Transcript Meningitis and Encephalitis in the Older Patient

Meningitis and
Encephalitis in the Older
Patient
Debra Bynum, MD
Division of Geriatric Medicine
University of North Carolina Chapel Hill
April 2007
Outline
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Cases for thought…
Meningitis and Encephalitis: general features and
causes
Diagnosis: review of CSF findings
Meningitis: specific causes
Encephalitis: specific causes
Zoom in on important arboviruses and tick-borne
illnesses
Summary of diagnosis and treatment
Review of the cases
Cases
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1. Active 78-y/o man with prior hx of aortic valve
replacement years ago, presents with fever, slight
confusion, dehydration. Initial concern for SBE, but
CSF :TNC of 20. His serum Na 128. All cultures
negative. What would the DDX include?
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2. 85-y/o with severe dementia admitted with fever,
?stiff neck and worsening confusion and lethargy. CXR
and U/A are negative. What would you do?
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3. Healthy community living 75-y/o presents with
personality changes, confusion, agitation. She has no
fever, no other evidence of infection. What to do?
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4. 80-year-old man presents with low grade fever and
coma after several days of myalgias and viral-like
illness. Exam is notable for some Parkinsonian type
features… initial concern would be for ?
Meningitis
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Inflammation of the meninges
Classic triad:
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Fever
Headache
 Severe, frontal, photophobia, n/v
 Jolt accentuation
Meningismus/altered mental status
Meningeal signs
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Kernig sign: one leg with hip flexed, pain in back
with extension of knee
Brudzinski sign: flexion of legs and thighs when
neck is flexed
Encephalitis
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Inflammation of the cerebral cortex
Fever, HA, altered mental status
Key: early mental status changes
More commonly viruses
Obtundation/coma
Behavioral or speech problems, neurological signs,
seizures
Meningoencephalitis
Difference from meningitis: less likely fever, more
likely personality/behavioral changes
Causes of Meningitis
Bacterial
 Viral
 Fungal: cryptococcus
 Mycobacteria: MTB
 Parasitic/protozoa: Naegleria fowleri
 Noninfectious
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Medications
 Paraneoplastic
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Acute Bacterial Meningitis
Streptococcus pneumoniae
 Neisseria meningitidis
 Listeria monocytogenes
 Haemophilus influenzae: nearly unheard
of since vaccinations
 Less common: Gram negatives
(Klebsiella, E. coli)
 History of procedure: Staphylococcus
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Viral Meningitis
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Aseptic meningitis
Spectrum with encephalitis, meningoenchephalitis
Enteroviruses
HSV
VZV
Arboviruses (arthropod borne viruses)
 West Nile, Eastern Equine, Western Equine,
St. Louis, California, Japanese Encephalitis
HIV
Rabies virus
Adenovirus
CMV, EBV
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
Meningitis in the Elderly
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Decreased total incidence; increased in elderly
Increased prevalence of Listeria (25%)
30-50%: S. pneumoniae
Less likely Neisseria and Haemophilus
Less likely fever and meningeal signs; more likely
neurological symptoms, seizure, coma
More often complicated by pneumonia
Older patients with neurological impairment: 50%
mortality
Meningitis
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Risk Factors
 Age (bimodal peak)
 Prior neurosurgery, alcoholism, malignancy,
steroids, HIV, sinusitis, DM
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Clinical suspicion
 Triad: fever, nuchal rigidity, altered mental status:
only seen in 40% elderly
 Only 59% of elderly patients with acute bacterial
meningitis had fever
 Most have at least ONE symptom
The Diagnosis
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LP if suspicion
Do not delay antibiotics if suspected!
CT prior to LP in patients with focal neurological
deficits, seizures, HIV, or elderly
MRI: to identify areas of CNS involvement
 Temporal involvement with HSV
 Basilar meningitis with TB
The Lumbar Puncture: Risks
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Headache: 10-25%
 Typical: appears suddenly upon standing
 Decrease CSF pressure with small leak
 Decrease risk: small (<20 g) needle, leave patient
prone after procedure
 Blood patch
Infection (small)
Local bleeding: traumatic tap to epidural hematoma
Brain herniation
The LP
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Opening Pressure
 Important data
 Only in lateral decubitus (not position usually done
under radiology)
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Xanthochromia
 Yellow/orange color of centrifuged CSF
 RBC lysis – oxyhemoglobin, bilirubin
 Blood in subarachnoid space at least 2-4 hrs
 More likely due to blood in CSF and less likely
traumatic tap
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
increased
Cell type
Protein
50-80
mg/dL
>200
Nl/slight
increase
Nl/slight
increase
Increase
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: 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
Meningitis: Specific Causes
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
Listeria
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Food-borne outbreaks
Herd animals
Common, likely cause of mild GI illnesses
Invasive disease with bacteremia and CNS involvement
may follow other GI infection (piggy back…)
Increased risk with depressed cellular immunity:
pregnant women, elderly, AIDS, lymphoma, steroid
use, transplant patients
Listeria…
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Small, anaerobic gm + baccillus
Look like diphtheroids, contaminants
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
 Usually due to bacteremia
 Concomitant meningitis in 25-40% (rare with other
causes of brain abscess)
Listeria… Big Points
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NOT uncommon in elderly
Meningitis, encephalitis, focal brain abscess
Add Ampicillin
Diphtheroids in CSF: listeria unless proven otherwise
TB Meningitis
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Tuberculous meningitis (most common)
Intracranial tuberculomas
Spinal tuberculous arachnoiditis
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Meningitis: inflammation from rupture of
subependymal tubercle into subarachnoid space
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Basilar meningitis, CN palsies, hydrocephalus
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Subacute or chronic
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Initial neutrophilic pattern on CSF
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Very high CSF protein may be seen
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AFB smears often neg; need HIGH volume sent to lab
Viral Meningitis
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Aseptic meningitis
May be difficult to initially separate from partially
treated bacterial meningitis (obligates empiric
treatment for bacterial)
Differentiate from true aseptic (drug related such as
NSAIDs, paraneoplastic)
Viral Meningitis
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Finland study: etiology found in 66% patients with
aseptic meningitis
Viral encephalitis: etiology only found in 36% cases
Viral prodrome, sore throat, myalgias, ill contacts, GI
complaints; summer/fall season
Most common= enteroviruses (25%)
 Echoviruses
 Coxsackievirus
Viral Meningitis
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Less common causes
 Adenoviruses: URI sxs, year round
 CMV, EBV, HIV, influenzae
 Measles, mumps, rabies, rubella, varicella
 ?future avian flu (usually not CNS sxs, more
URI/pneumonia/ARDS and DIC)
Encephalitis: Specific Causes
Encephalitis Lethargica…
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The Awakenings…
1916: von Economo described CNS disorder with
lethargy and Parkinsonian features following viral
syndrome with pharyngitis
1916-1927 epidemic; now sporadic cases
1918: influenza pandemic, ?connection (?immune
mediated process)
Encephalitis
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More likely to be viral
Etiology only found in 35% cases
 HSV-1: 10% cases (but accounts for over 50%
cases in patients over 50)
 HSV-2
 VZV (?up to 10% in some series)
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Tick or insect borne diseases: 10%
Encephalitis
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Acute Viral Encephalitis
 Direct viral infection of neuronal cells
 Perivascular inflammation
 Destruction of gray matter
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Post-Infectious Encephalomyelitis
 Follows viral or bacterial infection
 Demyelination of white matter
 ?autoimmune component triggered by infectious
agent
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!
HSV Encephalitis
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Dysphasia, bizarre behavior, seizures
Abnormal EEG
High mortality: 30% with treatment
Survivors: 10% long term disability
Fever +/Treatment: Acyclovir (60-75% mortality without
treatment)
HSV Encephalitis: Big Points
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Odd behavior, think encephalitis
If thinking encephalitis, add acyclovir
RBCs on CSF (with xanthochromia or lack of clearing
between tube 1 and 4), think HSV
Temporal symptoms
Temporal necrosis or abnormalities on MRI
Arboviruses and Encephalitis
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Arbovirus: Arthropod Borne Virus
RNA viruses transmitted by mosquitoes or ticks
10 % cases of sporadic encephalitis (?higher in elderly,
up to 50% cases during epidemics)
Arboviruses and Encephalitis
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Alphavirus family:
 Eastern Equine Encephalitis **
 Western Equine Encephalitis
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Flavivirus family:
 St Louis Encephalitis **
 Japanese Encephalitis
 California Encephalitis
 West Nile Virus **
West Nile Virus and
Encephalitis in the Elderly
West Nile Virus
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1937: West Nile district Uganda (mild cases)
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Middle east/ Israel (14% fatality)
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1996: outbreak in Romania (4% fatality)
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1999: NY outbreak (11% fatality)
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Subsequent west spread to most states
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2002: 4156 reported cases in US, 284 deaths
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2003: 9858 cases, 262 deaths
West Nile Virus
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Season: summer
Mosquito transmission (currently infects 43/ 174
different types of North American mosquitoes)
Other routes
 Placenta
 Lactation
 Transfusion
 Organ transplant
West Nile Virus
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Disease of the elderly
Higher mortality in elderly
Other risk factors not clear (?maybe HTN and DM
leading to better virus entry)
WNV: Predictors
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Admission diagnoses:
 30%: aseptic meningitis
 15%: fever
 18%: viral infection
 14%: UTI
 10% pneumonia
 7% : encephalitis
 5%: probable WNV (year 2001)
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Mortality rates highest with:
Initial diagnosis of encephalitis (35% of those who died),
No headache (50% had HA, 7% those that died had HA),
and
Initial mental status changes
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WNV
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Presenting symptoms
 HA, fever, mental status changes
 CN findings, optic neuritis
 Myoclonus
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Flaccid Paralysis
 With or without encephalitis
 Asymmetric weakness/paralysis, no sensory loss
 Anterior horn cells (polio like)
 Absent DTRs
WNV
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Movement Disorders
Parkinsonian
 Tremors
 Bradykinesia
 Cogwheel rigidity
 Postural instability
 Masked facies
 80-100% will have rest or intention tremor
 30% will have myoclonus
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WNV: Diagnosis
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High index of suspicion
CSF: usually 200 TNC; 5-10% can have over 500 TNC,
5% with < 5 TNC
CSF with 50% neutrophils
Elevated CSF protein
CSF for ab studies: anti WNV ab, and negative SLE
IgM (up to 40% cross reactivity in earlier studies)
WNV: Treatment
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?nucleoside analogues (ribavirin – no benefit in Israel)
Human Immunoglobulin : protective antibodies
(patients from Israel with high titers of anti-WNV ab);
if effective, only in early disease
?vaccine development (effective in horses in 2001)
?inactivated JEV vaccine?
Meningitis and Encephalitis:
Others
Tick-Borne Diseases
RMSF **
 Lyme Disease **
 Ehrlichiosis **
 STARI **
 Tularemia
 Babesiosis
 Colorado Tick Fever
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Rocky Mountain Spotted Fever
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Rickettsia rickettsii
 Gm negative intracellular bacteria
 Endothelial cells: small vessel vasculitis
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Southeast, summer
Dog Tick, Wood Tick
2nd most common tick-borne illness
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Fever/headache/nausea/rash 80%
Rash: blanching maculopapular, palms/soles,
spreads centrally, later petechial and purpuric
Hyponatremia, thrombocytopenia, inc ALT
CSF: inc TNC, inc protein; neg gram stain
RMSF: Diagnosis
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Clinical suspicion
Low threshold to empirically treat
Rash may be absent in 20%
RMSF serologies: initial may be negative; need
convalescent titers several weeks later
RMSF: Treatment
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Doxycycline 100 BID
Do not delay
?newer quinolones: probably, but no studies and no
recommendations
No indication for prophylactic treatment after
uncomplicated tick bite
Prevention: frequent inspection
RMSF: Big Points
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Empiric Treatment if even suspected
In North Carolina, any fever, HA, neuro syndrome will
need treatment
First serology titers NOT reliable
Hyponatremia, low platelets, elevated LFTs, think
RMSF…
Do not wait for the rash…
Lyme Disease
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Borrelia burgdorferi
Deer Tick (smaller)
NE/Great Lakes, but reported in almost all
Stages
 1: erythema migrans rash, viral-like syndrome
 2. early disseminated phase, secondary cutaneous
 3. late/chronic: arthritis, cns involvement (CN
palsies), myocardial damage
STARI
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Southern Tick Associated Rash Illness
Lyme-like infection in North Carolina with negative
Lyme serologies
Lone Star Tick
Borrelia lonestari
Ehrlichia
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“Rashless” RMSF
 Fever, headache
 CSF: pleocytosis, neg gm stain, inc protein
Hyponatremia, thrombocytopenia, elevated LFTs
Lone Star tick, Dog Tick
Same treatment as RMSF
Serologies and convalescent titers
Overall Picture: Diagnosis
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Difficult to initially separate meningitis from
encephalitis in elderly; both present with mental
status changes; elderly with meningitis less likely to
have fever
Other infections cause delirium in elderly
Red flags
 Any CNS focality
 Behavioral changes/personality changes
 Seizures
 Lack of other source of infection
 Headache, ? nuchal rigidity, ill contacts
 Season, outdoor activity
 Low threshold to do LP
Overall Picture
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Main Players
 Strep pneumoniae
 Listeria
 Viral agents such as enteroviruses
 HSV
 Arboviruses (including WNV now)
 Tick-borne bacteria (RMSF, ehrilchia, STARI)
If things are not adding up…
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Less common causes
 VZV
 Rabies virus
 Post-measles, mumps, cmv, ebv
 Adenoviruses
 TB
 Protozoa
 Cryptococcus
 Gm negatives: klebsiella, e coli
Diagnosis
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CSF
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Elevated protein least specific
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Acute bacterial meningitis usually has high TNC,
low glu, unless partially treated or listeria
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More than 2-3 TNC is not normal
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Gram stain, culture, PCR for HSV, viral studies for
enteroviruses, serologies for arboviruses
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Latex agglutination studies: NOT helpful
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Serum for RMSF/ehrlichiosis titers: initial and
convalescent titers
Treatment
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Initial empiric treatment
OK to shotgun pending culture and test results the
first 24 - 48 hours!
Risk of s. pneumoniae resistance and high mortality of
untreated disease – vancomycin initially
Treatment: Dexamethasone
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Acute bacterial meningitis
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Decreased mortality/morbidity (20 min prior to abx)
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Recommended: proven S. pneumoniae, high
opening pressure, pos gm stain
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Not clear with other causes, subgroups like elderly
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Probably not bad effects with viral causes
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Dose: .4 mg/kg Q 6 hrs for 2-4 days
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?decrease vancomycin crossing blood-brain barrier
Treatment Summary
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Vancomycin
Ceftriaxone/cefotaxime
Ampicillin
Acyclovir
Doxycycline
?dexamethasone
OK to cover for all for first 24-48 hours, then narrow
based upon CSF results and serologies
CASES
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1. Active 78-y/o man with prior hx of aortic valve
replacement years ago, presents with fever, slight
confusion, dehydration.
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Initial concern for SBE, but CSF :TNC of 20.
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His serum Na 128. All cultures negative.
What would the DDX include?
CASES
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2. 85-y/o with severe dementia admitted with fever,
?stiff neck and worsening confusion and lethargy.
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CXR and U/A are negative.
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What would you do?
CASES
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3. Healthy community living 75-y/o presents with
personality changes, confusion, agitation.
She has no fever, no other evidence of infection.
What to do?
CASES
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4. 80-year-old man presents with low grade fever and
coma after several days of myalgias and viral like
illness.
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Exam is notable for some Parkinsonian type features…
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initial concern would be for ?