up to date about meningitis

1. Meningitis and Encephalitis:
Diagnosis and Treatment Update
Dr Mohamed Abu nada
Pediatric neurology department
Dr. Al Rantisi Specialized children
hospital

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

4. 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)

5. Bulging fontanel

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

12. CSF Gram stain
Hemophilus influenza Strep pneumoniae
(H flu)

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

15. Suppurative (purulent ) meningitis
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 2 February 2007 04:53 PM)
© 2007 Elsevier

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

17. Bacterial meningitis –
Clinical course
 Fever
 Malaise
 Vomiting
 Alteration in mental status
 Shock
 Disseminated intravascular coagulation
(DIC)
 Cerebral edema

18. Increased intracranial
pressure (ICP)
Papilledema
Cushing’s triad
o Bradycardia
o Hypertension
o Irregular respiration
Changes in pupils

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

21. Meningitis - Treatment
duration
Neonates: 14 – 21 days
Gram negative meningitis: 21 days
Pneumococcal, H flu: 10 days
Meningococcal: 7 days

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

23. Meningitis - Acute
complications
 Hydrocephalus
 Subdural effusion or
empyema ~30%
 Stroke
 Abscess
 Dural sinus
thrombophlebitis

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

26. Complications and
Sequelae
 Complications:  Sequelae:
 Shock/Sepsis  Deafness
 Cerebral edema  Developmental delay,
 Subdural empyema cognitive impairments
 Subdural effusion  Chronic seizure disorder
 Ventriculitis  Hydrocephalus
 Abscess
 Seizures

27. Bacterial meningitis -
children
Strep pneumoniae
Neisseria meningitidis
Hemophilus influenza

28. Pneumococcal meningitis

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

41. 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 Latex agglutination
Petechial scrapings

42. Meningococcemia -
Petechiae

43. Meningococcemia - Purpura
fulminans

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

47. Meningococcemia -
Treatment
 Antibitotic resistance rare
 Antibitotics:
PCN
Cefotaxime or Ceftriaxone
Patient should get rifampin prior to
discharge

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

54. Aseptic Meningitis
 Other Viral
 HIV
 Lymphocytic choriomeningitis virus
 Arbovirus
 Mumps
 CMV
 EBV
 VZV
 Adenovirus
 Measles
 Rubella
 Rotavirus
 Influenza and parainfluenza

55. Aseptic Meningitis
 Other infectious
Borrelia burgdorferi
Mycobacterium tuberculosis
Treponema pallidum
Mycoplasma pneumoniae
Rickettsia, erlichia, brucella
Chlamydia

56. Aseptic Meningitis
 Fungal
Cryptococcus
Coccidiodes
Histoplasmosis
 Parasitic
Angiostrongylus
Toxoplamosis

57. Aseptic Meningitis
 Medication
– NSAID’s
– Bactrim
– Pyridium
 Malignancy
– Lymphoma and leukemia
– Metastatic carcinoma
 Autoimmune
– Sarcoid
– Behcet’s
– SLE

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

59. Viral meningitis
Summer, fall
Severe headache
Vomiting
Fever
Stiff neck
CSF - pleocytosis (monos), NL
protein, NL glucose

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