Transcript bacterial meningitis

COMMUNITY ACQUIRED
BACTERIAL MENINGITIS
IN ADULTS
Julie Hoffman, M.D.
Department of ID
Jacobi Medical Center
Acute Meningitis
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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.
Differential Diagnosis of Acute
Meningitis
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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/helminthsnaegleria/angiotrongylus/strongyloides/baylisascaris
Other infectious syndromes-parameningeal
focus/IE/postinfectious/postvaccination
Noninfectious-tumors/medications/SLE/seizures/migraine
CHANGING EPIDEMIOLOGY
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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.
Impact of PCV7
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CDC study- compared rates of IPD(invasive pneumococcal disease) reported
to 8 US sites participating in Active BacterialCore Surveillance from 19981999 and 2006
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Decreased incidence from 24.4 to 13.5/ 100,000(45%)
IPD due to vaccine serotypes declined 15.5 to 1.3/100000
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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
SEROTYPES CAUSING IPD IN
HIGH HIV PREVALENCE POP
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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
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
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Pediatric Infectious Journal Sept 2009
Serotype 19A in France
 35%
of penumococcus isolated from
two hospitals in France during 2007serotype 19A
 13% of all IPD was due to serotype
19A
 96% resistant to PCN, 95% to
erythromycin
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
Listeria
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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
Pneumococcal meningitis mortality
by age
Mortality and development
PATHOGENSIS
TREATMENT GUIDELINES
NEJM 12/31/01 345:24:1727
Head CT prior to LP
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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
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
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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.
Dexamethsone in adults with meningitis
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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
IDSA recommendations
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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
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
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Csf diagnostic tests
Gram Stain
 Gram stain-accurate id of organism60-90%
 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
Csf diagnostic tests
latex agglutination
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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
Lab testing to distinguish viral from
bacterial etiology
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PCR more sensitive than viral culture-sens 86100%,specificity 92-100%
CRP- high negative predictive value – normal
without meningitis
Treatment
Antibiotics and release of LTA and TA
Rifampin and treatment of
pneumococcal meningitis
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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.
Duration of treatment
Synergy of Vancomycin and
Ceftriaxome in experimental
meningitis