Transcript Diagnosis

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
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)
Clinical signs of meningeal irritation
Diagnosis – lumbar puncture
• Contraindications:
 Respiratory distress (positioning)
  ICP reported to increase risk of herniation
 Cellulitis at area of tap
 Bleeding disorder
CSF evaluation
Condition
Normal
Bacterial,
acute
Bacterial,
part rx’d
TB
Fungal
Viral
WBC
Protein Glucose
(mg/dL) (mg/dL)
<7, lymphs mainly 5-45
>50
100 – 60K PMN’s
100-500 Low
1 – 10,000
Low to
100+
normal
100-500 <50
25-500 <50
50-100 Normal
10 – 500
25 – 500
<1000
CSF Gram stain
Hemophilus influenza
(H flu)
Strep pneumoniae
Not addressed
• Indwelling CNS catheters
• S/P cranial surgery
• Anatomic defects predisposing to meningitis
• Immunocompromised patients
• Abscesses
Bacterial meningitis
• 3 - 8 month olds at highest risk
• 66% of cases occur in children <5 years old
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
• Fever
• Malaise
• Vomiting
• Alteration in mental status
• Shock
• Disseminated intravascular coagulation (DIC)
• Cerebral edema
 Vital signs
 Level of mentation
Increased intracranial pressure (ICP)
• Papilledema
• Cushing’s triad
 Bradycardia
 Hypertension
 Irregular respiration
• ICP monitor (not
routine)
• Changes in pupils
 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
• 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
• Neonates: 14 – 21 days
• Gram negative meningitis: 21 days
• Pneumococcal, H flu: 10 days
• Meningococcal: 7 days
Bacterial Meningitis - Treatment
Neonatal (<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
• Hydrocephalus
• Subdural effusion or
empyema ~30%
• Stroke
• Abscess
• Dural sinus
thrombophlebitis
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
• Strep pneumoniae
• Neisseria meningitidis
• TB
• Hemophilus influenza
Pneumococcal meningitis
Antibiotic susceptibility
• Susceptible
• Non-susceptible
• Resistant
Pneumococcal resistance
• Strep pneumococcus - most common cause of
invasive bacterial infections in children >2
months old
• Incidence of PCN-, cefotaxime- & ceftriaxonenonsusceptible 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
• 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
• Vancomycin + cefotaxime or ceftriaxone, if > 1
month old
• If hypersensitive (allergic) to -lactam
antibiotics, use vancomycin + rifampin
• D/C vancomycin once testing shows PCNsusceptibility
• Consider adding rifampin if susceptible &
condition not improving, or cefotaxime or
ceftriaxone MIC high
• Not vancomycin alone
Antibiotic use in
Pneumococcal 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
• 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 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)
• Meropenem
• Rifampin
 Carbapenem
 20 mg/kg/day  Q 12
 120 mg/kg/day  Q 8 h
 Not a solo agent
  seizure incidence, 
not generally used in
meningitis
 Slowly bactericidal
 Resistance reported
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
• 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)
• 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
• 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
• 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 - Petechiae
Meningococcemia - Purpura fulminans
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
• Antibitotic resistance rare
• Antibitotics:
 PCN
 Cefotaxime or Ceftriaxone
• Patient should get rifampin prior to discharge
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
• No randomized controlled trials of
effectiveness
• Treat within 24 hours of exposure
• Vaccinate affected population, if outbreak
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
• 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
• 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 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
• Summer, fall
• Severe headache
• Vomiting
• Fever
• Stiff neck
• CSF - pleocytosis (monos), NL protein, NL
glucose
Etiology viral meningitis
• Enteroviruses
predominate
• Less common:
 Mumps
 Spring, summer
 HIV
 Oral-fecal route
 Lymphocytic
choriomeningitis
 ± initial GI
symptoms
 Meningitic
symptoms appear
7-10 days after
exposure
 HSV-2
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
• Supportive
• No antibiotics
• Analgesia
• Fever control
• Often feel better after LP
• No isolation - Standard precautions
Viral meningitis - Outcomes
• Adverse outcomes rare
• Infants <1 year have higher incidence of speech
& language delay
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
• 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
• 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 Virus
MMWR Dec 2002 51;1129-33
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