1. Meningitis and Encephalitis:
Diagnosis and Treatment Update

2. 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
Meningitis:
bacterial
viral
fungal
aseptic (Lyme, syphillis) TB
Other causes of aseptic meningitis:
malignancy
NSAID’s
chemo
abx

3. Symptoms of meningitis
Fever
Altered consciousness, irritability, photophobia
Vomiting, poor appetite
Seizures %
Bulging fontanel 30%
Stiff neck or nuchal rigidity
Meningismus (stiff neck + Brudzinski + Kernig signs)
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 1st 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.

4. Clinical signs of meningeal irritation
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

5. Diagnosis – lumbar puncture
Contraindications:
Respiratory distress (positioning)
 ICP reported to increase risk of herniation
Cellulitis at area of tap
Bleeding disorder
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, 6th nerve palsy, Cushing’s triad (HTN, brady, irreg resp) or pappilledema
GIVE abx anyway

6. CSF evaluation Condition WBC Protein (mg/dL) Glucose (mg/dL) Normal
<7, lymphs mainly
5-45
>50
Bacterial, acute
100 – 60K PMN’s
Low
Bacterial, part rx’d
1 – 10,000
100+
Low to normal TB
10 – 500
<50
Fungal
25 – 500
25-500
Viral
<1000
50-100
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.

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

8. Not addressed Indwelling CNS catheters S/P cranial surgery
Anatomic defects predisposing to meningitis
Immunocompromised patients
Abscesses

9. Bacterial meningitis 3 - 8 month olds at highest risk
66% of cases occur in children <5 years old
Highest attack rate 3-8 mos old

10. 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

11. Bacterial meningitis – Clinical course
Fever
Malaise
Vomiting
Alteration in mental status
Shock
Disseminated intravascular coagulation (DIC)
Cerebral edema
Vital signs
Level of mentation
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

12. Increased intracranial pressure (ICP)
Papilledema
Cushing’s triad
Bradycardia
Hypertension
Irregular respiration
ICP monitor (not routine)
Changes in pupils

13.  ICP treatment Elevate HOB 30o 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 PaCO torr
Elevate HOB 30o

14. 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
SIADH – presence of hyponatremia with low serum Na, low osmolality, high urine Na excretion

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

16. 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

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

18. 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 %
Neurologic abnormalities include:
cranial nerve dysfunction
paresis
hyper/hypotonia
ataxia
seizure disorder
blindness
language delay
mental retardation
behavioral problems

19. Bacterial meningitis - children
Strep pneumoniae
Neisseria meningitidis TB
Hemophilus influenza

20. Pneumococcal meningitis

21. Antibiotic susceptibility
Susceptible
Non-susceptible
Resistant

22. 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
Resistant organisms do NOT cause more sggressive disease

23. 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

24. 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
Add Vancomycin for neonate, if CSF suspicious of pneumococcus

25. Antibiotic use in Pneumococcal meningitis
PCN-susceptible organism:
PenG 250, ,000 U/kg/day  Q h
Ceftriaxone 100 mg/kg/day  Q h
Cefotaxime mg/kg/day  Q 8 h
Chloramphenicol mg/kg/day  Q 6 h
Adequate cephalosporin levels in CSF ~2.8 hours after dose administration

26. 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

27. 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 minutes after completion of a 30-minute infusion
(35-40 mcg/mL)

28. Other antibiotics in pneumococcal meningitis (resistant)
Meropenem
Carbapenem
120 mg/kg/day  Q 8 h
 seizure incidence,  not generally used in meningitis
Resistance reported
Rifampin
20 mg/kg/day  Q 12
Not a solo agent
Slowly bactericidal

29. Dexamethasone use in meningitis
Consider if H flu & S pneumo meningitis & > 6 wks old 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
Conflicting results of small studies
May decrease fever, giving false impression of improvement

30. Pneumococcal meningitis - Treatment
LP after hours to evaluate therapy if:
Received dexamethasone
PCN-non-susceptible
MIC’s not available
Child’s condition not improving

31. 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

32. Meningococcal meningitis
Neisseria meningitidis
~ % with chronic throat carriage
Outbreaks in households, high schools, dorms
Accounts for <5% of cases
2, ,000 cases occur in the USA each year
Peaks <2 years of age & years
Risk of transmission greatest in 1st week of exposure
1 per 100,000 people

33. 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

34. Meningococcemia - Petechiae

35. Meningococcemia - Purpura fulminans

36. 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 days, usually <4 days

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

38. 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” – x risk
(kissing, eating/ drinking utensils, mouth-to-mouth, suctioning, intubating)
No randomized controlled trials of the effects of prophylaxis among contacts
Abx eradicate throat carriage
No evidence that doing this reduces the risk of meningococcal disease

39. Meningococcemia - Prophylaxis
No randomized controlled trials of effectiveness
Treat within 24 hours of exposure
Vaccinate affected population, if outbreak

40. 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

41. 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

42. 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

43. Aseptic vs. partially treated bacterial meningitis
Aseptic much more common
Gram stain positive CSF:
% in young patients
% positive in older children
If CSF fails to show organisms in a pretreated patient, then very unlikely that organism is resistant
Aseptic much more common (6-10 cases for each case of pneumococcal meningitis)
Children with aseptic meningitis should not receive vancomycin
If pretreated,

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

45. 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
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
3rd most common cause of aseptic meningitis
Genital lesions
sexual history
No treatment necessary (unlike HSV1)

46. 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
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

47. Viral meningitis - Treatment
Supportive
No antibiotics
Analgesia
Fever control
Often feel better after LP
No isolation - Standard precautions
Not clear why sometimes feel better after diagnostic LP

48. Viral meningitis - Outcomes
Adverse outcomes rare
Infants <1 year have higher incidence of speech & language delay

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

50. 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
Polymerase chain reaction to herpes DNA

51. West Nile Virus Via bite of infected mosquito
Incubation period 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%

52. West Nile Virus
MMWR Dec ;

53. 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