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  1. BACTERIAL MENINGITIS Gebre K. Tseggay, MD November 21, 2005

  2. MAJORCHANGESINEPIDEMIOLOGYOFMENINGITISSINCETHE1990’Smainly due to the introduction of Hib vaccine • Dramatic drop in the number of H.influenzae meningitis cases • Dramatic drop in the overall number of meningitis cases • Shift in age of distribution of bacterial meningitis (median age was 15 months in 1986, but 25 yrs in 1995) • Before the 1990’s: H. infl> S. pneumoniae> N. meningitidis • Since the 1990’s: S. pneumoniae> N. meningitidis>>>H. infl. NEJM 1997;337:970-6

  3. Etiology Of Bacterial Meningitis In The US Percentage of Total Cases Organism (1978-81) (1985) (1995) H. Influnezae 48 45 7 N. meningitidis 20 14 25 S. pneumoniae 13 18 47 Strep. agalactiae 3 6 12 Listeria m. 2 3 8 Other 8 14 - Unknown 6 -- JAMA.1985;253:1749-1754 JID.1990;162:1316-1323 NEJM.1997;337:970-976

  4. INCIDENCEOF BACTERIAL MENINGITIS IN THE USA Per 100,000 population% • S. pneumoniae 1.1 47 • N. meningitidis 0.6 25 • Group B Strep. 0.3 12 • L. monocytogenes 0.2 8 • H. influenzae 0.2 7 NEJM 1997;337:970-6

  5. CHANGES IN EPIDEMIOLOGY (cont’d) • Increase in cases of MDR- S. pneumoniae. [Resulted in changes in empiric Rx] • Clusters of cases of meningococcal meningitis in adolescents & young adults. [Resulted in change in recommendation for meningococcal vaccination] • Cochlear implants and higher risk for bacterial meningitis.[Change in recommendation for Pneumococcal +/- Hib?] • Decrease in pneumococcal invasive disease including meningitis after widespread use of of pediatric pneumococcal vaccine.


  7. ETIOLOGY OF BACTERIAL MENINGITIS BY PREDISPOSING CONDITION Immunocompromised state: S. pneumoniae, N. meningitidis, Listeria, aerobic GNR (including Ps.aeruginosa) Basilar skull fracture: S. pneumoniae, H. influenzae, beta-hemolytic strep group A. Head trauma or post-neurosurgery: S. aureus, S. epidermidis, aerobic GNR CSF shunt: S. epidermidis, S. aureus, aerobic GNR, Propionibacterium acnes

  8. PATHOGENESIS OF BACTERIAL MENINGITIS • Nasopharyngeal colonization • Direct extension of bacteria. • Parameningeal foci (sinusitis, mastoiditis, or brain abscess) • Across skull defects/fracture • From remote foci of infection (e.g., endocarditis, pneumonia, UTI…)

  9. Brain with inflammatory exudate covering the cortical hemispheres in purulent meningitis. Cohen & Powderly: Infectious Diseases, 2nd ed., Copyright © 2004 Mosby

  10. CLINICAL PRESENTATION Symptom or SignRelative Frequency (%) • FEVER>90 • HEADACHE>90 • NUCHAL RIGIDITY>85 • ALTERED MENTAL STATUS 80 • BRUDZINSKI SIGN 50 • KERNIG SIGN 50 • VOMITING ~35 • SEIZURES 10-30 • FOCAL NEURO SIGNS 10-30 • PAPILLEDEMA <1 • PHOTOPHOBIA • SKIN RASH (e.g., petechia/purpura in meningococcemia)

  11. CONFIRMATION OF SUSPECTED BACTERIAL MENINGITIS • Lumbar puncture ASAP. • If LP has to be delayed for any reason, send blood culture and start empiric antibiotics. • Who should undergo CT prior to lumbar puncture?

  12. DIAGNOSIS - CSF ExaminationTypical CSF in Patients with Bacterial Meningitis • Opening pressure 200-500 mmH2O • White blood cell count 1000-5000/mm3 • Neutrophils >80% • Protein >100 mg/dl • Glucose <40 mg/dl • CSF/serum glu ratio <0.4 • Gram stain Positive in 50-80% • Culture Positive in ~85% • Bacterial antigen detection Positive in 50-100%


  14. CSF PREDICTIVE OF BACTERIAL MENINGITIS WITH 99% ACCURACY, IF: • WBC count >2,000 • Neutrophils >1180 • Protein >220 mg/dl • Glucose <34 mg/dl • Glu (CSF/serum): <0.23 Spanos et al. JAMA 1989;262(19):2700-7

  15. What Specific CSF Diagnostic Tests Should Be Used to Determine the Bacterial Etiology of Meningitis? Gram Stain Latex Agglutination (the Practice Guideline Committee does not recommend routine use of this modality): Does not appear to modify the decision to administer antimicrobial therapy False-positive results have been reported Some would recommend it for patients with a negative CSF Gram stain result and may be most useful for the patient who has been pretreated with antimicrobial therapy and whose Gram stain and CSF culture results are negative. Polymerase Chain Reaction (PCR) Broad-based PCR may be useful for excluding the diagnosis of bacterial meningitis, with the potential for influencing decisions to initiate or discontinue antimicrobial therapy. Although PCR techniques appear to be promising for the etiologic diagnosis of bacterial meningitis, further refinements of the available techniques may lead to their use in patients with bacterial meningitis for whom the CSF Gram stain result is negative. CID 2004;39:1267-1284

  16. What Laboratory Testing May Be Helpful in Distinguishing Bacterial from Viral Meningitis? • CSF LACTATE: • Not recommended in suspected community-acquired bacterial meningitis • May be helpful in thepostoperative neurosurgicalpatient, • If CSF lactate concentrations are 4.0 mmol/L, initiation of empirical antimicrobial therapy should be considered pending results of additional studies. • C-REACTIVE PROTEIN: • Normal CRP has ahigh negative predictivevalue in the diagnosis of bacterial meningitis. • Measurement of serum CRP concentration may be helpful in patients with CSF findings consistent with meningitis, but for whom the Gram stain is negative and you’re considering withholding antimicrobial therapy. • PROCALCITONIN: At present, because measurement of serum procalcitonin concentrations is not readily available in clinical laboratories, recommendations on its use cannot be made at this time. • PCR: Enterovirus-PCR (rapid, sensitivity 86-100% specificity 92-100%) CID.2004;39:1267-1284


  18. BACTERIAL MENINGITIS CAN BE “CULTURE-NEGATIVE” • 10-15% of bacterial meningitidis are culture-neg. • Pre-LP use of even oral antibiotics may lower • Gram stain positivity by20% & • Culture positivity by 30% • In children (S.pneumo, H.flu, N. mening.) in 90-100% of pts within 24-36h of “appropriate” antibiotic Rx: • CSF became culture-negative • No sig change in cell count/chemistry. Ped.ID J.1992 11 423-32


  20. INFECTIONS: Viral meningitis (early phase only) Some parameningeal foci/ cerebritis Leakage of brain abscess into ventricle Amebic meningoencephalitis TB meningitis (rarely, & usu. only early) NON-INFECTIOUS: Chemical-meningitis (contrast…) Behcet syndrome Drug –induced ( NSAIDs, Sulfa, INH, IVIG, OKT3…) NEUTROPHILIC PLEOCYTOSIS & LOW CSF GLUCOSEMay Not Always Mean Bacterial Meningitis


  22. PRINCIPLES OF TREATMENTSuspected Bacterial meningitis • Prompt initiation of treatment. • Bactericidal agents, with adequate CSF levels. • Empiric Rx (based on age and predisposing factors) • Specific Rx (based on Gram-stain or antigen). • Include steroids where indicated

  23. .

  24. . a Ceftriaxoneor cefotaxime.b Some experts wouldadd rifampin if dexamethasoneis also given (B-III).cGatifloxaxinor moxifloxacin.d Addition of anaminoglycoside should be considered.

  25. CID.2004;39:1267-1284

  26. Antimicrobial agentTotal daily dose (dosing interval in hours) 9 CID    2004;39:1267-1284

  27. Clinical Infectious Diseases    2004;39:1267-1284

  28. BACTERIAL MENINGITISCASE FATALITY (%) • S. pneumoniae 21 • L. monocytogenes 15 • Group B Strep. 7 • H. influenzae 6 • N. meningitidis 3 NEJM 1997;337:970-6 (based on 248 cases from 4 states, in 1995)

  29. ROLE OF STEROIDS • Decrease subarachnoid space inflammatory response to abx-induced bacterial lysis • Significant reduction in deafness in pediatric H. influenzae & pneumococcal meningitis(JAMA 1997; 278:925). • In adults, reasonable to use steroids: • for pts with evidence of cerebral edema. • for adult with pneumococcal meningitis (Nov 14, 2002 issue of NEJM) Give immediately before or with the 1st dose of antibiotic. Dexamethasone dose: 0.15 mg/kg q6 x 2-4 days

  30. Dexamethasone in Adults with Bacterial Meningitis Jan de Gans,, for the European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators NEJM 2002. 347:1549-1556. (Nov. 14, 2002)

  31. Use of Adjunctive Dexamethasone Therapy in Adults with Bacterial Meningitis • In suspected or proven pneumococcal meningitis cases. • Dexamethasone should only be continued if the CSF Gram stain reveals gram-positive diplococci, or if blood or CSF cultures are positive for S. pneumoniae. • Adjunctive dexamethasone should not be given to adult patients who have already received antimicrobial therapy, because administration of dexamethasone in this circumstance is unlikely to improve patient outcome. • Addition of rifampin to the empirical combination of vancomycin plus a third-generation cephalosporin may be reasonable pending culture results and in vitro susceptibility testing , in patients with suspected pneumococcal meningitis who receive adjunctive dexamethasone. • Some authorities would initiate dexamethasone in all adults because the etiology of meningitis is not always ascertained at initial evaluation, although the data are inadequate to recommend adjunctive dexamethasone to adults with meningitis caused by other bacterial pathogens

  32. Use of Adjunctive Dexamethasone Therapy in Pediatric Patients with Bacterial Meningitis • Infants and Children • Use in H. influenzae typeb meningitis . • For pneumococcal meningitis, controversial. • Neonates • Insufficient data to make a recommendation on the use of adjunctive dexamethasone. CID    2004;39:1267-1284

  33. What Are the Indications for Repeated Lumbar Puncture in Patients with Bacterial Meningitis? • Not indicated routinelyin patients with bacterial meningitiswho have responded appropriately to antimicrobial therapy, • Repeated CSF analysis should be performed in: • Any patientwho has not responded clinically after 48h of appropriate antimicrobialsThis is especially true for the patient with pneumococcal meningitis caused by penicillin-or cephalosporin-resistant strains, especially for those who have also received adjunctive dexamethasone therapy. • Neonate with meningitis due to gram-negative bacillishould have repeated LPs • To document CSF sterilization, because the duration of antimicrobial therapy is determined, in part, by the result. • In patients with CSF shunt infections • The presence of a drainage catheter after shunt removal allows for monitoring of CSF parameters to ensure that the infection is responding to appropriate antimicrobial therapy and drainage). CID    2004;39:1267-1284

  34. PREVENTION OF BACTERIA MENINGITIS • Isolation of index patient • Droplet precautions • For 24 hrs after 1st dose of appropriate abx) • Post-exposure prophylaxis • Vaccination

  35. POST-EXPOSURE PROPHYLAXIS • Candidates: • Household members • Day care center contacts • Direct exposure to pt’s oral secretion ( as in kissing, mouth-to-mouth , intubation/ET tube management) • Index patient (if not treated w 3rd gen cephalosporins) • Regimen: • Meningococcus: Rifampin, ciprofloxacin, or ceftriaxone • Hempohilus influenzae serotype b: Rifampin.

  36. Vaccination • Hib vaccine. • Has had major impact in incidence of pediatric Hib meningitis • Pneumococcal vaccine. • For chronically ill and elderly, & now universal use in children. • PCV-7. Use of PCV-7 for children has been an effective means of preventing disease in older adults (JAMA. Vol. 294 No. 16, October 26, 2005 ) • Meningococcal vaccine • Effective vs serotype A, C, Y, W135 • Major reduction of disease in military recruits • Recommended for travelers to endemic areas. • Offered to college students, specially those residing in dormitory • A new quadrivalent vaccine (Menactra) was recently approved.

  37. Who Should Be Vaccinated with the NEW MENINGOCOCCAL VACCINE(Menactra) • Children aged 11-12 years • Previously unvaccinated adolescents before entering high school or at age 15 (whichever comes first) • All first-year college students living in dormitories • Other high-risk groups, such as those with underlying medical conditions or travelers to areas with high rates of meningococcal disease, such as Africa and India. • Other adolescents who choose to get the vaccine to reduce their risk • "As the vaccine supply increases, CDC hopes, within three years, to recommend routine vaccination [for] all adolescents beginning at 11 years of age," per CDC's news release

  38. FDA and CDC Issue Alert on Menactra Meningococcal Vaccineand Guillain Barre Syndrome • FDA and CDC alerted consumers and health care providers to five reports of Guillain Barre Syndrome (GBS) following administration of Meningococcal Conjugate Vaccine (trade name Menactra). • It is not known yet whether these cases were caused by the vaccine or are coincidental. • Prelicensure studies conducted by Sanofi Pasteur of more than 7000 recipients of Menactra showed no GBS cases. • CDC conducted a rapid study using available health care organization databases and found that no cases of GBS have been reported to date among 110,000 Menactra recipients. • September 30, 2005

  39. CID    2004;39:1267-1284