November 4th 2009 PROMPT recognition of Meningitis Rapid Diagnostic testing to identify the etiologic pathogen and adjust therapy Rapid Initiation of appropriate Empiric Antimicrobial.
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Transcript November 4th 2009 PROMPT recognition of Meningitis Rapid Diagnostic testing to identify the etiologic pathogen and adjust therapy Rapid Initiation of appropriate Empiric Antimicrobial.
November 4th 2009
PROMPT recognition of Meningitis
Rapid Diagnostic testing to identify the
etiologic pathogen and adjust therapy
Rapid Initiation of appropriate Empiric
Antimicrobial therapy
Targeted Antimicrobial therapy
Do’s and Don’ts for the Boards
1805-1900’s: ~100% fatal
1913: Flexner: intrathecal meningococcal
antiserum. Prevented some deaths
1930’s: Antibiotics. Improved survival
Current data:
Adults: 25% mortality, 21-28% neurologic
sequelae
Bacterial meningitis remains a
medical emergency!
RECOGNIZE
Clinical picture is often “unimpressive”
when the patient is first seen
URI interrupted
by one of the
“meningeal
symptoms”:
vomiting,
headache,
lethargy,
confusion, stiff
neck
aLTERED mENTAL sTATUS
FEVER
HEADACHE
1. AGE
2.SEASON
3.Geography
4.Predisposing factors
(immunocompromised state; basilar skull
fracture with CSF leak; head trauma; post
neurosurgical procedures ~wound and FB)
5.Onset and duration of illness (acute;
subacute and chronic) ~community aquired
or nosocomial
6.Travel,occupational and recreational
exposures( insect and animal contact)
7. Vaccination history and current meds (ABX)
8.Parameningeal foci or septic emboli from IE
9. Imaging before Lumbar puncture
10. Gram stain and Interpretation of the CSF
formula
14-year-old male with no significant PMH is
admitted to the hospital with acute onset of
high fever, chills, sore throat, stiff neck, and
lethargy
T 1040F, P 120, RR 32, BP 70/30 mmHg
On examination, he was oriented only to person,
and had evidence of nuchal rigidity
WBC 25,000/mm3 with 20% bands
CSF WBC 1,500/mm3 (98% neutrophils), glucose
20 mg/dL, and protein 200 mg/dL
A
B
C
D
E
Haemophilus influenzae type b
Neisseria meningitidis
Streptococcus pneumoniae
Enterovirus 71
Cryptococcus neoformans
LOOK @ AGE/ARMY
RECRUITS/COLLEGE
STUDENTS/
Rash
Affects mostly children and young adults;
mortality 3-13% (SPORADIC 98% cases B)
Epidemics usually caused by serogroups A and C
Group Y strains associated with pneumonia
Serogroup C disease increasing in the US
Nasopharyngeal acquisition of infection
Predisposition in those with congenital
deficiencies in terminal complement
components (C5-C9) and properdin
deficiencies
PEN G and AMPICILLIN are DRUGS OF
CHOICE
Empiric therapy with Third Generation
Cephalosporins recommended
Nasopharyngeal carrier state 10 to 15%
Infection control DROPLET precautions
~surgical mask
21-year-old male without significant PMH was found
difficult to arouse by his roommate in his college
dormitory. Patient taken via fire rescue to ER
On exam, he was lethargic, febrile to 1030F,
tachycardic, tachypnec, and hypotensve. His neck
was stiff and he had a petechial rash on the lower
extremities
CSF revealed a neutrophilic pleocytosis, low glucose,
and elevated protein. Gram’s stain showed gramnegative diplococci
The patient received IV penicillin G and made a full
recovery. Blood and CSF grew Neisseria meningitidis
For which of the following persons is
antimicrobial chemoprophylaxis
recommended?
The Dean of the college
The ambulance driver
The emergency room physician
The triage nurse
The patient
Household members
Day care center contacts
Persons directly exposed to patient’s oral
secretions - kissing, mouth-to-mouth
resuscitation
- endotracheal intubation or endotracheal tube
management
Index patient if not treated with a third
generation cephalosporin
Chemoprophylactic regimens
- rifampin
- ceftriaxone
- ciprofloxacin - azithromycin
Immunocompromised
patients
H/O CNS disease
New onset SEIZURE
Focal neurological
signs
Altered consciousness
Papilledema
Delay in performing LP
Do Blood Cx STAT
Dexamethasone and
empiric antimicrobials
CT scan
LP if CT negative
Normal
0-5
0
5
60-80
66%
Bacterial
>1000
Viral
<1000
TB
25-500
Predominate
Early
+/- increased
Late
Predominate
Increased
Decreased
Normal
Decreased
<40%
Normal
< 30%
Protein
5-40
Increased
+/- Increased
Increased
Culture
Negative
Positive
Negative
+TB
Cells
Polymorphs
Lymphocytes
Glucose
CSF
plasma:
Glucose
ratio
Gram stain
Positive in 60-90%
Culture
Positive in 70-85%**
Blood Culture
CSF
Positive in 50%
** Beware of partially treated meningitis with abx for
2-3 days this may give you negative Cx although CSF
remains abnormal; Shift from PMN to polys and
lymphs or lymphocytic predominance
Do NOT assume this is NOT a bacterial infection
Gram negative:
Diplococci: Meningococcus
Bacilli: E. coli
Coccobacilli: H influenzae
(small, pleomorphic)
Gram Positive:
Diplococci: Pneumococcus
Chains: Strep Group B
Clusters: Staph
Rods & cocobacilli: Listeria
56-year-old female with a 2-day history of
fever, chills, headache, and confusion. Saw
her physician 5 days earlier with complaints
of earache; received ciprofloxacin
T 1030F, P 140, RR 32, BP 90/60 mmHg
Obtunded, stiff neck, purpuric rash on lower
extremities
CSF showed opening pressure of 280 mm
H2O, WBC 2,500/mm3 (99% neutrophils),
glucose 15 mg/dL, protein 400 mg/dL
Which of the following regimens should be
initiated?
A Dexamethasone + Penicillin G
B Dexamethasone + Ceftriaxone
C Dexamethasone + Vancomycin + Ampicillin
D Dexamethasone + Vancomycin +
Ceftriaxone
E Vancomycin + Ceftriaxone
Most common etiologic agent in US
Mortality of 19-26%
Associated with other suppurative foci of
infection ~ Pneumonia (25%)
Otitis media or mastoiditis (3 0%)
Sinusitis (10-15%)
Endocarditis (<5%)
Head trauma with CSF leak (10%)
PCN MIC µg/ml
Antimicrobial therapy
<0.1
PCN G or Ampicillin
0.1-1.0
Third generation Cephalosporin
>1.0
Vancomycin + third generation
cephalosporin*
>2.0
Vancomycin + third generation
cephalosporin **
•*Cefotaxime or ceftriaxone
**Consider addition of Rifampin if
Ceftriaxone MIC > 2
!! REMEMBER SUSCEPTIBILITIES ARE
NOT ROUTINELY DONE
Microorganism
S. pneumoniae
Antimicrobial Therapy
Vancomycin + a third generation
cephalosporina,b
N. meningitidis
Penicillin G, ampicillin, or a
third generation cephalosporina
H. influenzae type b
Third generation cephalosporina
L. monocytogenes
Ampicillin or penicillin G*
S. agalactiae
Ampicillin or penicillin G*
E. coli
Third generation cephalosporina
acefotaxime
baddition
*addition
or ceftriaxone
of rifampin may be considered, especially if dexamethasone given
of an aminoglycoside may be considered
Attenuates subarachnoid space inflammatory response resulting from
antimicrobial-induced lysis
Recommended for infants and children with Haemophilus influenzae
type b meningitis and considered for pneumococcal meningitis in
childhood, if commenced with or before parenteral antimicrobial
therapy
Clinical trials (predominantly in infants and children) have demonstrated
reduction in neurologic and/or audiologic sequelae
Recommended in adults with pneumococcal meningitis
Administer at 0.15 mg/kg every 6 hours for 2-4 days concomitant with or
just before first antimicrobial dose
Tuberculous Meningitis
– Corticosteroids (extreme neurologic
compromise, elevated ICP, impending
herniation, impending or established spinal
block;
CT/MR evidence of hydrocephalus or basilar
meningitis)
Cryptococcal Meningitis
– Reduction in intracranial pressure (frequent
high- volume lumbar punctures, VP shunts)
60-year-old male with acute myelogenous leukemia
presented with fever, headache, ataxia, and altered
mental status. Recently traveled to an outdoor family
picnic in rural Virginia. He is allergic to penicillin
(anaphylaxis)
T 102oF, P 120, RR 24, BP 100/60
On examination, he was obtunded and had nuchal
rigidity. Funduscopic exam revealed no papilledema.
Babinski responses were positive bilaterally
WBC was 25,000/mm3 (30% bands)
LP revealed a WBC 1500/mm3 (50 neutrophils, 50%
lymphocytes), glucose 30 mg/dL, and protein 200
mg/dL
Which of the following antimicrobial
regimens should be initiated?
A Vancomycin administered intravenously
and intrathecally
B Vancomycin + rifampin
C Chloramphenicol
D Trimethoprim-sulfamethoxazole
E Erythromycin
Mortality 15-29%
Rare cause of bacterial meningitis in US (8%)
Outbreaks associated with consumption of
contaminated coleslaw, raw vegetables, milk,
cheese, processed meats
Common in neonates (~20% of cases)
Disease in adults associated with:
Elderly Alcoholism
Malignancy
Immune suppression
Diabetes mellitus
Hepatic and renal disease
Iron overload Collagen-vascular disorders
CASE #2
46-year-old male executive from Phoenix,Arizona
presents to the ER with recent history of going on a
cruise to Jamaica. One week after returning, he
developed headaches, stiff neck, and vomiting.
He had no significant PMH and was sexually active
with multiple partners.
Physical exam revealed low-grade fever and
meningismus, but was otherwise negative.
CSF examination revealed a WBC count of 300/mm3
with 60% eosinophils, glucose of 45 mg/dL and
protein 150 mg/dL.
Gram stain was negative.
Which of the following is the most likely
cause of this patient’s illness?
Treponema pallidum
Mycobacterium tuberculosis
Coccidioides immitis
Angiostrongylus cantonensis
Lymphoma
Most common cause of eosinophilic meningitis
Reported from many countries of the world (Thailand,
Malaysia, Vietnam, Indonesia, Papua New Guinea,
Taiwan, Pacific Islands); recent outbreak in Jamaica
Rat infection rate in urban Bangkok ~40%
May spread as rats move freely from port to port on ships
Symptoms begin 6-30 days after ingestion of raw
mollusks or other sources of the parasite.
Clinical findings are headache (90%), stiff neck (56%),
paresthesias (54%), and vomiting (56%)
CSF reveals a moderate pleocytosis with 16-72%
eosinophils; larvae are occasionally found in CSF
Usually self limited course and recover
completely
Analgesics
Corticosteroids
Frequent but careful LPs if increased
intracranial pressure
May present acutely, although usually subacute to
chronic
Patients generally complain of headache, low-grade
fever, weight loss, and mental status changes;
signs of meningeal irritation are usually absent
Serum complement-fixing antibody titers >1:32 to
1:64 suggest disseminated disease
CSF examination may occasionally reveal a prominent
eosinophilia; CSF protein is almost always elevated
Only 25-50% of patients have positive CSF cultures
CSF complement-fixing antibodies present in at least
70% of cases; titers parallel course of meningeal
disease
60 year old male with ESRD immigrated from
Brazil to US and underwent a cadaveric renal
transplant. Prior to transplant, he had
recurrent epigastric pain.
WBC 6,500 with 15% eosinophils
After transplant received Prednisone and
Azathioprine
Presented 1 month later with T 39ºC,
headache, meningismus and altered mental
status
Lumbar puncture showed
WBC 2500/mm³
(98% neutrophils)
Glucose 20 mg/dl
Protein 450mg/dl
Placed on Empiric Vancomycin, Ampicillin
and Ceftriaxone
Blood cultures and CSF Cx grew E.coli
Which of the following diagnostic test would
most likely establish the pathogenesis of
E.coli meningitis in this patient?
A. CT scan of the head and sinuses
B. Bronchoscopy with transbronchial lung
biopsy
C. Serial stool examinations
D. Meningeal Biopsy
E. Metrizimide cisternography
Klebsiella species, Escherichia coli, Serratia
marcescens, Pseudomonas aeruginosa,
Salmonella species
Isolated from CSF of patients following head
trauma or neurosurgical procedures
Cause meningitis in neonates, the elderly,
immunocompromised patients, and in patients
with gram- negative septicemia
Associated with disseminated strongyloidiasis
in the hyperinfection syndrome
An 80-year-old male is brought to the hospital by his
family because of personality changes and olfactory
hallucinations
On exam, T 1010F, P 90, RR 16, BP 120/90 mmHg
He is confused and oriented only to person. There is
no meningimus or evidence of focal neurologic
deficits
CT of head without contrast is negative; CSF reveals a
WBC of 90/mm3 (95% lymphocytes), glucose of 80
mg/dL (serum 100 mg/dl), and protein of 70 mg/dL
Which of the following is the best test for
establishing the diagnosis in this patient?
A Electroencephalogram
B MRI of head with gadolinium
C Brain biopsy
D CSF polymerase chain reaction
E CSF antibody studies
50-year-old man evaluated
for obtundation and fever
Brain MRI with gadolinium
reveals swelling and
enhancement of the left
temporal lobe; CSF
analysis reveals a WBC of
10/mm3, normal glucose
and elevated protein
Intravenous acyclovir is
initiated
CSF PCR for HSV 1 and
HSV 2 are negative
Which of the following is the appropriate
management for this patient?
A. Discontinue acyclovir
B. Perform a brain biopsy
C. Begin ganciclovir + foscarnet
D. Send CSF for HHV6 PCR
E. Perform HSV PCR on a new CSF specimen
Neuroimaging
– MRI is procedure of choice (AFTER LP)
– Edema and hemorrhage in temporal lobes
– Bilateral temporal lobes (pathognomonic)
CSF Analysis
– Lymphocytes, increased protein, normal
glucose – Polymerase chain reaction
EEG
– Periodic lateralizing epileptiform discharges
Published reports have found that false
negatives can occur due to testing
Too early or too late,
improper sample transport,
or low volumes of CSF tested.
HSVE is frequently fatal untreated. Therefore, if
MRI shows compatible temporal lobe findings
and no alternative diagnosis is established,
continued treatment with acyclovir should be
strongly considered.
A second spinal tap with repeat CSF PCR or a
brain biopsy may be indicated.
75 year old woman from Colorado presents
with acute onset of altered mental status and
fever
Neurological examination reveals bilateral
tremors of theextremities and cogwheel
rigidity
Brain MRI reveals T1 hypodense lesions in the
thalamus and basal ganglia that are
hyperintense on T2 images
CSF Analysis reveals a WBC of 300/mm³
glucose of 70 and protein of 105.
Which of the following tests is most likely to
confirm the diagnosis in this patient?
A. Serum Ig M antibody
B. Serum Ig G antibody
C. CSF IgM antibody
D. CSF PCR
E. Brain Biopsy
First US cases reported in 1999 in New York
City
Birds are main reservoirs
Transmission
-mosquito vector
-transfusion
-transplantation
-Breast feeding
Clinical
features of
WNV
Age >50 years~ increased incidence
1/150 develop neuroinvasive disease
Tremors and Myoclonus
Parkinsonism
Poliomyelitis like flaccid paralysis
Serum IgM and IgG capture ELISA
(cross reactivity with other
flaviviruses)
CSF IgM antibodies (diagnostic of
neuroinvasive disease)
CSF PCR (positive in <60%)
Etiologies of Viral
encephalitis
Echo virus
Coxsakie and
Enteroviruses
Herpes Simplex
West Nile virus
Un identified etiology
32- 75%
Herpes Encephalitis
is
“NOT SEASONAL”
sporadic
**Clues !!!
epidemiological
factors
THERAPY FOR ENCEPHALITIS
Etiology
Therapy
HSV
Acyclovir
VZV
Acyclovir
CMV Ganciclovir + foscarnet
HHV-6 Ganciclovir or
foscarnet
HIV
HAART
JC virus HAART
56 year old man s/p Kidney transplant in 2006
s/p Left mastectomy for a painful mass on
Sept 1st 2009 discharged POD # 3
re-admitted a week later with urinary
retention and rectal bleeding.
Unclear cause of urinary retention relieved
after foley catheter insertion
Rectal bleeding attributed to constipation
and a bowel regimen ordered by general
surgery
Day 4 of admission patient began to have some
hallucinations and beginning confusion.
Agitation increased gradually over the next few
days.
CT Brain No acute abnormality MRI ( X AICD )
Day 7 after admission; after a bowel movement
patient is turned back to supine position turns
gray codes and is intubated ( ?Aspiration)
Day 14 ID is consulted for a persistent fever on
Vancomycin and Cefepime with a RLL
Pneumonia
Patient was on Haldol round the clock for
severe agitation attributed to ICU
delirium..initially sleep deprivation
WHAT ARE WE MISSING?
Fever, altered mental status
in an Immuno-compromised host ???????
CONFOUNDERS pneumonia with
Achromobacter Xylosoxidans I to cefepime
Noninvasive testing was ordered and so was
and LP
Serum Cryptococcal Antigen was 1:1024!!!!
CSF CrAG was 1:2084
Protein was 594
Glucose was 37
CSF wbc
Neutrophils
Lymphocytes
Patient was initiated on High dose
Fluconazole and 5 Flucytosine without
reversal of neurological status.
He underwent trach and peg and died 2
weeks after initiation of therapy.
CSF parameter
NON –AIDS(%)
AIDS(%)
Blood cultures
-
30- 63%
Serum CrAG
66%
99%
Opening pressure>200 mm
H2O
72%
62- 66%
CSF Glucose < 40mg/dl
73%
33%
CSF protein>45mg/dl
89%
58%
CSF Leukocytes > 20/mm³
70%
13 -31%
CSF Culture
96%
95%
CSF CrAG
86%
91-100%
Septic Emboli with Infective Endocarditis
Brain Abscess
Secondary Syphilis
Parameningeal focus
Rocky mountain Spotted fever ~ Doxycycline
Aspetic Meningitis like picture
Leptospirosis~ water rodent exposure Hepatitis/ meningitis
LYME disease
Lymphocytic choriomeningitis ~grip like illness Influenza like
2000-3000 lymphocytes / winter peak
Mumps~ peaks in winter with orchitis and parotitis
Brucellosis
Midline tumors craniopharyngiomas
MEDS NSAIDs ( afebrile)
Tunkel AR, Hartman BJ, Kaplan SL, et al.
Practice guidelines for the management of
bacterial meningitis. Clin Infect Dis
2004;39:11267-84.
Spanos A, Harrell FE Jr, Durack DT.
Differential diagnosis of acute meningitis:
an analysis of the predictive value of initial
observations. JAMA 1989;262:2700-7.