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Meningitis and Encephalitis:. Diagnosis and Treatment Update. 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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meningitis and encephalitis

Meningitis and Encephalitis:

Diagnosis and Treatment Update

definitions
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
symptoms of meningitis
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)
diagnosis lumbar puncture
Diagnosis – lumbar puncture
  • Contraindications:
    • Respiratory distress (positioning)
    •  ICP reported to increase risk of herniation
    • Cellulitis at area of tap
    • Bleeding disorder
csf gram stain
CSF Gram stain

Hemophilus influenza

(H flu)

Strep pneumoniae

not addressed
Not addressed
  • Indwelling CNS catheters
  • S/P cranial surgery
  • Anatomic defects predisposing to meningitis
  • Immunocompromised patients
  • Abscesses
bacterial meningitis
Bacterial meningitis
  • 3 - 8 month olds at highest risk
  • 66% of cases occur in children <5 years old
bacterial meningitis organisms
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
bacterial meningitis clinical course
Bacterial meningitis – Clinical course
  • Fever
  • Malaise
  • Vomiting
  • Alteration in mental status
  • Shock
  • Disseminated intravascular coagulation (DIC)
  • Cerebral edema
    • Vital signs
    • Level of mentation
increased intracranial pressure icp
Increased intracranial pressure (ICP)
  • Papilledema
  • Cushing’s triad
    • Bradycardia
    • Hypertension
    • Irregular respiration
  • ICP monitor (not routine)
  • Changes in pupils
icp treatment
 ICP treatment
  • 3% NaCl, 5 cc/kg over ~20 minutes
  • May utilize osmotherapy - if serum osms <320
  • Mild hyperventilation
    • PaCO2 <28 may cause regional ischemia
    • Typically keep PaCO2 32-38 torr
  • Elevate HOB 30o
meningitis fluid management
Meningitis - Fluid management
  • Restore intravascular volume & perfusion
  • Monitor serum Na+ (osmolality, urine Na+):
    • If serum Na+ <135 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
meningitis treatment duration
Meningitis - Treatment duration
  • Neonates: 14 – 21 days
  • Gram negative meningitis: 21 days
  • Pneumococcal, H flu: 10 days
  • Meningococcal: 7 days
bacterial meningitis treatment neonatal 3 mo
Bacterial Meningitis - TreatmentNeonatal (<3 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
meningitis acute complications
Meningitis - Acute complications
  • Hydrocephalus
  • Subdural effusion or empyema ~30%
  • Stroke
  • Abscess
  • Dural sinus thrombophlebitis
bacterial meningitis outcomes
Bacterial meningitis - Outcomes
  • Neonates: ~20% mortality
  • Older infants and children:
    • <10% mortality
    • 33% neurologic abnormalities at discharge
    • 11% abnormalities 5 years later
  • Sensorineural hearing loss 2 - 29%
bacterial meningitis children
Bacterial meningitis - children
  • Strep pneumoniae
  • Neisseria meningitidis
  • TB
  • Hemophilus influenza
antibiotic susceptibility
Antibiotic susceptibility
  • Susceptible
  • Non-susceptible
  • Resistant
pneumococcal resistance
Pneumococcal resistance
  • Strep pneumococcus - most common cause of invasive bacterial infections in children >2 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
mechanism of resistance
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
pneumococcal meningitis mgmt
Pneumococcal meningitis – Mgmt
  • Vancomycin + cefotaxime or ceftriaxone, if > 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
antibiotic use in pneumococcal meningitis
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
vancomycin use in pneumococcal meningitis
Vancomycin use inpneumococcal meningitis
  • Combination therapy since late 90’s
  • 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
vancomycin use in pneumococcal meningitis1
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)

other antibiotics in pneumococcal 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

Other antibiotics inpneumococcal meningitis (resistant)
dexamethasone use in meningitis
Dexamethasone use in meningitis
  • Consider if H flu & S pneumo meningitis & > 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
pneumococcal meningitis treatment
Pneumococcal meningitis - Treatment
  • LP after 24-48 hours to evaluate therapy if:
    • Received dexamethasone
    • PCN-non-susceptible
    • MIC’s not available
    • Child’s condition not improving
infection control precautions invasive pneumococcus
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
meningococcal meningitis
Meningococcal meningitis
  • Neisseria meningitidis
  • ~10 - 15% with chronic throat carriage
  • Outbreaks in households, high schools, dorms
    • Accounts for <5% of cases
  • 2,400 - 3,000 cases occur in the USA each year
  • Peaks <2 years of age & 15-24 years
meningococcal disease
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
meningococcemia isolation
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 <4 days
meningococcemia treatment
Meningococcemia - Treatment
  • Antibitotic resistance rare
  • Antibitotics:
    • PCN
    • Cefotaxime or Ceftriaxone
  • Patient should get rifampin prior to discharge
meningococcal disease care takers
Meningococcal disease - Care takers
  • Day care where child attends >25 h/wk, kids are >2 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)

meningococcemia prophylaxis
Meningococcemia - Prophylaxis
  • No randomized controlled trials of effectiveness
  • Treat within 24 hours of exposure
  • Vaccinate affected population, if outbreak
meningococcemia prophylaxis1
Meningococcemia - Prophylaxis
  • Rifampin
    • Urine, tears, soft contact lenses orange; OCP’s ineffective
    • <1 mo 5 mg/kg PO Q 12 x 2 days
    • >1 mo 10 mg/kg (max 600 mg) PO Q 12 x 2 days
  • Ceftriaxone
    • 12 y 125 mg IM x 1 dose
    • >12 y 250 mg IM x 1 dose
  • Ciprofloxacin
    • 18 y 500 mg PO x 1 dose
meningococcal meningitis outcomes
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
tb meningitis
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
aseptic vs partially treated bacterial meningitis
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
viral meningitis
Viral meningitis
  • Summer, fall
  • Severe headache
  • Vomiting
  • Fever
  • Stiff neck
  • CSF - pleocytosis (monos), NL protein, NL glucose
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

Etiology viral meningitis
other causes of aseptic meningitis
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
viral meningitis treatment
Viral meningitis - Treatment
  • Supportive
  • No antibiotics
  • Analgesia
  • Fever control
  • Often feel better after LP
  • No isolation - Standard precautions
viral meningitis outcomes
Viral meningitis - Outcomes
  • Adverse outcomes rare
  • Infants <1 year have higher incidence of speech & language delay
meningoencephalitis etiology
Meningoencephalitis - etiology
  • Herpes simplex type 1
  • Rabies
  • Arthropod-borne
    • St. Louis encephalitis
    • La Crosse encephalitis
    • Eastern equine encephalitis
    • Western equine encephalitis
    • West Nile
herpes simplex 1 encephalitis
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
west nile virus
West Nile Virus
  • Via bite of infected mosquito
  • Incubation period 3 - 14 days
  • 1 in 150 infected persons get encephalitis
    • 4% of those are <20 years of age
  • H/A, fever, neck stiffness, stupor, coma, convulsions, weakness, & paralysis
  • Supportive therapy
  • Mortality 9%
west nile virus1
West Nile Virus

MMWR Dec 2002 51;1129-33

summary
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