Transcript Meningitis - University of Ottawa

Meningitis
Sydnee Burgess, PGY1
99 topics, Department of Family Medicine
University of Ottawa
CFPC objectives: key features
• In the patient with a non-specific febrile illness, look for meningitis,
especially in patients at higher risk (eg: immunocompromised, alcoholism,
recent neurosurgery, head injury, recent abdominal surgery, neonates,
aboriginal groups, students living in residence)
• When meningitis is suspected ensure a timely lumbar puncture
• In the differentiation between viral and bacterial meningitis, adjust the
interpretation of the data in light of recent antibiotic use
• For suspected bacterial meningitis, initiate urgent empiric IV antibiotic
therapy (ie, even before investigations are complete)
• Contact public health to ensure appropriate prophylaxis for family, friends
and other contacts of each person with meningitis
CFPC objectives: key features
• In the patient with a non-specific febrile illness, look for meningitis,
especially in patients at higher risk (eg: immunocompromised,
alcoholism, recent neurosurgery, head injury, recent abdominal surgery,
neonates, aboriginal groups, students living in residence)
• When meningitis is suspected ensure a timely lumbar puncture
• In the differentiation between viral and bacterial meningitis, adjust the
interpretation of the data in light of recent antibiotic use
• For suspected bacterial meningitis, initiate urgent empiric IV antibiotic
therapy (ie, even before investigations are complete)
• Contact public health to ensure appropriate prophylaxis for family, friends
and other contacts of each person with meningitis
Looking for meningitis
• Risk factors:
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immunocompromised,
alcoholism,
recent neurosurgery,
head injury,
recent abdominal surgery,
Infectious contacts: neonates,
• aboriginal groups, students living in residence
• Infections (ENT or other like infective endocarditis),
In Family Medicine
notes it says liver
diseases and
others… don’t
know where that’s
from… not seen in
said sources
Case
• 18 F lives in a dorm, presents for one day of fever and woke up with a
stiff neck that felt awful when she was on the ride over here.
• Risk factors for meningitis?
• Whats most sensitive in her symptoms that to point to meningitis?
Looking for meningitis
• The classics…
• Infants: ↑or ↓ in T⁰, irritability/inconsolable crying, lethargy, seizures, poor
feeding, V⁰/D⁰, bulging anterior fontanelle, jaundice
• Children/adults: F ⁰, severe h/a, stiff neck +- back pain +- (+ Kernig and
Brudzinski) photophobia. N⁰/V⁰, loss of balance seizures, disorientation,
confusion, ∆LOC, CN palsies, ↑ICP signs (eg papilledema), +- signs of cerebral
infarct
• Or… sepsis, septic shock
• Petecchiae in meningococcal +- s. pneumoniae and other
Looking for meningitis
• Signs and symptoms: the evidence…
• No fever , or
No meningitis (se 99-100%)
• no neck stiffness, or
• no altered mental status
• (Fever + h/a) + jolt accentuation ↑ +LR 2.2 (-LR 0) se 100% sp54%
• Meningitis > encephalitis:
• Normal brain function (uncomfortable, lethargic, distracted by h/a)
• Encephalitis: altered mental status, motor/sensory deficits, altered
behaviour and personality, speech or movement disorders
• Contiguous structures so/and can have overlapping features
Case:
• A worried mother brings in her 6 month old baby saying that he has
not been himself lately. The baby seems tired, only looking around
briefly when you talk him and cries a bit and pulls away his hand
when you pinch his finger.
• What’s this baby’s GCS?
Pediatric GSC
(answer: 10)
CFPC objectives: key features
• In the patient with a non-specific febrile illness, look for meningitis,
especially in patients at higher risk (eg: immunocompromised, alcoholism,
recent neurosurgery, head injury, recent abdominal surgery, neonates,
aboriginal groups, students living in residence)
• When meningitis is suspected ensure a timely lumbar puncture
• In the differentiation between viral and bacterial meningitis, adjust the
interpretation of the data in light of recent antibiotic use
• For suspected bacterial meningitis, initiate urgent empiric IV antibiotic
therapy (ie, even before investigations are complete)
• Contact public health to ensure appropriate prophylaxis for family, friends
and other contacts of each person with meningitis
• When do you ask for a LP, what do you ask for?
Lumbar puncture in suspected meningitis
• When: asap…
• When don’t you do an LP?
Lumbar puncture in suspected meningitis
• when not:
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as previous, and…
Shock
Infection at LP site
Bleeding disorders
• Other reasons for CT scan before LP (some evidence for)
• Underlying neuro condition
• Immunodeficiency states
• >60 yo
Lumbar puncture in suspected meningitis
• What do you ask for in an LP?
Lumbar puncture in suspected meningitis
CFPC objectives: key features
• In the patient with a non-specific febrile illness, look for meningitis,
especially in patients at higher risk (eg: immunocompromised, alcoholism,
recent neurosurgery, head injury, recent abdominal surgery, neonates,
aboriginal groups, students living in residence)
• When meningitis is suspected ensure a timely lumbar puncture
• In the differentiation between viral and bacterial meningitis, adjust the
interpretation of the data in light of recent antibiotic use
• For suspected bacterial meningitis, initiate urgent empiric IV antibiotic
therapy (ie, even before investigations are complete)
• Contact public health to ensure appropriate prophylaxis for family, friends
and other contacts of each person with meningitis
LP results: viral?bacterial?bacterial with atb?
• Often not possible to differentiate bacterial from viral purely based on
LP
• ↑ probability of bacterial:
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↑ WBC ↑ neutro (not so elevated in the beginning) >=500/µL
↓ glucose
N↑ protein
+ Gram stain (80-90%) if hematogenous infection… depends on pathogen
• Gold Standard: +ve culture…. Won’t be if previous atb
• If +CSF and –ve culture: consult ID  PCR (latex agglutination = poor
se and sp)
Bacterial or viral
Bacterial or viral?
Protein 100 mg/dL
Glucose 1.7mmol/L
WBC count 1200 x 106/µL
Bacterial or viral?
Protein 0.55 mg/dL
Glucose 3mmol/L
WBC count 600 x 106/µL
Bacterial or viral?
Protein 0.49 mg/dL
Glucose 1.5 mmol/L
WBC count 600 x 106/L
• “If you do an LP within 4 hours of antibiotics you’re good”
• complete sterilization of meningococcus within 2 hours and the
beginning of sterilization of pneumococcus by 4 hours into therapy
LP results: viral?bacterial?bacterial with atb?
-Procalcitonin…
-Enterovirus…
- lactate
But really…
• If bacteria are seen on Gram stain, it helps diagnose bacterial
meningitis but if this test is negative, bacterial meningitis cannot be
ruled out.
• On top of an LP and a CT, what other investigations might you need?
Additional tips on your approach
• Blood:
• Culture
• Glucose to compare to CSF glucose
CFPC objectives: key features
• In the patient with a non-specific febrile illness, look for meningitis,
especially in patients at higher risk (eg: immunocompromised, alcoholism,
recent neurosurgery, head injury, recent abdominal surgery, neonates,
aboriginal groups, students living in residence)
• When meningitis is suspected ensure a timely lumbar puncture
• In the differentiation between viral and bacterial meningitis, adjust the
interpretation of the data in light of recent antibiotic use
• For suspected bacterial meningitis, initiate urgent empiric IV antibiotic
therapy (ie, even before investigations are complete)
• Contact public health to ensure appropriate prophylaxis for family, friends
and other contacts of each person with meningitis
Bacterial: empiric ATB
• IV
• Don’t delay for LP if LP not available (eg: CT scan interim):
• Each hour of delay = ↑ 30% mortality or disability in adults
• Re-evaluate and modify atb when csf gram stain, culture and
antibiogram come back
Bacterial: empiric ATB… what to use
Bacteria
<6wk
GBS
E coli
Listeria monocytogenes
(rarely, crossover pathogens)
Enterobacteriaceae
Empiric Antibacterial
Regimen
Ampi +Cefo
+ genta if GBS suspected
(rarely, crossover pathogens)
Age group
6wk-3months
GBS
S. pneumoniae
N. meningitides
HiB
Ampi + ceftri (or cefo)
+ vancomycin
>3months-50 yo
S. pneumoniae
N. meningitidis
HiB
Ceftri (or cefo)
+ vancomycin
>50 yo or alcoholics
E coli
S. pneumoniae
N.meningitidis
Listeria monocytogenes
Ampi + Ceftri (or cefo)
+ vancomycin
(give cephalo before vanco to
ensure initial broad coverage
and penetration into CSF)
1) give Ampi, Ceftri/Cefo and Vanco
2) Under 6 weeks, no vanco. And genta if GBS is suspected
3) No ampi from 3months-50 years old.
Bacterial: empiric ATB… what to use
Risk factor
Bacteria
Empiric Antibacterials
CSF leak (basilar skull facture)
Some with staph, some with
pseudomonas…. But really, the
treatment doesn’t change.
3rd gen cephalosporin
+ vanco
+Listeria monocytogenes
+ ampicillin
Penetrating head
trauma/neurosurgery
Ventriculoperitoneal shunt
Asplenia (anatomic or function
Humoral immune deficiency states
(agammaglobulinemia)
Cellular immune deficiency states
(chemotherapy, HIV)
Doses
• Gentamycin:
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Neonates <1.2kg: 2.5mg/kg q 8-12h
1.2-2kg: 2.5mg/kg q 12h
>2kg: 2.5mg/kg q8h
Adults: 1-2mg/kg q 8h
• Cefotaxime
• Neonates ≥ 7d:
• 1.2-2kg: 150mg/kg/d divided q 8h
• ≥ 2kg: 150-200mg/kg/d divided q6-8h
• Neonates <7d:
• <2kg: 100mg /kg/d divied q 12h
• ≥ 2kg: 100-150mg/kg/d divided
• 6wk-12y: 300mg/kg/d divided q 6h
• >12 y: 2g q-6h (max: 12g/d) q 8h
Doses
• Ceftriaxone
• Infatnts and children:
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100mg/kg q 12h x 3doses, then q 24h
• Adults
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2g q 12h-2h (max g/day)
• Vancomycin:
• Neonates:
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>2kg or PCA >37 weeks: 22.5mg/kg/dose q 12h
• Infants >4 weeks and children:
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60mg/kg/day divided q 6h (max 1g/dse or 4g/day prior to therapeutic monitoring)
• Adults: 15-20mg/kg q 8h-12h
• Ampicillin
• Neonates ≤7 days: ≤ 2kg: 100mg/day divided q12h. >2kg:150mg/kg/day divided q8h. GBS: 200mg/kg/day divided q8h
• Neonates >7 days: <1.2kg: 100mg/kg/day divided q12h. 1.2-2kg: 150mg/kg/day. >2kg: 200mg/kg/day divided q6h. GBS: 300400mg/kg/day divided q4-6h.
• Older infants and children: 200mg/kg/day divided q4-6h. GBS: 400mg/kg/day divided q4h-6h.
• Adults 2g q 4h (max 12g/day)
….Then modify once you get your antibiogram
Modify your antibiotics…
… and duration of treatment depends on pathogen
Tx corticosteroids
• To ↓CNS inflammatory response→↓ neuro sequelae (hearing loss
and short term)
• Dexamethasone
• Potential for delayed sterilization of CSF (∆ drug penetration with vanco)…
theoretically
• Children: 0.6mg/kg/d / 6 doses x 2-d, before or with 1st dose of atb
• Consult ID for >6wk for risk and benefits…
• Steroids controversial except in HiB: decreases hering loss if given just before/ w/I 30 min
of atb
• Adults: lower mortality
• 10mg q6h x 4d
• Infectious disease society of America: 0.15mg//kg q 6hx 2-d
• Audiology assessment before d/c or w/I 1 month of d/c
Aseptic meningitis
• In the US, >10,000 cases reported annually, but actual incidence
probably ~ 75,000.
• Due to uneventful clinical outcome of most cases and the inability of some
viral agents to grow in culture.
• prognosis : usually excellent, with most cases resolving in 7-10 days.
Exception: neonates
Aseptic meningitis
• Dx difficult because of large variety of potential agents and overlap with
bacterial
• Note opening CSF
• specific antigen or nucleic acid tests for viruses (as well as culture for bacteria)
• At risk patients (elderly, immunocompromised, received antibiotics prior to
presentation) = empiric therapy for 48hr
• Otherwise observe patient w/o atb
• If HIV suspectd, blood test for HIV RNA and HIV antibody
• If HSV suspected (eg: concomitant genital lesion), empiric Acyclovir
(10mg/kg IV q 8h)
• If unclear viral/bacterial: empiric atb after BCx and CSF Cx
• or observe and repeat LP in 6-24hrs
Aseptic meningitis
• Etiology (hx= clues):
• Most common: enterovirus. HSV, 1 and 2, HIV
• Mycoacteria (tb), fungi (Cryptococcus, coccidioides), spirochetes, parasites
(angiostrongylus)
• Parameningeal infections
• Medications (NSAIDs, TMP-SMX, IvIG, cetuximab, antiepilectic drugs OKT3
antibodies
• Malignancy (large cell lymphomas ,acute leukemias, carcinomatosis)
• LCMV (rodent exposure), tic borne (Lyme/ Borrelia Burgdorferi, RMSP,
ehrlichiosis), mumps, syphilis
Aseptic meningitis: fun facts off medscape
• currently, more than 85% of viral meningitis cases are caused by
nonpolio enteroviruses.
• oral-fecal route, but can also spread through the respiratory route.
• Mumps, polio, and lymphocytic choriomeningitis viruses (LCMVs) are
now rare offenders in developed countries.
• in as many as one third of cases, no causative agents are identified
Aseptic meningitis: fun facts off medscape
• Partially treated dissemnitaed ENT infections (OM, sinusitis) can give an aseptic picture
• Lyme meningitis has a predilection to cause focal cranial nerve palsies, with the seventh nerve
most commonly affected.
SAMP !
• You are seeing a 12 day old infant with suspected meningitis in the ER
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What are the most likely causative organisms? (list 2)
How would you confirm the diagnosis? (list 2)
What are two appropriate treatment regimens?
If the child was 5 months instead, what would the causative agents be? (list 2)
What are two contraindications to LP?
What treatment should be initiated?
The patient has a 2 yr old brother at home. How would you treat his brother?
CFPC objectives: key features
• In the patient with a non-specific febrile illness, look for meningitis,
especially in patients at higher risk (eg: immunocompromised, alcoholism,
recent neurosurgery, head injury, recent abdominal surgery, neonates,
aboriginal groups, students living in residence)
• When meningitis is suspected ensure a timely lumbar puncture
• In the differentiation between viral and bacterial meningitis, adjust the
interpretation of the data in light of recent antibiotic use
• For suspected bacterial meningitis, initiate urgent empiric IV antibiotic
therapy (ie, even before investigations are complete)
• Contact public health to ensure appropriate prophylaxis for family,
friends and other contacts of each person with meningitis
Prophylaxis for contacts: post-exposure
• N meningitidis
• <1mo Rifampin 5mg/kg q 12 po x2d
• >1mo Rifampin 10mg/kg (max 600mg) q 12h x 2d
Contact Public
Health!, and…
• Or ceftriaxone 125mg IM x1 (<15 yo), 250mg IM x1 >15 yo
• (1st choice for pregnant women)
• Ciprofloxacin 20mg/kg (max 500mg) po x1
• HiB
• Rifampin 20mg/kg (max 600mg) po od x4d
• <1 mo: consult ID
• No prophylaxis for pregnant women (Rifampin CI)
• Index patient should receive prophylaxis prior to d/c to eradicate bacterial
carriage unless cefotaxime or ceftriaxone was used for tx
Prevention: routine immunization
• Hib, polio
• Strep pneumoniae (prevnar, pneumovax when old)
• Men-C in 2nd year of age (~1 week after 12mo birthday)
• Men-C-ACYW in Grade 7
Prevention
• Vaccines
• HiB S pneumoniae N meningitids part of all Canadian universal infant immunization programs.
• Herd effect evidenced
• Pneumococcal vaccine is >95% effective in preventing invasive disease fr the 7-valent vaccine used
in 2001-2005, and further reduction in 13-valent
• Conjugated meningococcal vaccine against N meningitides type C >90% effective against invasive
infection (Meningitec, Menjugate, Nes Vac-C): 1 dose in 2nd year of life (at 12months). If at
increased risk, at 2, 4, and 12 months and an adolescent booster.
• At risk:
• Asplenia, primary antibody deficiency disorder, cellular immunodeficiency (complement, properdin or factor D
deficiency), traveller’s to high risk areas, lab personnel with exposure to meningococcus, the military
• Meningococcal types A, C, W, Y-135 (Menactra, Menveo) for high risk individuals over the age of 2
yo (impact unknown yet) and HIV positive children + an adolescent booster.
• Utility of boosters after 12 yo is unknown
• Type B (4CMenB. Bexsero) now available for indivuals 2mo-17 yo, not recommended for routine
admin, but for high risk (asplenia, sickle cell disease, complement deficiency, close contacts of
Men type B
Prevention: the traveller
Prevention: the traveller
• Endemic areas the African Meningitis Belt
SAMP!!
• A 4 year old boy presents with a 3 day history of a “cold” and
increasing lethargy. Now he has a fever. On exam, he appears to have
some neck stiffness.
• What other physical exam findings are important if you suspect meningitis?
List 3.
• What empirical medications would you put him on?
• What is the specific treatment for meningococcus? (name, route, dose,
duration)
• If an LP is performed, what 4 things would you ask the specifically for?
• What other lab tests would you order? List 4.
KEY POINTS…
• … and questions?
References
• Therapeutic Choices. Bacterial Meningitis
• Guidelines for management of suspected and confirmed bacterial
meningitis in over 1 month olds in Canada (Canadian Pediatric Society).
March 2014
• Aseptic Meningitis in Adults. Uptodate.com
• Sharon E Straus, Kevin E Thorpe, Jayna Holroyd-Leduc. How do I perform a
lumbar puncture and analyze the results to Diagnose Bacterial Meningitis?
JAMA: 200; 296 (16): 2012-2022. oi: 10.100.1/jama.296.16.2012
• Statement on Meningococcal Disease and the International Traveller.
McCrthy, Anne. Canada Communicable Disease Report CCDR: volume 1-05,
May 7 2015. ISSN 1481-8531