Meningitis and Encephalitis:

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Meningitis and Encephalitis

• Diagnosis and Treatment Update

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Definitions

• Meningitis inflammation of the meninges
• Encephalitis infection of the brain parenchyma
• Meningoencephalitis inflammation of brain
  meninges
• Aseptic meningitis inflammation of meninges
  with sterile CSF

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Symptoms of meningitis

• Fever
• Altered consciousness, irritability, photophobia
• Vomiting, poor appetite
• Seizures 20 - 30
• Bulging fontanel 30
• Stiff neck or nuchal rigidity
• Meningismus (stiff neck Brudzinski Kernig
  signs)

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Clinical signs of meningeal irritation
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Diagnosis lumbar puncture

• Contraindications
• Respiratory distress (positioning)
• ? ICP reported to increase risk of herniation
• Cellulitis at area of tap
• Bleeding disorder

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CSF evaluation
Condition WBC Protein (mg/dL) Glucose (mg/dL)
Normal lt7, lymphs mainly 5-45 gt50
Bacterial, acute 100 60K PMNs 100-500 Low
Bacterial, part rxd 1 10,000 100 Low to normal
TB 10 500 100-500 lt50
Fungal 25 500 25-500 lt50
Viral lt1000 50-100 Normal
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CSF Gram stain
Hemophilus influenza (H flu)
Strep pneumoniae
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Not addressed

• Indwelling CNS catheters
• S/P cranial surgery
• Anatomic defects predisposing to meningitis
• Immunocompromised patients
• Abscesses

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Bacterial meningitis

• 3 - 8 month olds at highest risk
• 66 of cases occur in children lt5 years old

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Bacterial meningitis - Organisms

• Neonates
• Most caused by Group B Streptococci
• E coli, enterococci, Klebsiella, Enterobacter,
  Samonella, Serratia, Listeria
• Older infants and children
• Neisseria meningitidis, S. pneumoniae,
  tuberculosis, H. influenzae

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Bacterial meningitis Clinical course

• Fever
• Malaise
• Vomiting
• Alteration in mental status
• Shock
• Disseminated intravascular coagulation (DIC)
• Cerebral edema
• Vital signs
• Level of mentation

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Increased intracranial pressure (ICP)

• Papilledema
• Cushings triad
• Bradycardia
• Hypertension
• Irregular respiration
• ICP monitor (not routine)
• Changes in pupils

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? ICP treatment

• 3 NaCl, 5 cc/kg over 20 minutes
• May utilize osmotherapy - if serum osms lt320
• Mild hyperventilation
• PaCO2 lt28 may cause regional ischemia
• Typically keep PaCO2 32-38 torr
• Elevate HOB 30o

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Meningitis - Fluid management

• Restore intravascular volume perfusion
• Monitor serum Na (osmolality, urine Na)
• If serum Na lt135 mEq/L then fluid restrict
  (2/3x), liberalize as Na improves
• If severely hyponatremic, give 3 NaCl
• SIADH
• 4 - 88 in bacterial meningitis
• 9 - 64 in viral meningitis
• Diabetes insipidus
• Cerebral salt wasting

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Meningitis - Treatment duration

• Neonates 14 21 days
• Gram negative meningitis 21 days
• Pneumococcal, H flu 10 days
• Meningococcal 7 days

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Bacterial Meningitis - TreatmentNeonatal (lt3
mo)

• Ampicillin (covers Listeria)
• Cefotaxime
• High CSF levels
• Less toxicity than aminoglycosides
• No drug levels to follow
• Not excreted in bile ? not inhibit bowel flora

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Meningitis - Acute complications

• Hydrocephalus
• Subdural effusion or empyema 30
• Stroke
• Abscess
• Dural sinus thrombophlebitis

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Bacterial meningitis - Outcomes

• Neonates 20 mortality
• Older infants and children
• lt10 mortality
• 33 neurologic abnormalities at discharge
• 11 abnormalities 5 years later
• Sensorineural hearing loss 2 - 29

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Bacterial meningitis - children

• Strep pneumoniae
• Neisseria meningitidis
• TB
• Hemophilus influenza

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Pneumococcal meningitis
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Antibiotic susceptibility

• Susceptible
• Non-susceptible
• Resistant

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Pneumococcal resistance

• Strep pneumococcus - most common cause of
  invasive bacterial infections in children gt2
  months old
• Incidence of PCN-, cefotaxime-
  ceftriaxone-nonsusceptible isolates has ?d to
  40
• Strains resistant to PCN, cephalosporins, and
  other ?-lactam antibiotics often resistant to
  trimethoprim-sulfamethoxazole (Bactrim,
  Septra), erythromycin, chloramphenicol,
  tetracycline

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Mechanism of resistance

• PCN-binding proteins synthesize peptidoglycan for
  new cell wall formation
• PCN, cephalosporins, and other ?-lactam
  antibiotics kill S pneumoniae by binding
  irreversibly to PCN-binding proteins located in
  the bacterial cell wall
• Chromosomal changes can cause the binding
  affinity for the ?-lactam antibiotics to decrease

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Pneumococcal meningitis Mgmt

• Vancomycin cefotaxime or ceftriaxone, if gt 1
  month old
• If hypersensitive (allergic) to ?-lactam
  antibiotics, use vancomycin rifampin
• D/C vancomycin once testing shows
  PCN-susceptibility
• Consider adding rifampin if susceptible
  condition not improving, or cefotaxime or
  ceftriaxone MIC high
• Not vancomycin alone

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Antibiotic use inPneumococcal meningitis

• PCN-susceptible organism
• PenG 250,000 - 400,000 U/kg/day ? Q 4 - 6 h
• Ceftriaxone 100 mg/kg/day ? Q 12 - 24 h
• Cefotaxime 225 - 300 mg/kg/day ? Q 8 h
• Chloramphenicol 50 - 100 mg/kg/day ? Q 6 h
• Adequate cephalosporin levels in CSF 2.8 hours
  after dose administration

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Vancomycin use inpneumococcal meningitis

• Combination therapy since late 90s
• At initiation-
• Baseline urinalysis
• BUN and creatinine
• Enters the CSF in the presence of inflamed
  meninges within 3 hours
• Should not be used as solo agent, but with
  cephalosporin for synergy

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Vancomycin use inpneumococcal meningitis

• Vancomycin 60 mg/kg/day ? Q 6 h
• Trough levels immediately before 3rd dose
• (10-15 mcg/mL or less)
• Peak serum level 30-60 minutes after completion
  of a 30-minute infusion
• (35-40 mcg/mL)

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Other antibiotics inpneumococcal meningitis
(resistant)

• Rifampin
• 20 mg/kg/day ? Q 12
• Not a solo agent
• Slowly bactericidal

• Meropenem
• Carbapenem
• 120 mg/kg/day ? Q 8 h
• ? seizure incidence, ? not generally used in
  meningitis
• Resistance reported

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Dexamethasone use in meningitis

• Consider if H flu S pneumo meningitis gt 6 wks
  old 0.6 mg/kg/day ? Q 6h x 2d
• ? local synthesis of TNF-?, IL-1, PAF
  prostaglandins resulting in ? BBB permeability, ?
  meningeal irritation
• Debate if it ? incidence of hearing loss
• If used, needs to be given shortly before or at
  the time of antibiotic administration
• May adversely affect the penetration of
  antibiotics into CSF

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Pneumococcal meningitis - Treatment

• LP after 24-48 hours to evaluate therapy if
• Received dexamethasone
• PCN-non-susceptible
• MICs not available
• Childs condition not improving

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Infection control precautions(invasive
pneumococcus)

• CDC recommends Standard Precautions
• Airborne, Droplet, Contact are NOT recommended
• Nasopharyngeal cultures of family members and
  contacts is NOT recommended
• No isolation of contacts
• No chemoprophylaxis for contacts

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Meningococcal meningitis

• Neisseria meningitidis
• 10 - 15 with chronic throat carriage
• Outbreaks in households, high schools, dorms
• Accounts for lt5 of cases
• 2,400 - 3,000 cases occur in the USA each year
• Peaks lt2 years of age 15-24 years

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Meningococcal disease

• Can cause purulent conjunctivitis, septic
  arthritis, sepsis /- meningitis
• Diagnose presence of organism (Gram negative
  diplococci) via
• CSF Gram stain, culture
• Sputum culture
• CSF (not urine) Latex agglutination
• Petechial scrapings
• Buffy coat Gram stain

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Meningococcemia - Petechiae
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Meningococcemia - Purpura fulminans
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Meningococcemia - Isolation

• Capable of transmitting organism up to 24 hours
  after initiation of appropriate therapy
• Droplet precautions x 24 hours, then no isolation
• Incubation period 1 - 10 days, usually lt4 days

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Meningococcemia - Treatment

• Antibitotic resistance rare
• Antibitotics
• PCN
• Cefotaxime or Ceftriaxone
• Patient should get rifampin prior to discharge

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Meningococcal disease - Care takers

• Day care where child attends gt25 h/wk, kids are
  gt2 years old, 2 cases have occurred
• Day care where kids not all vaccinated
• Persons who have had intimate contact w/ oral
  secretions prior during 1st 24 h of antibiotics
• Intimate contact 300-800x risk
• (kissing, eating/ drinking utensils,
  mouth-to-mouth, suctioning, intubating)

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Meningococcemia - Prophylaxis

• No randomized controlled trials of effectiveness
• Treat within 24 hours of exposure
• Vaccinate affected population, if outbreak

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Meningococcemia - Prophylaxis

• Rifampin
• Urine, tears, soft contact lenses orange OCPs
  ineffective
• lt1 mo 5 mg/kg PO Q 12 x 2 days
• gt1 mo 10 mg/kg (max 600 mg) PO Q 12 x 2 days
• Ceftriaxone
• ?12 y 125 mg IM x 1 dose
• gt12 y 250 mg IM x 1 dose
• Ciprofloxacin
• ?18 y 500 mg PO x 1 dose

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Meningococcal meningitis - Outcomes

• Substantial morbidity 11 - 9 of survivors have
  sequelae
• Neurologic disability
• Limb loss
• Hearing loss
• 10 case-fatality ratio for meningococcal sepsis
• 1 mortality if meningitis alone

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TB meningitis

• Children 6 months 6 years
• Local microscopic granulomas on meninges
• Meningitis may present weeks to months after
  primary pulmonary process
• CSF
• Profoundly low glucose
• High protein
• Acid-fast bacteria (AFB stain)
• PCR
• Steroids antimicrobials

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Aseptic vs. partially treated bacterial meningitis

• Aseptic much more common
• Gram stain positive CSF
• 90 - 100 in young patients
• 50 - 68 positive in older children
• If CSF fails to show organisms in a pretreated
  patient, then very unlikely that organism is
  resistant

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Viral meningitis

• Summer, fall
• Severe headache
• Vomiting
• Fever
• Stiff neck
• CSF - pleocytosis (monos), NL protein, NL glucose

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Etiology viral meningitis

• Enteroviruses predominate
• Spring, summer
• Oral-fecal route
• initial GI symptoms
• Meningitic symptoms appear 7-10 days after
  exposure

• Less common
• Mumps
• HIV
• Lymphocytic choriomeningitis
• HSV-2

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Other causes of aseptic meningitis

• Leptospira
• Young adults
• Late summer, fall
• Conjunctivitis, splenomegaly, jaundice, rash
• Exposure to animal urine
• Lyme Disease (Borrelia burgdorferi)
• Spring-late fall
• Rash, cranial nerve involvement

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Viral meningitis - Treatment

• Supportive
• No antibiotics
• Analgesia
• Fever control
• Often feel better after LP
• No isolation - Standard precautions

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Viral meningitis - Outcomes

• Adverse outcomes rare
• Infants lt1 year have higher incidence of speech
  language delay

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Meningoencephalitis - etiology

• Herpes simplex type 1
• Rabies
• Arthropod-borne
• St. Louis encephalitis
• La Crosse encephalitis
• Eastern equine encephalitis
• Western equine encephalitis
• West Nile

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Herpes simplex 1 encephalitis

• Symptoms
• Depressed level of consciousness
• Blood tinged CSF
• Temporal lobe focus on CT scan or EEG
• PCR
• Neonates typically will have cutaneous vessicles
• Treatment - IV acyclovir

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West Nile Virus

• Via bite of infected mosquito
• Incubation period 3 - 14 days
• 1 in 150 infected persons get encephalitis
• 4 of those are lt20 years of age
• H/A, fever, neck stiffness, stupor, coma,
  convulsions, weakness, paralysis
• Supportive therapy
• Mortality 9

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West Nile Virus
MMWR Dec 2002 511129-33
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Summary

• Antibiotics ASAP, even if LP not yet done
• Vanco cephalosporin until some identification
  known
• CSF, Latex, exam
• Isolate if bacterial x 24 hours, Universal
  Precautions
• Monitor for status changes
• Pupils, LOC, HR, BP, resp
• Seizures
• Hemodynamics
• DIC, coagulopathy
• Fluid, electrolyte issues

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