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Flashcards in CNS Infection Deck (19):

Acute bacterial meningitis: Definition and Sequelae

o Inflammation of the leptomeninges due to bacterial infection that occurs on order of hours to days

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

• 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

• Adhesins that enhance mucosal colonization


N. meningitidis: Major diseases

• 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

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)

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.

-Glucose: low
-Protein: high
-Cell count: high
-Differential: most neutrophils

-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

o Decreases morbidity and mortality
• Dexamethasone decreases neurologic sequelae (very strong evidence with H. influenzae)
• Begin dexamethasone 15-20 min before antibiotics
• 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

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


Listeria monocytogenes: risk groups

Pregnant women (because CMI is mildly impaired)

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


Listeria monocytogenes: major diseases

• 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


Listeria monocytogenes: treatment

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


Listeria monocytogenes: prevention

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