Transcript Fast review of CNS Infections

Fast review of CNS
Infections
Husain Alawadhi
Consultant intensivist, pulmonologist and
Infectious disease.
Guideline in Progress :summer 2008
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"The Management of Encephalitis: Clinical
Practice Guidelines by the Infectious
Diseases Society of America“
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Coming soon
ACUTE CNS INFECTIONS
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Bacterial meningitis
Meningoencephalitis
Brain abscess
Subdural empyema
Epidural abscess
Septic venous sinus
thrombophlebitis
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Etiology
Pathogenesis
Microbiology
Diagnosis
Treatment
Complication
Prevention
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ETILOGY
Mucrobiology by age
Figure 24-8
Bacterial Meningitis
Important Changes in Epidemiology
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Marked decline in the occurrence of Hib
↑’ing incidence of S. pneumo (50+% of cases
in US)
Shift from peds disease to adult disease
↑’ing incidence of ATB-resistant organisms,
esp. S. pneumo
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PCN resistance ~ 35% (15-20% high level)
Ceph resistance 15-20% (5-10% high level)
Risk Factors for Drug-Resistant
S. pneumoniae (DRSP)
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Extremes of age
Recent ATB Rx
Significant comorbid disease
HIV infection or other immunodeficiency
Day care or day care parent/sib
Recent hospitalization
Congregate settings (Institutions, military)
VIRAL MENINGITIS/ENCEPHALITIS
Herpesviruses
Herpes simplex
Varicella-zoster
Epstein Barr
Cytomegalovirus
Myxo/paramyxoviruses
Influenza/parainfluenzae
Mumps
Measles
Miscellaneous
Adenoviruses
LCM
Rabies
HIV
Enteroviruses
Polioviruses
Coxsackieviruses
Echoviruses
Togaviruses
Eastern equine
Western equine
Venezuelan equine
St. Louis
Powasson
California
West Nile
Rare parsitic meningitis
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The most important are in the genera
Naegleria and Acanthamoeba. Naegleria
fowleri, the main protozoan causing primary
amebic meningoencephalitis in humans, has
been recovered from lakes, puddles, pools,
ponds, rivers, sewage waters.
DIAGNOSIS
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CSF: Some Catches
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Protein least specific
TB: early neutrophilic
predominance
Encephalitis, RMSF, tick-borne
illnesses: inc CSF WBC
Listeria: misread as
“contamination”/diphtheroids
Listeria: bacterial meningitis that
can have significant encephalitis and
abscess, and CSF with lymphocytes!
RBCs that do not clear: SAH or
HSV
CSF: More Pearls
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Correction factors for traumatic tap
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“trauma” and RBCs increase
protein and with an increase in
RBCs come an increase in WBCs
True CSF protein = subtract 1
mg/dL protein for every 1000
RBC/mm3
True WBC in CSF: actual WBC in
CSF – (WBC in blood x RBC in
CSF)/ RBC in blood
Contraindications to LP
Absolute:
Relative:
Skin infection over site
Papilledema, focal neuro signs, ↓MS
Increased ICP without papilledema
Suspicion of mass lesion
Spinal cord tumor
Spinal epidural abscess
Bleeding diathesis or ↓ plts
CSF pressure
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Normal opening pressure
in adults is 90~180mmH2O,
10~100mmH2O in children.
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Elevated in :
Congestive heart failure
Meningitis
Superior vena cava syndrome
Cerebral edema
Mass lesion
Decreased In
Spinal-subarachnoid block
Dehydration
Circulatory collapse
CSF leakage
Diagnostic Accuracy of Signs of Meningeal
Irritation in Pts with Suspected Meningitis
Sign
Nuchal
rigidity
Kernig’s
Brudzinski’s
Sens Spec PPV NPV +LR -LR
30%
5%
5%
68%
26%
73%
95%
95%
27%
27%
72% 0.97
72% 0.97
Thomas KE et al, CID 2002, 35:46-52
0.94
1.02
1.0
1.0
CSF Findings
WBC
(TNC)
Normal
Bacterial
Viral
Fungal
TB
other
0-5
10010,000
5-3000
5-500
5-500
paraneo
>50%
PMN
>50%
lymphs
>50%
lymphs
>50%
lymphs
Monoclon
al, atypia
Cell type
Protein
50-80
mg/dL
>200
Nl/slight
increase
Nl/slight
increase
Increase
increased
Glucose
70-80
mg/dL
>60%
serum
<40,
<60% of
serum
glucose
Normal
normal
<40 or nl
decrease
60% +
Neg
50% india
ink +
crypto
AFB +
25-35%
Inc
Nl
Inc
Nl/inc
Gm stain
Pressure
75-200
mm Hg
CSF SMEARS & STAINS
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GmS + in 60-90% of pts with
untreated bacterial meningitis
With prior ATB Rx, positivity of GmS
decreases to 40-60%
REMEMBER: + GmS = Heavy
organism burden & worse prognosis
CCT Before LP in Patients with
Suspected Meningitis
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301 pts with suspected meningitis; 235
(78%) had CCT prior to LP
CCT abnormal in 56/235 (24%); 11 pts (5%)
had evidence of mass effect
Features associated with abnl CCT were age
>60, immunocompromise, H/O CNS dz,
H/O seizure w/in 7d, & selected neuro abnls
Hasbun, NEJM 2001;345:1727
Guidelines : Do CT before LP in the
following cases
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Any immunocompromised patient.
New Convulsion
Papillodema
Any previous CNS pathology
Abnormal Lovel of consciousness
Focal neurological deficits
Age > 65
BACTERIAL VS VIRAL MENINGITIS
Predictors of bacterial etiology:
 CSF glucose < 40
 CSF protein > 60
 CSF neutrophil count > 80%
 CSF WBC count > 100
 CSF: Serum glucose ratio < 0.23
[Presence of any ONE of the above findings
predicts bacterial etiology with > 75% certainty]
BACTERIAL VS VIRAL MENINGITIS
Predictors of bacterial etiology:
 CSF glucose < 34
 CSF: Serum glucose ratio < 0.23
 CSF protein > 220
 CSF WBC count > 2000
 CSF neutrophil count > 1180
[Presence of any ONE of the above findings
predicts bacterial etiology with > 99%
certainty]
Strep Pneumoniae Meningitis
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Now most common cause (H flu rare)
30-50% cases of bacterial meningitis in elderly
Otitis 30%, sinusitis 8%, pneumonia 18%
Elderly more often have pneumonia (bad)
Bad markers: older age, low platelets, dec CSF glucose, no
otogenic focus
Vaccination: recommended in all over age 65
 Efficacy in elderly/immunocompromised NOT clear
 Decrease bacteremia/meningitis
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Listeria
Food-borne outbreaks
Herd animals
Common, likely cause of mild GI illnesses
Invasive disease with bacteremia
Increased risk with depressed cellular immunity: pregnant women, elderly,
AIDS, lymphoma, steroid use, transplant patients Small, anaerobic gm +
baccillus
Look like diphtheroids, contaminants Diphtheroids in CSF: listeria unless
proven otherwise
Cerebritis, brain abscess
Confusion, altered LOC, seizure, movement
Mortality 22% in older patients with CNS dz
20% of all cases of bacterial meningitis in patients over age 60
Brain abscess: 10% CNS infections
 Concomitant meningitis in 25-40% (rare with other causes of brain abscess
ER management of meningitis
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TREATMENT
Empirical threapy
Specific therapy
Review: Van Der Beek et al,
Lancet March 2004
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Systematic review
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Age> 16
At least 1 fatality
Jadad Scale
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Outcomes
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Randomization 0-2
Double Blinding 01
Withdrawls/Dropouts 0-1
Organism
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kkfsfa
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Mortality
Neurological deficits
S.Pneumo
N. Meningitidis
Other
Adverse Events
Conclusion: Steroid therapy in all pt’s with suspected bacterial meningitis
Benefit in studies reviewed are seen when dexamethasone is started with or soon
after antibiotics
NEJM, 2006;354, 44-53
BACTERIAL MENINGITIS
Duration of ATB Rx
Pathogen
Duration of Rx (d)
H. influenzae
7
N. meningitidis
7
S. pneumoniae
10-14
L. monocytogenes
14-21
Group B strep
14-21
GNRs
21
NEJM 1997;336:708
THE PATIENT WITH SUSPECTED CNS
INFECTION
Role of Repetitive LP’s
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Rarely indicated in proven bacterial meningitis unless
clinical response not optimal or as expected, fever
recurs, or infection is due to ATB resistant
pathogen
Essential in pts with “aseptic meningitis” syndromes to
monitor course &/or response to empiric therapies
Essential in pts with subacute/chronic meningitis of
proven etiology to assess response to Rx
Not routinely indicated at end-of-therapy for bacterial
meningitis
後記
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The available evidence supports the use of
adjunctive dexamethasone in infants and children
with H. influenzae type b meningitis. ( 0.15 mg/kg
every 6 h for 2-4 days)
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Dexamethasone in adults with the adjunctive
dexamethasone be administered to all adult
patients with suspected or proven pneumococcal
meningitis. ( 0.15 mg/kg every 6 h for 2-4 days)
FDA warning 9/11/2007
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Rocephin (ceftriaxone
sodium) for Injection
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Potential risk associated
with concomitant use of
Rocephin with calcium or
calcium-containing
solutions or products
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Cases of fatal reactions with
calcium-ceftriaxone
precipitates in the lungs and
kidneys in both term and
premature neonates were
reported.
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COMPLICATIONS
Extradural Abscess
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Extradural abscess,
associated with osteomyelitis,
complication of sinusitis or a surgical
procedure.
When the process occurs in the spinal epidural
space, it may cause spinal cord compression
and constitute a neurosurgical emergency.
subdural empyema.
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fungal infection of the skull bones or air
sinuses can spread to the subdural space
subdural empyema may produce a mass
effect.
thrombophlebitis may develop in the bridging
veins that cross the subdural space, resulting in
venous occlusion and infarction of the brain.
CLINICAL MANIFESTATIONS
SPINAL EPIDURAL ABSCESS
Four clinical stages have been described:
1. Fever and focal back pain;
2. Nerve root compression with nerve root
pain; “shooting pain”
3. Spinal cord compression with
accompanying deficits in motor/sensory
nerves, bowel/bladder sphincter function;
4. Paralysis (respiratory compromise may also
be present if the cervical cord is involved).
Armstrong, ID, Mosby inc,2000
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PREVENTION
Meningitis- Prevention
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Chemoprophylaxis for close contacts of index case if
Neisseria; treat contacts less than 4 years of age if H.
flu
Vaccinate all children, especially those at risk or those
with asplenia
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H. flu
S. pneumo- 7 valent up to 2 years, then 23 valent vaccine
Neisseria- quadrivalent vaccine (A, C, Y, W-135) for high
risk patients (asplenia, college age, military) over 2 years of
age
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Does not cover group B, which causes close to ½ of cases in US
Ventricular shunt infections
Intraventricular dose for shunt
infections
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ENCEPHALITIS
Encephalitis
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Viral
 HSV
 Arboviruses
 VZV, CMV, EBV, HIV, rabies
 Enteroviruses
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Bacterial
 Listeria monocytogenes
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Tick-borne illnesses
 RMSF: Rickettsia rickettsii
 STARI: Borrelia lonestari
 Lyme: Borrelia burgdorferi
 Ehrlichiosis: Ehrlichia chaffoensis
HSV Meningitis
K Tyler (USA)
CSF in HSV Encephalitis vs. Meningitis
Encephalitis
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Meningitis
WBCs/mm3
202 (2-667) 484 (58-1888)*
<10 cells/mm3 19%
12%
% Lymphs
76 (16-97)
87 (43-100) ns
RBCs/mm3
2518 (0-27,566) 54 (0-711) ns
Protein mg/dL 73 (22-146) 129 (75-281)*
Simko et al., CID 35:417, 2002
HSV Encephalitis
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2-4 cases/million people/year
Acute infection or more commonly reactivation of latent
infection (trigeminal nerve ganglion)
Characteristic site of damage: temporal lobe
 MRI findings of necrosis in temporal lobe
 Necrosis = RBC s on CSF!
30% Mortality with treatment
70% mortality without treatment
Definition of Recurrent
Meningitis
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>2 episodes meningitis
Symptom-free intervals
Normal CSF between episodes
Must be differentiated from chronic
meningitis
Culture + versus “Aseptic”
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BRAIN ABSCESS
MICROBIOLOGY OF BRAIN ABSCESS
AGENT
FREQUENCY (%)
Streptococci (S. intermedius, including S. anginosus)
60–70
Bacteroides and Prevotella spp.
20–40
Enterobacteriaceae
23–33
Staphylococcus aureus
10–15
Fungi *
10–15
Streptococcus pneumoniae
<1
Haemophilus influenzae
<1
Protozoa, helminths † (vary geographically)
<1
*Yeasts, fungi (Aspergillus Agents of mucor Candida Cryptococci
Coccidiodoides Cladosporium trichoides Pseudallescheria boydii)
†Protozoa, helminths (Entamoeba histolytica, Schistosomes Paragonimus
Cysticerci)
CTID,2001
Frontal abscesses
When to aspirate ?
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If single or multiple ring-enhancing lesions are found,
the patient should be taken urgently to surgery. All
lesions greater than 2.5 cm in diameter should be
excised or stereotactically aspirated and specimens
sent to the microbiology and pathology laboratories
(see earlier paragraphs). For abscesses in the early
cerebritis stage or when the abscesses are 2.5 cm in
diameter or less, the largest lesion should be aspirated
for diagnosis and organism identification
Empirical therapy of brain abscess
T. Gondii Encephalitis
Most Common Pathogens
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Otitis media, mastoiditis Streptococci
Paranasal sinusitis Streptococci
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Pulmonary infection Strep, Actionomyces
Dental Mixed, Bacteroides spp.
CHD  Strep
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Penetrating/Post-crani  S. aureus
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HIV  Toxoplasma gondii
Transplant  Aspergillus, Candida
TREATMENT
•Aspiration Or Open Drainage
•Empirical Combination
Antimicrobial Therapy
•Duration: 6 to 8 wks IV
•Prophylactic Anticonvulsant Therapy
•Glucocorticoids( Severe Edema & ICP )
•Serial CT-Scan or MRI