Meningitis Dr Michael Prentice

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Meningitis

• Presented By
• Afshin Shiva, Pharm.D.
• PGY2 Resident of clinical Pharmacy

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Famous People Whose Lives Were Touched by
Meningitis

• Francisco Goya (C18 painter) became deaf at age
  47 possibly due to meningitis. Source PubMed
• Mark Twain (American humourist and author) had a
  daughter Suzy who died in 1896 while Twain was in
  England. Source The Mark Twain House Museum
• Spice Girl Victoria "Posh Spice" Beckham had
  viral meningitis in 2000. Source BBC News

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Objectives

• Define meningitis
• Describe prevalence
• Explain pathophysiology
• Identify Clinical Manifestations
• Define Appropriate Treatment
• Describe Methods of Prevention

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What is meningitis?
The brain and spinal cord are covered by 3
connective tissue layers collectively called the
meninges which form the blood-brain barrier.

• -the pia mater (closest to the CNS)
• the arachnoid mater
• the dura mater (farthest from the CNS).
• The meninges contain cerebrospinal fluid (CSF).
• Meningitis is an inflammation of the
• meninges, which, if severe, may become
• encephalitis, an inflammation of the brain.

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Anatomy

• Meninge shock absorber
• Dura mater
• Arachnoid
• Pia mater

Epidural
Subdural
Leptomeninge
Subarachnoid
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Meningitis
Definition    Meningitis is an infection which
causes inflammation of the membranes covering
the brain and spinal cord. Non-bacterial
meningitis is often referred to as aseptic
meningitis eg. viral meningitis Bacterial
meningitis may be referred to as purulent
meningitis.
Causes and risks The most common causes of
meningitis are viral infections that usually
resolve without treatment. Bacterial infections
of the meninges are extremely serious illnesses,
and may result in death or brain damage even if
treated.
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Types of Meningitis
Bacterial Meningitis
Caused by virus. Less severe Resolves
without specific treatment within a week or
two Also called as aseptic meningitis Eg
Enteroviruses
Caused by bacteria Quite severe and may
result in a) brain damage b) hearing
loss c) learning disability It would also
causes death!
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Microbiology

• Neonates (infants lt1 months)
• Most caused
• Streptococus B (Agalactiie, )
• Coliform (E-coli)
• Listeria monocytogenesis
• Acquired
• birth canal
• Hospital invirontment
• Case fatality rates
• group B streptococci gt20
• gram-negative bacilli 30

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Microbiology

• Infants
• Caused by
• Haemophilus influenzae
• Streptococcus pneumoniae
• Neisseria meningitidis.

• Up to 45 of all cases before 1985 were by H.
  influenzae type b (Hib).From 1987 through 1997,
  however, Hib meningitis cases in children lt5
  years of age decreased by 97.
• most cases now are observed in adults.

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Microbiology

• Adults and children
• most often is caused by
• S. pneumoniae (the pneumococcus)
• N. meningitidis (the meningococcus)
• Meningococci common 5 to 30 y
• pneumococci predominant gt30 y
• Traditionally susceptible to penicillin,
  Pneumococcal strains showing penicillin
  resistance
• In the past several years, meningococcal
  meningitis has been occurring in clusters within
  the general population with increased frequency.

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Microbiology

• The elderly
• most susceptible
• S. pneumoniae (the pneumococcus)
• N. meningitidis (the meningococcus)
• Enteric gram-negative bacilli (e.g., E. coli,
  Klebsiella pneumoniae)
• L. Monocytogenes
• Mortality higher than in other age groups

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Prevalence

• 1806 1st epidemic in America Medfield MA
• Incidence
• 2.5 to 3.5 cases per 100,000 people
• 0.16 to 0.45 per 1,000 live births
• Approximately 1.2 million cases of bacterial
  meningitis occur annually worldwide
• Common Organisms
• 1986 - H. influenzae (45), S. pneumoniae (18),
  N. meningitidis
• (14)
• 1995 - S. pneumoniae (47), N. meningitidis
  (25),
• Listeria monocytogenes (8),
  H.influenzae (7)

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Pathophysiology

• Hematogenous spread (most common)
• blood to subarachnoid space
• Mechanical disruption
• Fracture of the base of the skull
• Direct extension from ear, mastoid air cells,
  sinuses, orbit or other adjacent structure

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Symptoms and Signs in Patients with Bacterial
Meningitis

• Headache 90
• Fever 90
• Stiff neck (Nuchal rigidity) 85
• Altered mental status 80
• Kernigs or Brudzinskis sign 50
• Seizures 30
• Other
• NV (35), photophobia, papilledma, irritability,
  diffuse rash, petechia, purpura

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Laboratory Data

• Blood Tests
• CBC with diff
• Blood culture
• Coags if any petechiae or purpura noted
• CSF
• Cell Count
• Glucose and protein
• Gram stain
• Culture and sensitivity

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CSF

• Origin (Choroid Plexus in I,II Ventricle),
  unilateral, 550ml/d
• Adult150ml
• Volume Infant60-100 ml (5 mg
  Gentamycin Adult 33mcg/ml)
• Neonate40-60ml
• PH 7.3
• Lytes ltserum
• Pr. lt50mg/dl
• Glu. 60 plasma
• WBC lt5 cell/mm3

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CSF Findings
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Diagnosis

• Clinical features
• CT scan may show no evidence of a mass
• Cloudy spinal fluid with increased numbers of
  white cells, high protein and low glucose
• Organisms seen on gram stain (may be negative
  when antibiotics have been administered)
• CSF culture
• Throat and stool culture for suspected viral
  meningitis

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Treatment General Principle

• Avoidance of delay
• Emperical antibiotic

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Treatment Considerations

• Allergies
• CSF Penetration
• Empiric Therapy Age specific
• Dosing
• Cultures/Sensitivities
• Pathogen Specific Therapy
• Duration of Therapy

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CSF Penetration

• Lipophilicity
• Chloramphenicol
• Protein binding
• Ceftriaxone
• Molecular size
• Vancomycin

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Empiric Therapy Age specific
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Adjunctive Treatment

• Dexamethasone Controversial
• Rationale inflammatory cytokines have role in
  pathophysiology of bacterial meningitis
• Debate adjunctive therapy could reduce
  penetration of antibiotics into the CNS
• Clinical trials show benefit reduced audiologic
  and neurologic complications
• Benefit seen only in patients infected with H.
  influenza
• Benefit seen in patients infected with S.pneumo
  but not statistically significant
• AAP recommends initiation 30 minutes prior to 1st
  dose of antibiotics
• Dose 0.15 mg/kg/dose IV q6h x 4 days

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Optimization of Antibiotic Therapy

• Once culture information is available and
  organism has been identified, review antibiotic
  choices to ensure appropriate treatment
• Determine duration of therapy based on organism
  identified

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Pathogen-Specific Therapy
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AmpicillinSpectrum Group B Strept, S. pneumo,
Listeria, N. meningitidis

• Contraindications
• Hypersensitivity to penicillin
• Adverse Events
• Injection site pain
• Rash
• Diarrhea
• Nausea/vomiting

• Class
• Penicillin
• Dosing
• 200 mg/kg/day IV Q6h
• Max Dose 12 g/day
• Adjust in renal impairment

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PenicillinSpectrum S. aureus, N. meningitidis

• Class
• Penicillin
• Dosing
• 300,000 400,000 units/kg/day IV Q4-6h
• Max Dose 24 MU/day

• Contraindications
• Hypersensitivity to penicillin
• Adverse Events
• Rash
• Diarrhea
• Nausea and Vomiting

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Cefotaxime (Claforan) Spectrum S. pneumo, N.
meningitidis, H.influenzae, E. coli

• Class
• Cephalosporin
• Dosing
• 200-300 mg/kg/day IV Q6h
• Max Dose 12 g/day

• Contraindications
• Hypersensitivity to cephalosporins
• Adverse Events
• Rash, Pruritus
• Diarrhea, colitis
• Injection site pain
• Nausea/vomiting

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Ceftriaxone (Rocephin)Spectrum S.pneumo,
N.meningitidis, H.influenzae, E. coli

• Class
• Cephalosporin
• Dosing
• 75 - 100 mg/kg/day IV q12h-QDay
• Max Dose 4 g/day

• Contraindications
• Hypersensitivity to cephalosporins
• Adverse Events
• Rash
• Diarrhea,
• Injections site pain
• Increased LFTs

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Vancomycin (Vancocin)Spectrum S.aureus,
S.pneumoniae

• Class
• Glycopeptide
• Dosing
• 60 mg/kg/day IV q8h
• No max dose but some references suggest 4g
• Check trough levels to determine appropriate
  dosing
• Trough should be gt 5 mcg/mL

• Contraindications
• Hypersensitivity to Vancomycin If red mans may
  slow infusion and adm over 2hrs
• Adverse Events
• Flushing
• Redmans syndrome,
• Neutropenia
• Vasculitis
• Nephrotoxicity/Ototoxicity

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Complications of Meningitis
One of the most common problems resulting from
meningitis is hearing loss. Anyone who has had
meningitis should take a hearing test.

• Young children
• Babyish behavior
• Forgetting recently learned skills
• Reverting to bed-wetting

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• Older people
• Lethargy
• Recurring headaches
• Difficulty in concentration
• Short-term memory loss
• Clumsiness
• Balance problems
• Depression

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Serious complications

• Other serious complications can include
• Brain damage
• Epilepsy
• Changes in eye sight

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Prevention

• N. meningitidis
• Prophylaxis of close contacts
• Rifampin
• lt 1 month old 10 mg/kg q24h x2 doses
• gt 1 month old 20 mg/kg q24h x 2 doses
• Adults 600 mg q12h x 4 doses
• Ceftriaxone 150 ,250 mg IM x 1 dose
• Ciprofloxacin 500 mg x 1 dose
• Immunizations
• Pneumococcal Vaccine for children lt 2 yrs
• Meningococcal Vaccine for all 11-12 year olds,
  unvaccinated adolsecents at high school entry,
  all college freshmen living in dormitories, and
  2 years at high risk

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Hib Vaccination

• for children gt 2 months
• HbOC Polyribosylribitol(PRP) diphthria toxin
  protein.
• PRP-T PRP tetanus toxin
• PRP-OMP PRP Outer memberane complex protein of
  N.meningits

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Mortality Meningitis
Nosocomial 35 Risk
Factors Relative Risk Age gt 60 2.1 Obtunded
Mental Status 3.0 Seizures 4.0
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