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Meningitis and Encephalitis:

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:

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  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

  3. 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)

  4. Clinical signs of meningeal irritation

  5. Diagnosis – lumbar puncture • Contraindications: • Respiratory distress (positioning) •  ICP reported to increase risk of herniation • Cellulitis at area of tap • Bleeding disorder

  6. CSF evaluation

  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

  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

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

  13.  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

  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

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

  16. 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

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

  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 2 - 29%

  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

  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

  25. 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

  26. 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

  27. 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)

  28. 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)

  29. 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

  30. 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

  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 • ~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

  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 1 - 10 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” – 300-800x risk (kissing, eating/ drinking utensils, mouth-to-mouth, suctioning, intubating)

  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: • 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

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

  45. 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

  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

  47. Viral meningitis - Treatment • Supportive • No antibiotics • Analgesia • Fever control • Often feel better after LP • No isolation - Standard precautions

  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

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