CNS Infection Flashcards
Acute bacterial meningitis: Definition and Sequelae
Definition:
o Inflammation of the leptomeninges due to bacterial infection that occurs on order of hours to days
Sequelae: o Death o Hearing loss o Seizures o Cognitive dysfunction (learning disorders, speech problems)
Route of infection:
o Most cases = blood borne
o Small minority = direct extension and invasion (from sinuses and ear infection)
Acute bacterial meningitis: top 3 causal organisms
(>80% due to 3 organisms):
o Streptococcus pneumonia
o Neisseria meningitides
o Haemophilus influenza type b
N. meningitidis: appearance
Gram-negative cocci in pairs
N. meningitidis: Virulence factors
Capsular polysaccharide
• Major virulence factor
• At least 13 types
Endotoxin
• Lipid A (component of LPS) = activates complement cascade → IL-1 and TNF release
• Leads to sepsis & Disseminated intravascular coagulation (DIC)
IgA 1 Protease
• Cleaves secretory IgA
• Able to survive on mucosa of respiratory tract
Pili
• Adhesins that enhance mucosal colonization
N. meningitidis: Major diseases
Meningitis
• Leading cause of acute bacterial meningitis in adolescents and young adults (10% fatality rate)
• Distinguishing feature = skin lesions (rash)
Waterhouse - Friderichsen syndrome
o Shock and DIC lead to adrenal hemorrhage
o Death may occur within hours
Identify the major etiologic causes of acute bacterial meningitis according to the following four age groups: neonates, children, adults, and the elderly
Neonates
o Streptococcus agalactiae
o Listeria monocytogenes
o E. coli
Children over 1 month
o Streptococcus pneumonia
o Neisseria meningitides
o Haemophilus influenzae type b
Adults (less than 50)
o Neisseria meningitides
o Streptococcus pneumonia
Elderly (over 50) o Streptococcus pneumonia o Listeria monocytogenes o Neisseria meningitides o Haemophilus influenzae type b o Gram negative rods (rare)
Common features and sites of infection of the 3 major bacterial meningitis pathogens:
Human reservoir
Transmission via respiratory droplets
Nasopharyngeal colonization 3 possible outcomes: • Organism being cleared • Asymptomatic carriage • Clinical disease
Sites of infection and clinical disease:
o Leptomeninges (all three)
o Lung (S. pneumoniae & H. influenzae)
o Middle Ear (S. pneumoniae & H. influenzae)
o Sinuses (S. pneumoniae & H. influenzae)
o Epiglottis (primarily H. influenzae)
Pathogenesis
o Organisms in respiratory droplets attach to mucosa
o Evade phagocytosis
o Multiply in nasopharynx
o May travel to lung, middle ear, sinuses, or invade bloodstream
Capsular polysaccharide
o Major virulence factor
• Prevents antibody-independent opsonization (C3b) → Evades phagocytosis
Principle immunogen
• Exposure to specific capsular antigens → development of protective antibodies
• Exposure to normal flora also results in some protection from cross-reacting antibodies
• Thus = adults are more protected than children
Describe the signs and symptoms of acute bacterial meningitis
o Headache (>90%) o Fever (>90%) o Meningismus (>85%) = Headache, neck stiffness from pus under spinal column = stretches it o Altered sensorium (>80%)
Kernig’s sign (>50%)
• Patient supine = flex hip and knee
• Attempt to extend knee
• In meningeal irritation → resisted, causes pain in hamstrings
Brudzinski’s sign (>50%)
• Patient supine = attempt to flex neck
• In meningeal irritation → involuntary flexion of hips
o Vomiting (35%) o Seizures (30%) o Focal findings (15%) o Papilledema (<1%) = Bulging optic disc
What to do if suspect bacterial meningitis?
Critical = perform lumbar puncture
• CT before only if coma, focal neurologic findings or papilledema
Look for evidence of increased intracranial pressure:
• Increased opening pressure
• Cranial nerve VI palsy
• Brain edema by CT scan
• Papilledema
If increased pressure = don’t perform lumbar puncture = could cause brain herniation through foramen magnum
Test CSF for: • Glucose • Protein • Cell count with differential • Cytospin Gram stain • Culture o Save tube for special tests (bacterial antigens, Lyme Western blot, PCR for TB, PCR for herpes simplex, Enterovirus)
Explain how one might differentiate between aseptic meningitis and acute bacterial meningitis.
Bacterial:
- Glucose: low
- Protein: high
- Cell count: high
- Differential: most neutrophils
Aseptic:
- Glucose: typically normal
- Protein: mildly elevated
- Cell count: mildly elevated
- Differential: mostly lymphocytes
Describe the principles of treatment of acute bacterial meningitis.
Key is to start therapy promptly
o Can’t wait for results from the micro lab
o Base therapy on presentation & epidemiology
Necessary antibiotic properties:
o Excellent penetration into the CSF
o Bactericidal activity
Factors that reduce antibiotic activity:
o Low pH of fluid, high protein, high temperature
Supportive therapy:
o Intubation and mechanical ventilation
o Fluid restriction (< 1500 ml/day in adults) = to control edema
o Seizure precautions + prophylaxis Mannitol 0.25 mg-0.50 g/kg IV boluses
• Osmotic diuresis to shrink swelling in brain
o Correct metabolic derangements
o If response is slow, repeat LP in 24-48 hours and look for parameningeal focus
Corticosteroids:
o Decreases morbidity and mortality
Children
• Dexamethasone decreases neurologic sequelae (very strong evidence with H. influenzae)
• Begin dexamethasone 15-20 min before antibiotics
Adults
• Now evidence in adults
• Vancomycin penetration into CSF may be decreased
Empiric therapy for acute bacterial meningitis
Neonates (age, < 1 month)
• Ceftriaxone (cover strep and meningococcus) plus Ampicillin (Listeria)
Children (age, > 1 month)
• Ceftriaxone plus Vancomycin (cover highly penicillin-resistant pneumococcus)
• Dexamethasone
Adults (age, < 50 years)
• Ceftriaxone + Vancomycin
• Dexamethasone
Adults (age, > 50 years)
• Ceftriaxone + Vancomycin + Ampicillin
• Dexamethasone
Discuss strategies that can be used to prevent infections caused by S. pneumoniae,
H. influenzae type b, and N. meningitidis.
Active immunization:
Haemophilus influenzae type b: Hib vaccine for all children
S. pneumonia:
• 23 – valent S. pneumoniae for high risk adults
• 13 – valent S. pneumoniae for high risk adults
• 13 – valent S. pneumoniae vaccine for all children
Meningococcus: Meningococcal vaccine for teens & high risk groups
Prophylaxis:
o Persons exposed to a case of meningococcemia
o Children exposed to a case of invasive H. influenzae
Listeria monocytogenes: characteristics
o Non-branching Gram-positive rod
o Tumbling motility at 25°C
o Likes to grow at refrigerator temperatures (ex: on lunch meats)
o Found in many environments (ex: soil, water, decaying vegetable matter, many different foods)
Listeria monocytogenes: pathogenesis
o Once ingested = gains access to cells via endocytosis
o Enters bloodstream = Reaches CNS and placenta
o Major virulence factor = Listeriolysin O –> Evades phagocytosis and intracellular killing
o Intracellular organism
• Infections correlate with cell-mediated immune function
