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Meningitis

This article discusses the etiology, diagnosis, and treatment of meningitis outside of the neonatal period. It explores current controversies, such as the use of steroids and the need for admission/ICU. Relevant for pediatrics and infectious disease.

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Meningitis

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  1. Meningitis Steven Spencer Peds ID

  2. Objectives • Discuss etiology, diagnosis and treatment of meningitis outside of the neonatal period • Will not discuss viral encephalitis, fungal disease or CSF shunt infections • Discuss current controversies • Steroids? • Need for admission/Need for ICU • Deployment specific considerations

  3. Definition • 4 potential anatomic spaces defined by meninges • dura mater and bone (epidural abscess) • dura mater and arachnoid (subdural empyema) • arachnoid and pia mater (meningitis) • below pia mater (intra-cranial infection)

  4. Definition • Inflammation of the meninges (pia and arachnoid mater) • When accompanied by parenchymal involvement, referred to as meningoencephalitis

  5. Pathogenesis • Mucosal colonization • 25% of healthy people acquire new strains of pneumococcus each year • 6% acquire new strains of meningococcus • 20% of adults transiently colonized with H. influenzae after case contact • Bacteremia

  6. Pathogenesis • Invasion • Why? • Most bacteremias do not result in meningitis • ?Role of polysaccharide capsule • Only certain capsular types of pneumococci, meningococci, H. influenzae, E. coli and GBS have a predilection to cause meningitis • Subarachnoid space inflammation

  7. Classification • Acute meningitis • Aseptic: negative screening cultures and stains • May still be bacterial such as Syphillis or Lyme • Septic: bacterial infection • Recurrent meningitis • at least 2 and often multiple distinct episodes • Chronic meningitis • meningitis that persists for 4 or more weeks

  8. Bacterial Meningitis • Changing epidemiology • 1986: 12,960 cases • H. flu responsible for 1/2 cases, and 70% in children (most aged 1month to 3 years) • 1/200 children with invasive H. flu by age 5 • 1995: 5,755 cases • 1985-1991: 82% reduction in H. influenzae • 1st Hib in 1985- not very good • Protein conjugate in late 1987 • mean age shifted from 15 months to 25 years • Hib now decreased by 99% • <1 case/100,000 kids under the age of 5

  9. Bacterial Meningitis • Pneumococcus became #1 • Prevnar vaccine licensed in 2000 • Targets 7 strains most commonly causing invasive disease– 75 to 90% reduction in meningitis • Same strains are also the ones most commonly Pen resistant or MDRSP • Menactra vaccine • Too soon to tell for actual outcomes • But 96% will produce protective antibodies

  10. Age neonate, infant, elderly Sex male:female=1.7:1 Race African-American Socioeconomic crowding, military recruits Immunosuppression antibody deficiency, complement deficiency, asplenia, leukopenia Chronic disease alcoholism, diabetes, cirrhosis (GBS) Risk Factors

  11. Bacteria Note- E. coli not represented in neonates

  12. Case Fatality Rate According to Organism Note– morbidity such as hearing loss, MR, CP etc MUCH higher

  13. Clinical Findings • 3 basic patterns of illness • Most common is an insidious presentation with non-specific symptoms (fever, n/v, malaise) that progresses over several days (3-5) before meningitis is diagnosed • Small number have fulminate course • Small number with non-fulminate course that progresses over 1-2 days

  14. Clinical Findings

  15. Clinical Findings • Headache >90% • Fever >90% • Meningismus >85% • AMS >80% • Vomiting ~30% • Seizures ~30% • Kernig’s/Brudzinki’s ~50% • Unreliable under ~12 months • Look for tense, bulging, pulsitile fontanelle

  16. Clinical Findings • Kernig’s sign • flexion of patient’s hip 90 degrees, then extending the knee causes pain • Brudzinki’s sign • flexion of patient’s neck causes flexion of hip and knee

  17. Clinical Findings • Petechiae/purpura ~30% • Focal neuro findings ~25% • Ocular palsies ~10% • Hemiparesis <5% • Myalgias ~20% • Papilledema <1%

  18. Diagnosis • Lumbar puncture • neuroimaging first if suspect intracranial mass lesion, a severely depressed sensorium or papilledema • if imaging performed, give empiric antibiotics prior to imaging • If no LP at remote clinic, give antibiotics prior to transport

  19. Diagnosis • Cell Count and Differential • cytocentrifugation of CSF • If WBC less than 5, ignore the differential • Otherwise, the presence of > 10% PMNs suggests bacterial infection • The younger the child, the less reliable this is

  20. CSF labs • Glucose- in bacterial meningitis often <50% of serum value • Protein- may be elevated (>50) • Bloody tap ruins both of these values

  21. The Bloody Tap • Don’t ask me, you should have gotten it right the first time

  22. The Bloody Tap • No right answer • Results can vary based amount of blood in amount of CSF, what is the HCT, what is the peripheral WBC count etc. Some use CBC to CSF ratios. • Sometimes seems like too many WBC’s or seems OK- it is merely a hint • Sometimes just need to re-tap

  23. Effect of Antibiotics on LP • With appropriate IV antibiotics, culture and gram stain should become negative in 24 hours • CSF glucose approaches normal levels in 80% of patients within 3 days • At one week, the cell count is still increased in 50% of patients • Protein level remains elevated for 10 days or more

  24. Diagnosis • Gram Stain • 57% adults with bacterial meningitis positive (Arch Intern Med 1997;157:425) • 90% infants with pneumococcal meningitis positive (Pediatrics 1998;102:538) • 50% yield with gram-negative or post-neurosurgery

  25. N. meningitidis

  26. S. pneumoniae

  27. L. monocytogenes

  28. Diagnosis • Rapid antigen detection assay • results rarely altered therapy • false-positives>true positives, especially urinary test • Example- Some E. coli cross reacts with GC • BUT may be useful for partially treated • Never! Never! Never! use urinary antigens in kids • PCR • under development for bacterial meningitis • viral assays commercially available • HSV, enterovirus

  29. DiagnosisSummary Glucose <34 mg/dL, CSF:serum glucose < .23, WBC > 2,000 or PMN count > 1180=predictive value of 99% for bacterial meningitis (JAMA 1989;262:2700)

  30. Treatment • General guidelines • CSF is an area of impaired host resistance • specific antibody and complement are absent or low in both normal and purulent CSF • opsonic and bactericidal activity generally low or undetectable in purulent CSF • inefficient phagocytosis resulting in rapid bacterial multiplication

  31. Treatment • Need bactericidal antibiotics • Poorer outcome with bacteriostatic antibiotics • Need good penetration, adequate concentration in CSF and intrinsic activity in infected fluid • In animal models, need 10-30x MBC

  32. % Penetration Into CSF with Meningitis Infect Dis Clin NA 00;14:45

  33. Specific PathogensS. pneumoniae • Still the most common • Scenario • A blood culture grows out Pneumococcus that is reported to be ceftriaxone sensitive • CSF cx from the same patient grows Pneumococcus that is reported as resistant • Which report is correct? NEJM 1995;333:481

  34. Answer

  35. Answer • BOTH!!! • Pneumococcus has two sets of MIC’s • Antibiotics get decreased penetration into CSF

  36. S. pneumoniae • Beta-lactams for penicillin-susceptible strains • Always add vanc if GPC’s seen on grams stain • Vanc/ceftriaxone synergistic even against strains for which the MIC of ceftriaxone was high • No need for prophylaxis of contacts

  37. N. meningitidis • 8 major serogroups • B,C,Y and W-135 responsible for most disease in kids in developed countries • A/C cause most epidemics • Classically associated with a rash

  38. N. meningitidis • Vaccination for N. meningitidis • Current vaccine is quadrivalent containing polysaccharides of groups A,C,Y and W-135 • No vaccine currently available for group B • Recommended to travelers going to highly endemic areas (e.g.. West Africa) • Menactra for all kids 11 and older

  39. N. meningitidis

  40. N. meningitidis

  41. N. meningitidis

  42. N. meningitidis-Deployment Specific • Even in the tropics, pneumococcus is more common than N. meningitidis • Exception is sub-Saharan Africa (“the meningitis belt”) • Major epidemics every 5-10 years • Reports of 1,000 cases at one hospital in a single day • Usually in the middle of the dry season, and end with the onset of the rains

  43. The Meningitis Belt

  44. N. meningitidis • Wimpy, wimpy, clears rapidly with Beta-lactams • Prophylaxis for N. meningitidis • Household contacts, day-care center contacts and those with exposure to oral secretions • Transmitted by respiratory droplets • Rifampin 600 mg q12 for 2 days • Cipro 500 mg po once • Ceftriaxone 250 IM once

  45. Md. Hopes To Prevent Meningitis By Amy ArgetsingerWashington Post Staff WriterFriday, August 25, 2000; Page B01 Jesse Gardiner was the picture of health when his parents came to visit him on a winter Friday last year--a robust 18-year-old enjoying his freshman year at Frostburg State University. The next day he called home with a headache, which by Sunday evening was settling in like the flu--nothing serious, it seemed. But by Monday morning, he was too weak to walk. By the time his parents made the drive from their Frederick home to Cumberland, Md., he was in the hospital, unable to stand on his own.

  46. Empiric Therapy • Age<3mo: ampicillin plus cefotaxime/ceftriaxone (GBS, E. coli, Listeria) • Age 3mo-18yr: cefotaxime/ceftriaxone+vanc (N. meningitidis, S. pneumo, H. flu) • Age 18yr-50yr: cefotaxime/ceftriaxone+vanc (S. pneumo, N. meningitidis) • Age >50yr: Ampicillin+ceftriaxone+vanc (S. pneumo, Listeria, GNRs)

  47. Empiric Therapy • With impaired cellular immunity: ampicillin/ceftazidime/vanc (Listeria or GNRs) • With head trauma, neurosurgery or CSF shunt: vanc/ceftazidime (Staphylococci, GNRs, S. pneumo) NEJM 1997;336:708

  48. Steroids? • Rationale: decrease meningeal inflammation, intracranial hypertension and cerebral edema • 4 prospective, placebo-controlled, randomized trials in children > 2 mos: adjunctive dexamethasone substantially reduced audiologic and neurologic sequelae (NEJM 1992;327:864) • Almost all had Hib, no real benefit seen with pneumococcus

  49. Steroids • Influence of dexamethasone on antimicrobial penetration into CSF during experimental pneumococcal meningitis (rabbitmodel) % penetration Drug w/o dex w/dex Ceftriaxone 13.8 7.9 Vancomycin 53.1 39.3 Rifampin 4.3 5.4 Antimicrob Agents Chemother 1994;338:1320-1324

  50. Steroids-Conclusions • Children more than 2 months old with H. influenzae • Adults with PCN-sensitive S. pneumo meningitis • Adult docs/ER’s give OFTEN • ?Adults with other types of meningitis • MUST be given before or at ~same time as antibiotics • Several studies included for your review– we will skip ahead

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