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Meningitis

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Meningitis

  1. 1. Meningitis and Encephalitis:Diagnosis and Treatment Update Dr Mohamed Abu nada Pediatric neurology department Dr. Al Rantisi Specialized children hospital
  2. 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. 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. 4. Bulging fontanel
  5. 5. Clinical signs of meningeal irritationBrudzinski neck sign pt lies supine, head is passively elevatedby examiner, involuntary flexion of knees
  6. 6. Kernig sign pt lies supine with knees flexed, knees extended,complain of pain in back or neck
  7. 7. 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
  8. 8. Contraindications:  Respiratory distress (positioning)  ↑ ICP reported to increase risk of herniation  Cellulitis at area of tap  Bleeding disorder
  9. 9. 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 (orBacterial, acute 300–2,000; Neutros <50% serum 500 predominate glucose)Bacterial, part usually Low to 5 – 10,000rx’d 100-500 normalTB 10 – 500 100-3000 <50Viral or Usually Generally normal;Meningoenceph rarely >1000 50-200 may be decreasedalitis
  10. 10. CSF Findings in Infants and Children Component Normal Normal Newborn Bacterial Viral Meningitis Children MeningitisLeukocytes/mc 0-6 0-30 >1000 100-500LWBCNeutrophils 0 2-3 80-95 < 40(%)Glucose 40-80 32-121 <40 < 30 - 70(mg/dL) 0.6 <0.4 CSF:serum CSF:serumProtein 20-30 19-149 >100 50-100(mg/dL)Erythrocytes/ 0-2 0-2 0-10 0-2mcL
  11. 11. CSF Gram stainHemophilus influenza Strep pneumoniae (H flu)
  12. 12. Bacterial meningitis 3 - 8 month olds at highest risk 66% of cases occur in children <5 years old
  13. 13. 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
  14. 14. Suppurative (purulent ) meningitis Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 2 February 2007 04:53 PM) © 2007 Elsevier
  15. 15. 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
  16. 16. Bacterial meningitis –Clinical course Fever Malaise Vomiting Alteration in mental status Shock Disseminated intravascular coagulation (DIC) Cerebral edema
  17. 17. Increased intracranialpressure (ICP)PapilledemaCushing’s triad o Bradycardia o Hypertension o Irregular respirationChanges in pupils
  18. 18. Meningitis- Empiric AntibioticChoices  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
  19. 19. 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
  20. 20. Meningitis - TreatmentdurationNeonates: 14 – 21 daysGram negative meningitis: 21 daysPneumococcal, H flu: 10 daysMeningococcal: 7 days
  21. 21. 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
  22. 22. Meningitis - Acutecomplications  Hydrocephalus  Subdural effusion or empyema ~30%  Stroke  Abscess  Dural sinus thrombophlebitis
  23. 23. 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%
  24. 24. Long-term Neurological Complications Adverse Outcomes at One Year of Age of 12 Infants With Bacterial Meningitis Category of Disability NumberDevelopment delay 10Cerebral palsy 1Microcephaly 3Hemiparesis 3Hearing loss 1Blindness 2Seizure disorder 3Total number of disabilities exceeds the number of infants owing to the presence of multipledisabilities in most subjects Klinger G, et al. Pediatrics. 2000;106:477-482
  25. 25. Complications andSequelae Complications:  Sequelae: Shock/Sepsis  Deafness Cerebral edema  Developmental delay, Subdural empyema cognitive impairments Subdural effusion  Chronic seizure disorder Ventriculitis  Hydrocephalus Abscess Seizures
  26. 26. Bacterial meningitis -children Strep pneumoniae Neisseria meningitidis Hemophilus influenza
  27. 27. Pneumococcal meningitis
  28. 28. 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
  29. 29. 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
  30. 30. 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
  31. 31. 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
  32. 32. 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 min after completion of a 30-min infusion (35-40 mcg/mL)
  33. 33. Other antibiotics inpneumococcal 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
  34. 34. 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
  35. 35. When Do We UseSteroids? 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).
  36. 36. 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.
  37. 37. Pneumococcal meningitis -Treatment LP after 24-48 hours to evaluate therapy if: Received dexamethasone PCN-non-susceptible Child’s condition not improving
  38. 38. Infection controlprecautions(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
  39. 39. 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
  40. 40. 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
  41. 41. Meningococcemia -Petechiae
  42. 42. Meningococcemia - Purpurafulminans
  43. 43. 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
  44. 44. Meningococcemia -Treatment Antibitotic resistance rare Antibitotics: PCN Cefotaxime or CeftriaxonePatient should get rifampin prior to discharge
  45. 45. Meningococcemia - Prophylaxis No randomized controlled trials of effectiveness Treat within 24 hours of exposure Vaccinate affected population, if outbreak
  46. 46. 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
  47. 47. 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
  48. 48. 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
  49. 49. 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
  50. 50. 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
  51. 51. Aseptic Meningitis Other Viral  HIV  Lymphocytic choriomeningitis virus  Arbovirus  Mumps  CMV  EBV  VZV  Adenovirus  Measles  Rubella  Rotavirus  Influenza and parainfluenza
  52. 52. Aseptic Meningitis Other infectious Borrelia burgdorferi Mycobacterium tuberculosis Treponema pallidum Mycoplasma pneumoniae Rickettsia, erlichia, brucella Chlamydia
  53. 53. Aseptic Meningitis Fungal Cryptococcus Coccidiodes Histoplasmosis Parasitic Angiostrongylus Toxoplamosis
  54. 54. Aseptic Meningitis Medication – NSAID’s – Bactrim – Pyridium Malignancy – Lymphoma and leukemia – Metastatic carcinoma Autoimmune – Sarcoid – Behcet’s – SLE
  55. 55. Aseptic vs. partially treatedbacterial 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
  56. 56. Viral meningitisSummer, fallSevere headacheVomitingFeverStiff neckCSF - pleocytosis (monos), NL protein, NL glucose
  57. 57. 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
  58. 58. 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
  59. 59. Viral meningitis -Treatment Supportive No antibiotics Analgesia Fever control Often feel better after LP No isolation - Standard precautions
  60. 60. Viral meningitis -Outcomes  Adverse outcomes rare  Infants <1 year have higher incidence of speech & language delay
  61. 61. 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
  62. 62. 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
  63. 63. 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

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