IC17 bacterial Meningitis

Question 1

What is the pathogenesis for bacterial meningitis? What are the source of infection?

Answer 1

Pathogenesis
Physiology:

• Meninges is a protective covering of the brain and the spinal cord
• 3 layers of meninges – dura mater, arachnoid, pia mater
• Leptomeninges (arachnoid and pia mater)
• CSF is in between arachnoid and pia mater
  Infection and inflammation of leptomeninges
  Commonly infect male and children

Source of infection:

• Para-meningeal focus spread –> Otitis media, pharynx, sinuses (ENT)
• Hematogenous spread (from respiratory tissues to bloodstream to CSF)
• Penetrating head trauma
• Anatomic defects in meninges
• Previous neurosurgical procedures

Question 2

What are the risk factors of bacterial meningitis?

Answer 2

1. Immune deficiency (HIV, corticosteroids, asplenia)
2. Close contact with individuals with bacterial meningitis
3. Travelling to an endemic area e.g. Africa
4. Infection at the nose, ear, or throat (Otitis media, pharyngitis, sinusitis)
5. Neurological surgery
6. CSF shunt (tube)
7. CSF fistula or leaks
8. Head trauma
9. Splenectomy (spleen v important in filtering microbes)
10. Congenital defects (Abnormal structures of the meninges)

Question 3

What are the clinical presentations of bacterial meningitis?

Answer 3

History taking
Systemic Signs: fever, chills
Classic Triad: headache, nuchal / neck rigidities, backache
Others: mental status changes(irritability), photophobia, nausea, vomiting, anorexia, poor feeding habits (infants), petechia, purpura (Neisseria meningitidis)

Physical Examination:

• Kernig’s sign –> lift one leg up such that it is perpendicular to the body and patient feels backache
• Brudzinski sign –> tilt head up and bend neck, hip and knee will bend as a reflex
• Bulging Fontane –> infants should have an open skull instead of a bulging one

Question 4

What are the objective evidence of bacterial meningitis?

Answer 4

1. *Blood culture
   a. Most would come back positive
2. *Lumbar puncture (draw fluid out from L3/L4 area)
   a. Elevated opening pressure
   b. CSF composition
   c. CSF gram stain and culture
   d. CSF PCR (to check a specific pathogen)

Normal (clear), Bacterial (turbid), Viral (clear):
Glucose 2.6-4.5
CSF:blood > 0.66 (~2/3)
Very low CSF:blood < 0.4
Normal or slightly low

Protein <0.4g/L
Very high >1.5 g/L
Normal or slightly raised

WBC <5 cells/mm3
WBC >100 cells/mm3
(mainly neutrophils, pleocytosis)
WBC (5-1000 cells/mm3)
(mainly lymphocytes)

3. Radiological test (CT/MRI)
   a. Not needed but usually do for differential diagnosis and complications
   b. Done prior to lumbar puncture when concerned about brain shift due to mass lesions, due to risk of brain herniation during LP
4. General lab test
   a. WBC, CRP, Procalcitonin
   b. Indicate systemic infection

Question 5

When should you start antibiotics for bacterial meningitis?

Answer 5

empiric start within 1 hour

Question 6

What are the likely pathogens that cause bacterial meningitis? What are the possible empiric therapy?

Answer 6

Neonates (<1month):

Pathogens:

• Group B Streptococcus (agalactiae)
• E. coli
• Listeria monocytogenes

Empiric therapy:

1. Ceftriaxone – Grp B strep, E. coli
   AND
2. Ampicillin – listeria monocytogenes

Infant (1-23 months)
Pathogens:

• Streptococcus pneumonia
• Neisseria meningitidis
• Grp B streptococcus
• E. coli

Empiric therapy:

1. Ceftriaxone – cover all
   AND
2. Vancomycin – in case have cephalosporin pen-resistant strep pneumonia

Children and adults (2-50 y/o):
Pathogens:

• Streptococcus pneumonia
• Neisseria meningitidis

Empiric therapy:

1. Ceftriaxone
   AND
2. Vancomycin

Older Adults (>50 y/o)
Pathogens:

• Streptococcus pneumonia
• Neisseria meningitidis
• Listeria monocytogenes
• Aerobic gram-negative bacilli e.g. E. coli, klebsiella

Empiric therapy:
All 3
1. Ceftriaxone
2. Vancomycin
3. Ampicillin

Question 7

What are the culture-directed therapy and duration for bacterial menigitis?

Answer 7

Pathogens, Antibiotics, Duration:

1. Streptococcus pneumonia
   Pen sus: Pen G / Ampicillin
   Pen resist: Ceftriaxone
   Pen and Cepha resist: Vancomycin + Rifampicin
   10-14 days
2. Neisseria meningitidis
   Pen sus: Pen / Ampicillin
   Pen resist or mild allergy: Ceftriaxone
   5-7 days
3. Listeria monocytogenes
   Pen sus: Pen G / Ampicillin
   Pen allergy: co-trimoxazole / meropenem
   21 days or more
4. Group B Streptococcus (agalactiae)
   Pen / Ampicillin
   Pen resist or mild allergy: Ceftriaxone
   14-21 days

IV Rifampicin 300mg BD

Question 8

What is the duration of treatment if no culture for bacterial meningitis?

Answer 8

at least 14 days of empiric therapy

Question 9

What are the characterisitics of good antibiotics for bacterial meningitis?

Answer 9

Characteristics of antibiotics given to treat bacterial meningitis:

1. Distribute to CSF well (high dose and IV)
2. Active against pathogen (indicated for)
3. Does not aggravate CNS morbidity (hearing impairment, cognitive impairment, seizures)
   a. E.g. don’t give high dose imipenem but high dose meropenem, since imipenem can lead to high risk of seizures

Question 10

What adjunctive therapy should be given for bacterial meningitis?

Answer 10

Adjunctive corticosteroid therapy
Benefits:

1. Lower hearing loss and neurological sequelae caused by Hemophilus influenza and Streptococcus pneumonia
2. Lower mortality caused by Streptococcus pneumonia

Risk:

1. Reduce antibiotic penetration (due to lower inflammation)
2. ADR – mental status changes, hyperglycemia, hypertension

Dose:
IV Dexamethasone 10mg Q6H up to 4 days
Give 10-20 mins before or same time as antibiotics use (at most 4-12 hours after starting antibiotic)

Give only if have bacterial meningitis (hemophilus influenza / S. pneumona) + > 6 weeks old

Stop dexamethasone:

• When no bacterial meningitis OR pathogen causing bacterial meningitis is NOT hemophilus influenza or streptococcus pneumonia

Question 11

How to monitor response to bacterial meningitis?

Answer 11

Step 4: Monitor Response
Therapeutic response:

• Improve within 48 hrs
• If don’t improve within 48 hours, do brain imaging to detect cerebrovascular complications e.g. stroke, brain abscess
• NO need lab test if clinically improve

ADR of antibiotics + Corticosteroids

Morbidity in bacterial meningitis:

• Neurological deficits: Hearing impairment, cognitive impairment and seizures
• Neurological and neuropsychological deficits –> impair daily life activities and QOL

Question 12

Why and what chemoprophylaxis should be given for bacterial meninigitis?

Answer 12

Antibiotic chemoprophylaxis regimen for individuals with close contact with meningococcal meningitis
Neisseria Meningitidis

• Close contact with meningococcal disease (especially household contact) can have 400-800 fold higher risk of getting meningococcal disease
• For close contacts (household or day care) and exposure to oral secretions of index case:

1. PO Rifampicin (adult) 600mg Q12h, 4 doses
   a. Children 10mg/kg
   b. Neonates (<1 month) 5mg/kg
2. PO Ciprofloxacin 500mg, 1 dose (adult)
3. IM ceftriaxone 125-250mg, 1 dose