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Flashcards in CNS Infection Deck (19):
1

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)

2

Acute bacterial meningitis: top 3 causal organisms

(>80% due to 3 organisms):
o Streptococcus pneumonia
o Neisseria meningitides
o Haemophilus influenza type b

3

N. meningitidis: appearance

Gram-negative cocci in pairs

4

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

5

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

6

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)

7

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

8

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

9

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)

10

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

11

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

12

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

13

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

14

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)

15

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

16

Listeria monocytogenes: risk groups

Pregnant women (because CMI is mildly impaired)

Neonates
Sepsis syndrome
• Associated with prematurity
• From in utero infection)
Meningitis ~ 2 weeks after birth
• From contacting organism at time of birth)

Older adults with decreased immunity

17

Listeria monocytogenes: major diseases

Meningitis
• 20% of infections in neonates and elderly
• Subacute infection with classic symptoms (fever, meningismus, altered mental status, seizures, other neurological deficits)

Febrile gastroenteritis
• Fever, watery diarrhea, nausea, headache, myalgia and arthralgia (6 hours – 10 days incubation period)
• Symptoms last 1-3 days
• May precede CNS infection

18

Listeria monocytogenes: treatment

o Meningitis = IV ampicillin or trimethoprim-sulfamethoxazole
o GI illness = self limited (no antibiotics needed)

19

Listeria monocytogenes: prevention

o Proper food handling
o Avoid unpasteurized milk and uncooked meat
o Prophylaxis in transplant patients
o No vaccine