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COMMUNITY ACQUIRED BACTERIAL MENINGITIS IN ADULTS Julie Hoffman, M.D. Department of ID

COMMUNITY ACQUIRED BACTERIAL MENINGITIS IN ADULTS Julie Hoffman, M.D. Department of ID Jacobi Medical Center. Acute Meningitis. Meningitis-inflammation of the meninges, identified by abnormal WBCs in CSF

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COMMUNITY ACQUIRED BACTERIAL MENINGITIS IN ADULTS Julie Hoffman, M.D. Department of ID

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  1. COMMUNITY ACQUIRED BACTERIAL MENINGITIS IN ADULTS Julie Hoffman, M.D. Department of ID Jacobi Medical Center

  2. Acute Meningitis • Meningitis-inflammation of the meninges, identified by abnormal WBCs in CSF • Clinically defined as syndrome characterized the onset of meningeal symptoms over the course of hours to up to several days .HA is a prominent early symptom followed by confusion and coma. • Blurs into chronic meningitis( onset weeks to months) and encephalitis which is distinguished by decreased mentation with minimal meningeal signs.

  3. Differential Diagnosis of Acute Meningitis • Infectious • Virus-nonpolio enterovirus,arbovirus,herpesvirus, LCM virus, HIV, adenovirus, influenza • Richettsia • Bacteria-H influ, N mening, S pneum, Listeria, E coli, Strep agal, propionobacteria,staph, enterococcus, Klebs, Salmonella, Norcardia, Strep pyogenes, MTB, • Spirochetes • Protozoa/helminths-naegleria/angiotrongylus/strongyloides/baylisascaris • Other infectious syndromes-parameningeal focus/IE/postinfectious/postvaccination • Noninfectious-tumors/medications/SLE/seizures/migraine

  4. CHANGING EPIDEMIOLOGY • Since the introduction of H.influenza(1990) and Streptococcus pneumonia conjugate vaccine (PCV7)(2000) decreased frequency and peak incidence has shifted from children<5 to adults median age 39. Highest case fatality rates among ages >65 • 90% reduction in incidence of invasive H influenza infection.

  5. Impact of PCV7 • CDC study- compared rates of IPD(invasive pneumococcal disease) reported to 8 US sites participating in Active BacterialCore Surveillance from 1998-1999 and 2006 • Decreased incidence from 24.4 to 13.5/ 100,000(45%) • IPD due to vaccine serotypes declined 15.5 to 1.3/100000 • Nonvaccine serotypes increased 6.1to 7.7/100,000.Serotype 19A form .8-2.7 • 11-15,000 cases of IPD annually in <5 and 9-18,000fewer annually >5. • 10,000 fewer deaths, .170,000 cases of IPD prevented with vaccine since introduction • Increase in antibiotic nonsusceptible strains in 2006 • 75% of strains serotype 19A icaac/idsa 2008 abstact g-761

  6. SEROTYPES CAUSING IPD IN HIGH HIV PREVALENCE POP • IPD SURVEILLANCE IN 3 NEWARK HOSPITALS(HIV PREV 2%)-BLOOD/CSF CULTURES 12/07-4/30/08 • 41/48 ANALYZED FOR SEROTYPE • 37 ADULTS(MEDIAN age 52)AA76%,HISP24%,HIV32% • 31(94%) NONVACCINE SEROTYPE(NVT)-19A (39%) • 9(22%)PCN RESISTANT-19A 7/9 ICAAC/IDSA 2008 ABSTRACT G-2075

  7. Emergence of serotype 19a in children • Texas Childrens Hospital • 1/07-7/08 248 sinus cultures via nasal endoscopy in recurrent or chronic sinusitis • 24 pneumococcal isolates- 21 nonvaccine serotypes • 12 serotype 19A-4 mdr( res pcn/cef/erythro/clinda/bactrim) 7 resistant to PCN Pediatric Infectious Journal Sept 2009

  8. Serotype 19A in France • 35% of penumococcus isolated from two hospitals in France during 2007- serotype 19A • 13% of all IPD was due to serotype 19A • 96% resistant to PCN, 95% to erythromycin

  9. Specific Organisms • Multicenter study in US in 1995 (after H influ vaccine) frequency of pathogen varied with age. Reduction of 55% compared with 1985 • Adults less than 60, S pneu. -60%, N.mening- 20%, H influenza -10%,Listeria-6%, GBS -4% • Over 60, S pneum-70%, Listeria 20%, GBS/N.meningitis/H influenz-3-4%

  10. Meningitis Mortality by Pathogen

  11. Listeria • Leading predisposing factors: hematologic malignancy, solid tumors, kidney transplant, also hemochromatosis; in recent series 31% had no underlying disease. • Intracellular pathogen; macrophage dysfunction predisposes. • Occurs more often in age <3 or >45 years • Pts. with Listeria have fewer meningeal signs, less likely to have high CSF white count and protein than other pathogens. • Gram stain of CSF negative in 2/3rds of patients Can overdecolorize—so difficult to identify! • CSF may be normal early in infection; with suggestive signs/symptoms repeat LP in 12-24 hours. • Can have localized brain abscess and meningoencephalitis • Outbreaks are usually foodborne: cheese, coleslaw, meat products; 5% of people are asymptomatic carriers

  12. Pneumococcal meningitis mortality by age

  13. Mortality and development

  14. PATHOGENSIS

  15. TREATMENT GUIDELINES

  16. NEJM 12/31/01 345:24:1727

  17. Head CT prior to LP • Risk of herniation after LP varies among studies • Study from 1959-129 patients with increased ICP- 1.2% with papilledema/12% without herniated after LP • LP results in small transient decreases in CSF pressure throught subarachnoid space as a result of removal of fluid and continued leakage. • Herniation may occur in space occupying inflammatory lesions(empyema/abscess/toxo),tumor, hemorrage esp rapidly expanding. Also with meningitis with inc ICP with cerebral edema, thrombosis of sagital sinus, occlusion of villi. Herniation may also occur without LP • 1995-1999, 301 adults (>16)with clinically suspected meningitis presenting to Yale ED prospectively evaluated to identify clinical and lab features that would predict CT abnormalities. • 235(78%) had CT before LP

  18. CT before LP • 96/235 had none of these risks • 3/96 had abnormal CT findings but no herniation. • 4/235 had mass effect and no LP performed • LP delayed average of two hours in group undergoing CT • Even with normal CT, clinical signs suggestive of high ICP should caution against LP

  19. Neurologic Outcomes • Unfavorable neurological outcomes not completely the result of inadequate treatment with antibiotics. CSF cultures are sterile within 24-48 hours after starting antibiotics. In animal studies, pneumococcal and gram negative(meningococcus/H flu) induce meningitis and death. Steroids reduce both csf inflammation and neurologic sequelae in some infections.

  20. Dexamethsone in adults with meningitis • Radomized placebo controlled double blind multicenter study with 301 patients from Netherlands,Austria,Germany,Belgium,Denmark • Patients> 17 with suspected meningitis randomized to receive dexa 10 mg q 6 x4 days or placebo given 15-20 minutes before antibiotics • 8 weeks after enrollment, percentage of patients with unfavorable outcome(15%vs 25%)and death(7%and 15%) was significantly lower in the dexa group. • Patients with pneumococcal meningitis had significantly less unfavorable outcomes (26%vs52%) and death (14%vs 34%) with dexamethasone • No benefit with other pathogens • Greatest benefit with moderate to severe GCS score • All pneumococcal isolates susceptible to Pen

  21. IDSA recommendations • Dexamethasone >15mg/kg q6h for 2-4 days with the first dose 10-20 minutes before or with the first dose of anibiotics • Continue if csf gram stain with gram pos diplococci or cultures positive for pneumococcus • Do not use in patients who have already received antibiotics • Unknown benefit with resistant pneumococcus. • Dexa decreases vanco penetration

  22. Csf diagnostic tests • Opening pressure->200mm • Pleocytosis-.1000 ( range <100,>10,000) • Neutraphilic predominance(10% lymphocytic) • Serum glucose/csf glucose <.4 • Elevated protein • Csf culture positive 70-85% without antibiotics

  23. Csf diagnostic testsGram Stain • Gram stain-accurate id of organism-60-90% • Dependent on concentration of bacteria and organism-S pneum-90% cases, h.infl-86%, n mening- 75%,gram neg-50%,listeria-30% • 20% lower with prior antibiotics • False positive-contaminated with skin fragment

  24. Csf diagnostic testslatex agglutination • Most useful in patients treated with antibiotics and whose gram stain and culture are negative • 901 csf bacterial antigen tests performed over 37 months-no modification of therapy in 22/26 positives • 344 csf specimens-10 true pos( pos culture)-3 false neg/2 false pos. no change in management

  25. Lab testing to distinguish viral from bacterial etiology • PCR more sensitive than viral culture-sens 86-100%,specificity 92-100% • CRP- high negative predictive value – normal without meningitis

  26. Treatment

  27. Antibiotics and release of LTA and TA

  28. Rifampin and treatment of pneumococcal meningitis • AAC 2003-Gerber et al • Rabbits with pneumococcal experimental meningitis treated with rifampin followed by ceftriaxone. • Significant decrease in LTA and neuronal apoptosis on autopsy.

  29. Duration of treatment

  30. Synergy of Vancomycin and Ceftriaxome in experimental meningitis

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