Post on 18-Jan-2016
transcript
Meningitis
Presented ByAfshin Shiva, Pharm.D.
PGY2 Resident of clinical Pharmacy
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
Objectives
• Define meningitis
• Describe prevalence
• Explain pathophysiology
• Identify Clinical Manifestations
• Define Appropriate Treatment
• Describe Methods of Prevention
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.
Anatomy• Meninge: shock absorber
Dura mater
Arachnoid
Pia mater
Epidural
Subdural
LeptomeningeSubarachnoid
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 risksThe 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.
For bacterial meningitis, it is also important to know which type of bacteria is causing the meningitis because antibiotics can prevent some types from spreading and infecting other people.
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!
Microbiology
• Neonates (infants <1 months):
Most caused: Streptococus B (Agalactiie, )
Coliform (E-coli) Listeria monocytogenesis
Acquired: birth canalHospital invirontment
Case fatality rates:group B streptococci: >20% gram-negative bacilli: 30%
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 <5 years of age decreased by 97%.
most cases now are observed in adults.
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: >30 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.
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
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%)
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
19
Pathogenic Event
Host Defense Bacterial Evasion Mechanism
Colonization andmucosal invasion,
1. Secretory IgA 2. Cellular cilia activity 3. Mucosal epithelium
IgA protease secretion Ciliostasis Adhesive pili
Survival in the blood stream
Activation of Complement Pathways
Blockage of Alternative Compliment Pathway by Mechanisms on the cell surface
Crossing the blood-brainbarrier
Cerebral endothelium Passage through tight junctions between cells, mechanism unknown
Survival within the CSF Poor opsonic activity Rapid bacterial replication
Symptoms and Signs in Patients with Bacterial Meningitis
Headache 90%
Fever 90%Stiff neck (Nuchal rigidity) 85%Altered mental status 80%Kernig’s or Brudzinski’s sign 50%Seizures 30%
Other: – N&V (35%), photophobia, papilledma, irritability, diffuse rash,
petechia, purpura
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
CSF• Origin :(Choroid Plexus in I,II Ventricle), unilateral, 550ml/d
Adult=150ml
Volume Infant=60-100 ml (5 mg Gentamycin :Adult = 33mcg/ml)
Neonate=40-60ml
PH = 7.3
Lytes = <serum
Pr. = <50mg/dl
Glu. = 60% plasmaWBC = <5 cell/mm3
CSF Findings
Microbial Etiology
WBC Count
(cells/mm3)
Predominant Cell
Type Protein GlucoseBacterial >500 PMN Elevated –
Fungal 10–500 MN Elevated Variable
Viral 10–200 PMN or MN
Variable Normal
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
Treatment: General Principle
• Avoidance of delay• Emperical antibiotic
Treatment Considerations
• Allergies• CSF Penetration• Empiric Therapy: Age specific• Dosing• Cultures/Sensitivities• Pathogen Specific Therapy• Duration of Therapy
CSF Penetration
• Lipophilicity:
Chloramphenicol
• Protein binding :
Ceftriaxone
• Molecular size:
Vancomycin
Empiric Therapy: Age specificAge Group or Predisposing
ConditionRecommended
Therapy Alternative TherapyNeonates (<1
mo)Ampicillin + cefotaxime Ampicillin +
gentamicinInfants and
children (1–23 mons)
Cefotaxime or ceftriaxone + vancomycin
Vancomycin + rifampin + aztreonam
Older children and adults (2–50
yr)
Cefotaxime or ceftriaxone + vancomycin
Vancomycin + rifampin + aztreonam
Elderly (>50 yr) Ampicillin, cefotaxime, or ceftriaxone + vancomycin
Vancomycin + TMP-SMX + aztreonam
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
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
Pathogen-Specific Therapy
Organism Duration
Neisseria meningitis 7-10 days
H. Influenzae 7-10 days
Streptococcus pneumoniae 10-14 days
Group B Streptococcus 14-21 days
Listeria monocytogenes 14-21 days
Other gram negative bacilli 21 days
AmpicillinSpectrum: Group B Strept, S. pneumo, Listeria, N.
meningitidis
• Class– Penicillin
• Dosing– 200 mg/kg/day IV Q6h – Max Dose = 12 g/day– Adjust in renal
impairment
• Contraindications– Hypersensitivity to
penicillin
• Adverse Events– Injection site pain – Rash– Diarrhea
– Nausea/vomiting
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
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
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 LFT’s
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 > 5 mcg/mL
• Contraindications– Hypersensitivity to
Vancomycin – If red man’s may slow infusion and adm over 2hrs
• Adverse Events– Flushing– Redman’s syndrome,– Neutropenia– Vasculitis – Nephrotoxicity/Ototoxicity
Complications of MeningitisComplications of Meningitis
• Young children:
1. Babyish behavior2. Forgetting recently
learned skills3. Reverting to bed-wetting
One of the most common problems resulting from meningitis is hearing loss. Anyone who has had meningitis should take a hearing test.
• Older people:1. Lethargy 2. Recurring headaches 3. Difficulty in
concentration 4. Short-term memory
loss 5. Clumsiness 6. Balance problems 7. Depression
Serious complicationsSerious complications
• Other serious complications can include:
1. Brain damage
1. Epilepsy
2. Changes in eye sight
Prevention
• N. meningitidis Prophylaxis of close contacts
• Rifampin • < 1 month old: 10 mg/kg q24h x2 doses • > 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 < 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
Hib Vaccination
for children > 2 monthso HbOC: Polyribosylribitol(PRP)+ diphthria toxin protein.o PRP-T: PRP + tetanus toxino PRP-OMP: PRP + Outer memberane complex protein of N.meningits
ScheduleVaccine (Trade
Name) 2 Months 4 Months 6 Months 12 Months 15 Months
HbOC (HibTITER)Dose 1 Dose 2 Dose 3
—Booster
PRP-T (ActHIB) Dose 1 Dose 2 Dose 3 — Booster
PRP-OMP (PedvaxHIB)
Dose 1 Dose 2 — Booster —
Mortality Meningitis
Community Acquired
Gram-negative
1962-1970 24% 21%
1971-1979 26% 34%
1980-1986 24% 13%
Nosocomial 35%
Risk Factors Relative RiskAge > 60 2.1Obtunded Mental Status 3.0Seizures 4.0