningitidis, gram negative bacilli, listeria and Hib (rare), salmonella
  • Three months to three years of age: s.pneumoniae, n.meningitidis, h.influenzae (rare due to immunity)
  • Three to 12 years of age: s.pneumoniae, n.meningitidis, h.influenzae (rare due to immunity)
  • 12 years to adult: n.meningitidis, s.pneumoniae 

Clinical Presentation

  • Bacterial meningitis often presents acutely, with manifestations of sepsis and meningitis developing rapidly over the course of less than 24 hours. Less commonly, bacterial meningitis may develop progressively over the course of a few days, often following a febrile illness. 
  • The symptoms and signs depend on the age of the patient and the extent of the illness. 
  • Infants may have nonspecific signs and symptoms, including: fever, irritability, lethargy, poor feeding, abnormal tone, hypothermia, bulging fontanel, seizures, vomiting, respiratory distress, restlessness, and jaundice. 
  • Older children may have fever, headache, vomiting, neck stiffness, photophobia, confusion, lethargy, petechial/purpuric rash, and irritability.  Few children have the classic triad of fever, neck stiffness, and change in mental status. 
  • Meningeal signs:
    - Nuchal rigidity: inability to touch chin to chest, limited passive neck flexion
    - Kernig sign: present if supine patient with hip and knee flexed to 90 degrees cannot extend knee more than 135 degrees without back/neck pain)
    - Brudzinski sign: present if supine patient flexes hips with passive neck flexion
  • Neurologic signs:
    - Change in mental status: may be irritable, lethargic, somnolent, or comatose
    - Increased ICP: may manifest as headache, bulging fontanel or increasing head circumference, papilledema, or cranial nerve palsies
    - Seizures
    - Focal neurologic findings: may manifest as cranial nerve palsies, visual field defects, hemiparesis

Diagnosis

  1. Suspected bacterial meningitis is a medical emergency. Immediate steps must be taken to determine the specific cause. Ideally, the history, physical exam, blood tests, and lumbar puncture will be completed prior to the start of therapy. However, in the case of suspected fulminant meningitis, empiric antibiotic therapy may be started prior to the LP. 
  2. Key aspects of history: course of illness, neck stiffness, rash, seizures, vaccination history, recent illnesses, ENT/neurosurgical procedures, sick contacts, recent travel, recent antibiotic use (may impact blood cultures), allergies
  3. Complete physical exam, with emphasis on vital signs, neurologic exam and signs of increasing ICP
  4. Laboratory Evaluation: 
    -CBC with differential, CMP, blood cultures X2 (prior to start of antibiotic therapy)
    -Lumbar puncture with cell count and differential, glucose, protein, gram stain, and culture (Tube #1: Culture and gram stain, Tube #2: Glucose and Protein, Tube #3: Cell count, Tube #4: Hold for  other tests as indicated)
    -Typical CSF findings in bacterial meningitis: WBC count >1000 with predominance of neutrophils; high protein (ranges from 100-500 mg/dL), low glucose (often <40 mg/dL), high opening pressure (often 20-75 cm water), positive gram stain
    Other tests to consider:
    -Consider UA and urine culture in infants <12 months old and immunocompromised patients, as UTI may be the primary source of infection  
  5. The Role of Imaging:
    -It is not uncommon for an LP to be delayed because of concern about herniation. It should be noted that heriation is unlikely in patients without focal neurologic findings or coma, and that a normal CT does not entirely exclude the possibility of herniation. 
    -Indications for imaging with CT prior to LP include: coma, the presence of a CSF shunt, history of hydrocephalus, recent history of CNS trauma or neurosurgery, papilledema, focal neurologic deficit
    -It is usually safe to perform an LP on an infant with a bulging fontanel as long as they do not have any focal neurologic signs
     

Treatment

  1. Empiric antibiotic therapy should begin after the LP. If the LP is delayed because of concern about need for imaging, start empiric antibiotics immediately after drawing blood cultures. 
    -Neonates: ampicillin and gentomycin 
    -Infants to 18 years: third generation cephalsporin (ceftriaxone or cefotaxime) and vancomycin (provides coverage for S. pneumonia resistant to penicillin and cephalasporins)
    -Adjust antibiotics depending on results of culture and sensitivities
    -Duration of antibiotic treatment is dependent on organism
  2. Treatment with dexamthasone with first dose of antibiotic treatment is controversial

How to Follow Patients with Meningitis

  • Frequent physical examinations:
    -Evaluate mental status, with attention towards signs of increased ICP: blood pressure, pulse, eye movements, fundoscopic exam for papilledema, head circumference, breathing pattern
    -Hydration status: evaluate for signs of dehydration secondary to poor intake or vomiting. There may be fluid retention secondary to inappropriate secretion of ADH. Pay close attention to electrolytes, weight, ins and outs, and signs of edema. 
  • Fever may persist for 7 days or longer. May need to check for other sites of infections including bone, joints, urinary tract, and pneumonia.
  • Assess exposure risk for close contacts. Encourage prophylaxis as needed. 

Complications

  • Untreated bacterial meningitis is fatal in nearly 100% of cases. Even with treatment, it is estimated that up to 25% of bacterial meningitis survivors in the U.S. have moderate to severe sequelae. 
  • Patients who recieve appropriate treatment and recover may still experience significant morbidity: 
    -Intellectual deficits (ADHD, low IQ, MR, cognitive impairment, behavioral issues)
    -Hearing deficits
    -Vision deficits, including cortical blindness
    -Neurologic deficits (seizures, motor deficits, cerebral palsy)

Prevention

  • Appropriate vaccinations: pneumococcal, Hib and meningococcal vaccines.
  • Close contact chemoprophylaxis: close contacts include household contacts, day care and preschool contacts, and anyone who slept or ate in the same dwelling as the index patient during the 7 days prior to the index case's symptoms. It can be difficult to determine what a "close contact" is-- one oft-quoted rule is people who have had prolonged (more than 8 hours) of close proximity (within 3 feet) contact with the patient OR people who have had direct contact with the index patient's oral secretions. 
  • Rifampin is the drug used for prophylaxis in children, while adults may take rifampin, ciprofloxacin, or ceftriaxone. Ideally, chemoprophylaxis is started within 24 hours of diagnosis of the index case. 

References

  1. Brouwer MC, Thwaites GE, Tunkel AR, van de Beek D. Dilemmas in the Diagnosis of Acute Community-Acquired Bacterial Meningitis. The Lancet. 2012;380:1684. 
  2. Chandran A, Herbert H, Misurski D, Santosham M. Long-Term Sequelae of Childhood Bacterial Meningitis. The Pediatric Infectious Disease Journal. 2011;30:1. 
  3. Willoughby R. and Polack F. Meningitis: What's New in Diagnosis and Management. Contemporary Pediatrics. September 1998.
  4. Wubbell L and McCracken G. Management of Bacterial Meningitis. Pediatrics in Review. 1998;19:78. 
  5. Negrini B, Kelleher K, and Wald E. Cerebrospinal Fluid Findings in Aseptic Versus Bacterial Meningitis. Pediatrics. 2000:105;316.
  6. Kanegaye JT. Lumbar Puncture in Pediatric Bacterial Meningitis; Defining the Time Interval for Recovery of CSF Pathogens After Parental Antibiotic Treatment. Pediatrics. 2001;108:1169. 
  7. Garges H. et al. Neonatal Meningitis: What is the Correlation  Among Cerebrospinal Fluid Cultures, Blood Cultures, and Cerebrospinal Fluid Parameters. Pediatrics, April 2006. 
  8. Gardner, P. Prevention of Meninogococcal Disease. New England Journal of Medicine. 2006. 
  9. Mann K. and Jackson MA. Meningitis. Pediatrics in Review December 2008  
  10. Kestenbaum e tal. Defining Cerebrospinal Fluid White Blood Cell Count Reference Values in Neonates and Young Infants. Pediatrics. February 2010.  

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