COMMUNITY%20ACQUIRED%20BACTERIAL%20MENINGITIS%20IN%20ADULTS

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

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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.

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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/strong
  yloides/baylisascaris
• Other infectious syndromes-parameningeal
  focus/IE/postinfectious/postvaccination
• Noninfectious-tumors/medications/SLE/seizures/migr
  aine

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CHANGING EPIDEMIOLOGY

• Since the introduction of H.influenza(1990) and
  Streptococcus pneumonia conjugate vaccine
  (PCV7)(2000) decreased frequency and peak
  incidence has shifted from childrenlt5 to adults
  median age 39. Highest case fatality rates among
  ages gt65
• 90 reduction in incidence of invasive H
  influenza infection.

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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 lt5 and
  9-18,000fewer annually gt5.
• 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

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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

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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
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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

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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

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Meningitis Mortality by Pathogen
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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 lt3 or gt45 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 overdecolorizeso 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

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Pneumococcal meningitis mortality by age
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Mortality and development
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PATHOGENSIS
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TREATMENT GUIDELINES
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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 (gt16)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

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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

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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.

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Dexamethsone in adults with meningitis

• Radomized placebo controlled double blind
  multicenter study with 301 patients from
  Netherlands,Austria,Germany,Belgium,Denmark
• Patientsgt 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(15vs 25)and
  death(7and 15) was significantly lower in the
  dexa group.
• Patients with pneumococcal meningitis had
  significantly less unfavorable outcomes
  (26vs52) and death (14vs 34) with
  dexamethasone
• No benefit with other pathogens
• Greatest benefit with moderate to severe GCS
  score
• All pneumococcal isolates susceptible to Pen

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IDSA recommendations

• Dexamethasone gt15mg/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

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Csf diagnostic tests

• Opening pressure-gt200mm
• Pleocytosis-.1000 ( range lt100,gt10,000)
• Neutraphilic predominance(10 lymphocytic)
• Serum glucose/csf glucose lt.4
• Elevated protein
• Csf culture positive 70-85 without antibiotics

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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

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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

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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

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Treatment
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Antibiotics and release of LTA and TA
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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.

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Duration of treatment
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Synergy of Vancomycin and Ceftriaxome in
experimental meningitis