Pyogenic Meningitis - Microbiology

Gross Pathology

Causative Organisms by Age Group

• Robbins & Kumar Basic Pathology, p. 833; Robbins & Cotran, p. 1164; Rosen's Emergency Medicine, p. 2268

Key Organisms - Details

1. Streptococcus pneumoniae (Pneumococcus)

• Most common overall cause in adults, accounting for ~70% of cases in developed countries following Hib vaccination
• Gram-positive, lancet-shaped diplococci
• Exudate is densest over cerebral convexities near the sagittal sinus
• Large amounts of capsular polysaccharide can produce gelatinous exudate and subsequent chronic adhesive arachnoiditis with hydrocephalus
• Highest rates of residual neurologic deficits among survivors

2. Neisseria meningitidis (Meningococcus)

• Gram-negative diplococci
• Predominant pathogen in children and young adults; often causes outbreaks (military barracks, college dormitories)
• Major serogroups: A, B, C, W-135, Y
  • Group B: prevalent in Europe
  • Group C: common in the United States
• Feared complication: Waterhouse-Friderichsen syndrome - meningococcal (and pneumococcal) septicemia causing bilateral hemorrhagic adrenal infarction
• Conjugate vaccine covers serogroups A, C, Y, W-135; separate vaccine for serogroup B

3. Haemophilus influenzae type b (Hib)

• Gram-negative coccobacillus; requires factors X (hemin) and V (NAD) - grown on chocolate agar
• Exudate is typically basal in distribution
• Incidence has dropped sharply since introduction of the Hib vaccine
• Now affects primarily unvaccinated children and older adults (as illustrated by the nursing-home case above with gram-negative rods in CSF - Medical Microbiology 9e, p. 293)

4. Listeria monocytogenes

• Gram-positive short rod, motile
• Affects neonates and adults >60 years; emerging as one of the most common causes in developed countries
• Highest mortality rate of all causes (up to 27%)
• Requires ampicillin for coverage (cephalosporins are not effective)

5. Group B Streptococcus (S. agalactiae)

• Gram-positive cocci in chains
• Major neonatal pathogen along with E. coli
• Acquired during passage through the birth canal

6. Escherichia coli

• Gram-negative rod
• Key neonatal pathogen; K1 capsular antigen is a major virulence factor

Pathogenesis

1. Nasopharyngeal colonization - most organisms (especially N. meningitidis, S. pneumoniae, Hib) colonize the nasopharyngeal mucosa first
2. Mucosal invasion - bacteria cross epithelial barriers; polysaccharide capsules protect against phagocytosis
3. Bacteremia - organisms seed the bloodstream
4. Blood-brain barrier (BBB) crossing - bacteria enter the CSF; host defense mechanisms within CSF are largely ineffective (low immunoglobulin, low complement levels)
5. Bacterial proliferation in CSF - triggers leukocyte recruitment
6. Inflammatory cascade - cytokines (TNF-α, IL-1, IL-6) released; increased BBB permeability, cerebral vasculitis, edema, raised intracranial pressure
7. Decreased cerebral blood flow - can cause cerebral hypoxia and infarction

• Rosen's Emergency Medicine, p. 2268

Morphology / Pathology

• Leptomeninges over the brain surface are covered with suppurative exudate
• Meningeal vessels engorged and prominent
• Distribution varies: basal (Hib meningitis) vs. over cerebral convexities (pneumococcal)
• In fulminant cases: inflammation extends to ventricles (ventriculitis)

• Neutrophils fill the subarachnoid space; concentrated around leptomeningeal blood vessels
• Gram stain shows variable numbers of bacteria
• In severe cases: neutrophil infiltration of leptomeningeal vein walls, focal cerebritis
• Secondary vasculitis and venous thrombosis can cause hemorrhagic cerebral infarction

• Leptomeningeal fibrosis → hydrocephalus
• Pneumococcal-specific: gelatinous polysaccharide exudate → chronic adhesive arachnoiditis
• Robbins & Cotran, p. 1165

CSF Findings in Bacterial (Pyogenic) Meningitis

• Washington Manual of Medical Therapeutics, p. 520

Summary of Epidemiological Impact of Vaccination

• Hib vaccine: dramatically reduced H. influenzae meningitis in children
• Pneumococcal conjugate vaccine (PCV): reduced pneumococcal meningitis but S. pneumoniae remains the most common cause in adults (~70%)
• Meningococcal conjugate vaccine (serogroups A, C, Y, W-135) + separate serogroup B vaccine: highly effective, but not yet broadly distributed in developing countries
• Net effect: incidence down to 0.5-1.5 per 100,000 adults in developed countries; mortality (~15%) largely unchanged
• Goldman-Cecil Medicine, p. 3997-3999