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Meningitis
1. Meningitis and Encephalitis:
Diagnosis and Treatment Update
Dr Mohamed Abu nada
Pediatric neurology department
Dr. Al Rantisi Specialized children
hospital
2.
3. 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
6. Clinical signs of meningeal irritation
Brudzinski neck sign pt lies supine, head is passively elevated
by examiner, involuntary flexion of knees
7. Kernig sign pt lies supine with knees flexed, knees extended,
complain of pain in back or neck
8. Diagnosis – lumbar puncture
CSF studies
Tube 1: gram stain and cx
Tube 2: glucose, protein
Tube 3: cell count and differential
Tube 4: hold in lab
9. Contraindications:
Respiratory distress (positioning)
↑ ICP reported to increase risk of
herniation
Cellulitis at area of tap
Bleeding disorder
10. CSF evaluation
Protein Glucose
Condition WBC
(mg/dL) (mg/dL)
>50 (or 75%
Normal <5, ≥75% lymphos 20–45 serum glucose)
100–10,000 or more; usually Decreased,
usually 100– usually <40 (or
Bacterial, acute 300–2,000; Neutros <50% serum
500
predominate glucose)
Bacterial, part usually Low to
5 – 10,000
rx’d 100-500 normal
TB 10 – 500 100-3000 <50
Viral or Usually Generally normal;
Meningoenceph rarely >1000 50-200 may be decreased
alitis
11. CSF Findings in Infants and
Children
Component Normal Normal Newborn Bacterial Viral Meningitis
Children Meningitis
Leukocytes/mc 0-6 0-30 >1000 100-500
L
WBC
Neutrophils 0 2-3 80-95 < 40
(%)
Glucose 40-80 32-121 <40 < 30 - 70
(mg/dL) 0.6 <0.4
CSF:serum CSF:serum
Protein 20-30 19-149 >100 50-100
(mg/dL)
Erythrocytes/ 0-2 0-2 0-10 0-2
mcL
13. Bacterial meningitis
3 - 8 month olds at highest risk
66% of cases occur in children
<5 years old
14. 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,
H. influenzae
16. Pathogens- Special Situations
There are certain situations which
predispose children to particular pathogens
VP shunts/penetrating head trauma- Staph epi
Neural tube defects- Staph aureus, enteric
organisms
T-cell defects (HIV)- cryptococcus, listeria
Sinus fracture- Strep pneumo
Asplenia (HgB SS)- Neisseria, H. flu, S. pneumo
Terminal Complement deficiency- Neisseria
19. Meningitis- Empiric Antibiotic
Choices
Quick initiation of antibiotics is a must
Supportive care only for aseptic meningitis
– HSV is the only exception
Less than 1 month
– Ampicillin AND Cefotaxime
Ampicillin-covers GBS and Listeria
Cefotaxime-gram negatives including e.coli
Amp/Gent also acceptable regimen
Greater than 1 month
– Cefotaxime or Ceftriaxone AND Vancomycin
3rd generation cephalosporin will cover susceptible S.
pneumo, Neisseria, and H. Flu
Vancomycin covers resistant S. pneumo, MSSA, MRSA
Need to use higher doses to allow penetration of the
blood-brain barrier
20. Meningitis-Treatment
Supportive Care
– Fluids, treatment for shock and/or DIC, neuro checks
Steroids
Steroids thought to blunt effects of host inflammatory
response
Theoretical concern of steroids reducing permeability
of blood brain barrier to antibiotics
Most benefit seen with S. pneumo and H. flu
Consider repeat LP 24-36 hours after initiating
treatment to assure sterilization of CSF if
resistant organism or poor response to
treatment
22. 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
24. 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%
25. Long-term Neurological
Complications
Adverse Outcomes at One Year of Age of 12 Infants
With Bacterial Meningitis
Category of Disability Number
Development delay 10
Cerebral palsy 1
Microcephaly 3
Hemiparesis 3
Hearing loss 1
Blindness 2
Seizure disorder 3
Total number of disabilities exceeds the number of infants owing to the presence of multiple
disabilities in most subjects
Klinger G, et al. Pediatrics. 2000;106:477-482
29. 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 β-lactam antibiotics often
resistant to trimethoprim-
sulfamethoxazole, erythromycin,
chloramphenicol, tetracycline
30. Pneumococcal meningitis
– Mgmt
Vancomycin + cefotaxime or ceftriaxone,
if > 1 month old
If hypersensitive (allergic) to β-lactam
antibiotics, use vancomycin + rifampin
D/C vancomycin once testing shows PCN-
susceptibility
Consider adding rifampin if susceptible &
condition not improving
Not vancomycin alone
31. 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
32. 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
33. 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 min after
completion of a 30-min infusion
(35-40 mcg/mL)
34. Other antibiotics in
pneumococcal meningitis
(resistant) Rifampin
Meropenem 20 mg/kg/day ÷ Q 12
Carbapenem Not a solo agent
120 mg/kg/day÷q 8 h Slowly bactericidal
↑ seizure incidence,
∴ not generally
used in meningitis
Resistance reported
35. 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-α, 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
36. When Do We Use
Steroids?
Therapy should be initiated shortly
before or at the same time as the first
dose of antibiotics, (likelihood of
unfavorable outcome was much higher
in patients in whom dexamethasone
was given after antibiotics).
37. Dosage and Duration of
Dexamethasone Therapy
Dexamethasone should be continued for 4 days if the
Gram’s stain of CSF reveals organisms consistent with
S. pneumoniae or if cultures grow S. pneumoniae.
Therapy should be discontinued if Gram’s stain and or
culture reveal another pathogen or no meningitis.
Randomized trial showed no benefit with other
pathogens (mainly meningococcus).
Recommended IV therapy doses are 0.15mg/kg every
6 hours for children, although some studies indicate as
little as two days of therapy for children.
38. Pneumococcal meningitis -
Treatment
LP after 24-48 hours to evaluate
therapy if:
Received dexamethasone
PCN-non-susceptible
Child’s condition not improving
39. 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
40. Meningococcal meningitis
Neisseria meningitidis
~10 - 15% with chronic throat carriage
Outbreaks in households, high schools.
– Accounts for <5% of cases
2,400 - 3,000 cases occur in the USA
each year
Peaks <2 years of age & 15-24 years
46. 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
48. Meningococcemia -
Prophylaxis
No randomized controlled trials of
effectiveness
Treat within 24 hours of exposure
Vaccinate affected population, if outbreak
49. Meningococcemia - Prophylaxis
Rifampin
Urine, tears, soft contact lenses orange;
<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
50. Presenting Features of Meningococcal
Infection Associated with Poor
Prognosis
Presence of petechiae > 12 hours before
admission
Presence of hypotension (systolic <70 mm
Hg)
Absence of meningitis (<20 WBC/mm3)
Peripheral white blood cell count
<10,000/mm3
Erythrocyte sedimentation rate R.et al J. Pediatr 1966
Stiehm, E.
<10 mm/hour
51. Meningococcal meningitis -
Outcomes
Substantialmorbidity: 11% - 9% of
survivors have sequelae
Neurologic disability
Limb loss
Hearing loss
10% case-fatality ratio for
meningococcal sepsis
1% mortality if meningitis alone
52. 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
53. Aseptic Meningitis
All non-bacterial causes of meningitis
Typically less ill appearing than bacterial
meningitis
Most common cause is viral
– HSV
Consider especially in infants presenting with seizure
Usually HSV type II
Treat with acyclovir
– Enterovirus (coxsackie, echovirus)
Typically occurs during late summer and fall
Spread via respiratory secretions and fecal-oral
Affects all ages
Generally self-limited illness
58. 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
IfCSF fails to show organisms in
a pretreated patient, then very
unlikely that organism is resistant
60. Etiology viral meningitis
Enteroviruses Less common:
predominate – Mumps
– Spring, summer – HIV
– Oral-fecal route – Lymphocytic
– ± initial GI choriomeningit
symptoms is
– Meningitic – HSV-2
symptoms
appear 7-10 days
61. 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
62. Viral meningitis -
Treatment
Supportive
No antibiotics
Analgesia
Fever control
Often feel better after LP
No isolation - Standard precautions
63. Viral meningitis -
Outcomes
Adverse outcomes rare
Infants <1 year have higher
incidence of speech & language
delay
64. Meningoencephalitis -
etiology
Herpes simplex type 1
Rabies
Arthropod-borne
o St. Louis encephalitis
o La Crosse encephalitis
o Eastern equine encephalitis
o Western equine encephalitis
o West Nile
65. Herpes simplex 1
encephalitis
Symptoms
o Depressed level of consciousness
o Blood tinged CSF
o Temporal lobe focus on CT scan or EEG
o + PCR
o Neonates typically will have cutaneous
vessicles
Treatment - IV acyclovir
66. Summary
Antibiotics, 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
Hinweis der Redaktion
Meningitis: bacterial viral fungal aseptic (Lyme, syphillis) TB Other causes of aseptic meningitis: malignancy NSAID’s chemo abx
Sxs appear either slowly over a few days or rapidly with sepsis Fever occurs in 50% of infants, some only fever. 15% of kids with bacterial meningitis present comatose or semi-comatose. 20-30% have seizures prior to admission or during 1 st 2 days of treatment. Uncomplicated sz (easily controlled & non-focal) may be treated during hospitalization & then meds d/c. Papilledema usually not seen at presentation. Head CT not indicated unless focal symptoms or herniation Stiffness caused by inflammation of the cervical dura and reflex spasm of the extensor muscles of the neck – uncommon in infants Lateral movement unrestricted In small child, may drop object to floor to see if they flex to follow it.
Brudzinski – pt lies supine, head is passively elevated by examiner, involuntary flexion of knees Kernig – pt lies supine with knees flexed, knees extended, complain of pain in back or neck
Needle with stylet inserted into the subarachnoid space between L3-4 or L4-5. Styleted needled used so as to not introduce a plug of epidermal cells into the space which may later grow into a cord-compressing epidermoid tumor. Contraindications: monitor sats signs of inc ICP – ptosis, anisocoria, 6 th nerve palsy, Cushing’s triad (HTN, brady, irreg resp) or pappilledema GIVE abx anyway
RBC – traumatic vs CNS bleeding. After a few hours, CSF will be xanthrochromic; if traumatic it will be clear with centrifugation. Latex agglutination has high false negative rate.
Bacterial: neutrophil predonminance,
Highest attack rate 3-8 mos old
Fever lasts 3-5 days, may go as long as 9 days in 13% of kids. Change in level of consciousness means transfer to PICU. Changes in neuro status are related to direct neuronal damage by inflammatory mediators & disruption of CBF by cerebral edema, vasculitis, thrombosis, loss of cerebral autoregulation
Recurrent fever may be associated with subdural effusion, abscess, drug fever. May warrant repeat LP. Effusions may or may not need intervention – depends on if it is increasing or causing neurologic sxs.
Cerebrovascular abnormalities Cerebral edema and increased intracranial pressure Seizures Impaired mental status Intellectual impairment Hearing loss and cranial neuropathies Subdural effusion or empyema
Resistant organisms do NOT cause more sggressive disease
Add Vancomycin for neonate, if CSF suspicious of pneumococcus
Conflicting results of small studies May decrease fever, giving false impression of improvement
Risk of transmission greatest in 1 st week of exposure 1 per 100,000 people
Especially ibuprophen
Aseptic much more common (6-10 cases for each case of pneumococcal meningitis) Children with aseptic meningitis should not receive vancomycin If pretreated,
CSF pleocytosis (mainly mononuclear cells) Normal to slightly elevated CSF protein 18% Normal to slightly low CSF glucose 12% Most not reported, so true incidence not known
Etiologic agent identified in ~20% of cases. 85% of those identified are enteroviruses. Enteroviruses: Spring, summer Oral-fecal transmission ± initial GI symptoms Arboviruses: 5% of cases Mumps: school age late winter, early spring parotitis, orchitis, pancreatitis HIV mononucleosis-like syndrome LCV lymphocytic choriomeningitis virus older kids early winter, when mice come indoors alopecia Hx exposure to rodents Herpes type 2 3 rd most common cause of aseptic meningitis Genital lesions sexual history No treatment necessary (unlike HSV1)
Leptospira young adults late summer, fall conjunctivitis, splenomegaly, jaundice, rash exposure to animal urine Lyme Sxs follow exposure by weeks to months Hx of tick exposure
Not clear why sometimes feel better after diagnostic LP