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Flashcards in Meningitis and Encephalitis Deck (76):
1

Inflammation/infection of the membranes surrounding the brain and spinal cord

Meningitis

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Acute inflammation/infection of brain parenchyma

Encephalitis

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Gram + cocci

Streptococcus pneumonia

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Gram - coccobacilli

Haemophilus influenzae

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Gram - cocci

Neisseria meningitidis

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Gram - bacilli

Gram negative bacteria (E.coli, Klebsiella, Pseudomonas)

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Gram + bacilli

Listeria monocytogenes

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Risk factors for Meningitis

Sickle cell anemia
Asplenic status
Cochlear implants
Head trauma
Immunosuppression
Mastoiditis, URT infection, Otitis media
Exposure to cigarette smoke
Alcoholism

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Incidence trend

Decreasing due to introduction of vaccines
Shift from young to adult population due to vaccines
1986: 4.9 cases per 100,000
1998: 2 cases per 100,000
2007: 1.4 cases per 100,000

Age Distribution
18 yrs: 20.8, 51.5

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Vaccines

Haemophilis influenza Type B (more virulent form; cause of epiglottitis)
S. pneumoniae
N. meningitidis

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Sequelae

MC after S. pneumo infections
~30% develop neuro sequelae
Sensorineural hearing loss
Hydrocephalus
Focal sensory motor defects
Seizure disorder
Death 2-30%, avg 20%

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Adheres to the skull

Dura mater

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Lies between the dural and pia maters

Arachnoid mater

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Lies directly over brain tissue

Pia mater

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Between arachnoid and pia mater; This becomes inflammed w/meningitis

Subarachnoid space
-CSF flows thru this space

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CSF flows thru this space

Subarachnoid space

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Where and how is CSF produced

Largely made by the choroid plexus in the lateral and fourth ventricle

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CSF flow

Unidirectionally, down the spinal cord

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CSF Amounts

Differ by age:
Infants: 40-60ml
Children: 60-100ml
Adults: 110-160ml

Important for determining different drug concentrations in the CSF for Tx

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Injecting drugs into the CSF cavity

Intrathecal

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Injecting drugs into ventricles

Intraventricular (Increased risk of increased endotoxin release into the CNS--not for meningitis tx)

MC for neurosurgery or shunt infections

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Factors that INCREASE penetration of abx into the CSF

Meningeal inflammation
Low molecular weight medication
Lipid soluble compounds (lipid bilayer)
Compounds that remain unionized at physiologic pH
Low protein bound medications

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Medications with therapeutic levels in CSF +/- Inflammatoin

Sulfonamides/Trimethoprim
Chloramphenicol (misc abx, not used often)
Rifampin
Metronidazole
Isoniazid, Pyrazinamide, Ethionamide (for TB)

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Medications with therapeutic levels WITH inflammed meninges

B LACTAMS:
Penicillin G
Nafcillin
Cefotaxime
Ceftriaxone
Ceftazidime
Imipenem
Meropenem
Vancomycin
Linezolid - VRE
Aztreonam - Gram - specialist
Ciprofloxacin
Fluconazole - Antifungal
Ganciclovir - Antiviral
Acyclovir - Antiviral

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Medications with NON-Therapeutic levels in CSF +/- inflammation

Aminoglycosides
First generation cephalosporins
Second generation cephalosporins (Except cefuroxime)
Clindamycin
Amphotericin - Antifungal

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Pathophysiology of Bacterial Meningitis
Sources of Infection

Contiguous spread: Sinusitis, otitis media, birth defects

Hematogenous: Bacteremia seeding meninges

Direct inoculatoin: Trauma, neurosurgical comps

Reactivation of latent disease: HSV, TB

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CNS response to infection

Contact w/bacterial cell wall components triggers cytokine release (TNF alpha, IL-1, PAF); Platelet activating factor (PAF) triggers clotting cascade, forming microthrombi; Cytokine cascade stimulated vasodilation and vascular permeability; Compromised BBB allows entry of neutrophils and other blood components --->CEREBRAL EDEMA -> Increased ICP --> Decreased cerebral blood flow --> Signs/sxs of meningitis AND Ischemic and direct tissue damage

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Signs/Sxs of Meningitis

HA, fever, neck stiffness, altered mental status, seizures, abnormal CSF findings
[Adults >65 have more muted signs/sxs]

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Diagnostic tests for meningitis

Lumbar puncture: CSF cell count, chemistries, gram stain, culture
Blood culture
Rapid diagnostic methods: Latex fixation, enzyme immunoassay, PCR

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CSF Findings

NORMAL: BACTERIAL MENINGITIS
WBC 80
Protein <60% SBG)
Gram stain 75-90%+

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Likely Meningitiis Pathogens in Age <1 month

Group B Streptococcus, E.coli, L.monocytogenes, Klebsiella species

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Likely Meningitis Pathogens in Age 1-23 months

S.pneumoniae, N. menigitidis, Group B Strep, H.flu, E. coli

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Likely Meningitis Pathogens in Age 2-50 yrs

N. menigitidis, S. penumoniae

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Likely Meningitis Pathogens in Age >50 yrs

S. pneumoniae, N meningitidis, L monocytogenes, Gram - bacilli (EKP)

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Treatment Goals

Eradicate infection: rapid initiation of Abx is importnat
Improve signs and sxs: analgesics, fluids, antipyretics
Prevent development of neurologic sequelae and survive

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See Management Algorithm for Adults w/Suspected Bacterial meningitis

Note: Do not delay abx start up if LP needs to be delayed (delayed abx leads to increased morbidity and mortality)

*It takes 12-24 hours to see changes in CSF after starting Abx (can still do a LP later within 24 hours)

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NEGATIVE CSF Gram Stain or Gram Stain NOT Available:
Age <1mo Common Pathogens

Group B Streptococcus
E. coli
L monocytogenes
Klebsiella sp

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NEGATIVE CSF Gram Stain or Gram Stain NOT Available:
Age <1mo Antimicrobial Therapy

Ampicillin + Cefotaxime
OR
Ampicillin + Aminoglycoside (synnergistic effect)

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NEGATIVE CSF Gram Stain or Gram Stain NOT Available:
Age 1-23 mo Common Pathogens

S. pneumo
N menigitidis
Group B strep
H flu
E coli

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NEGATIVE CSF Gram Stain or Gram Stain NOT Available:
Age 1-23 mo Antimicrobial Therapy

Vancomycin + 3rd Gen Cephalosporin (Cefotaxime or Ceftriaxone)

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NEGATIVE CSF Gram Stain or Gram Stain NOT Available:
Age 2-50 yrs Common Pathogens

N menigitidis
S penumoniae

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NEGATIVE CSF Gram Stain or Gram Stain NOT Available:
Age 2-50 yrs Antimicrobial Therapy

Vancomycin + 3rd Gen Cephalosporin (Cefotaxime or Ceftriaxone)

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NEGATIVE CSF Gram Stain or Gram Stain NOT Available:
Age >50 yrs Common Pathogens

S pneumoniae
N meningitidis
L monocytogenes
Gram - bacilli

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NEGATIVE CSF Gram Stain or Gram Stain NOT Available:
Age >50 yrs Antimicrobial Therapy

Vancomycin + Ampicillin + 3rd Gen Cephalosporin

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POSITIVE CSF Gram Stain

Gram + Diplococci

S. pneumoniae

Ceftriaxone or Cefotaxime + Vanco + Dexamethasone

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POSITIVE CSF Gram Stain

Gram - Diplococci

N meningitidis

Ceftriaxone or Cefotaxime

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POSITIVE CSF Gram Stain

G + Bacilli

L monocytogenes

Ampicillin +/- Gentamycin

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POSITIVE CSF Gram Stain

Gram - Bacilli

H flu, Coliforms, Pseudomonas aeruginosa

Ceftazidime or Cefepime +/-Gentamycin (All cover Pseudomonas)

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PATHOGEN IDENTIFICATION & SENSITIVITY KNOWN

Group B Strep (Gram + cocci)

Penicillin G or Ampicillin

Alt: Ceftriaxone or Cefotaxime

14-21 Days

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PATHOGEN IDENTIFICATION & SENSITIVITY KNOWN

H flu (Gram - bacilli)

Ceftriaxone

Alt: Chloramphenicol, Cipro, Aztreonam

7 Days

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PATHOGEN IDENTIFICATION & SENSITIVITY KNOWN

N meningitidis (Gram - diplococci)

Ceftraixone

Alt: Chloramphenicol

7 Days

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PATHOGEN IDENTIFICATION & SENSITIVITY KNOWN

L monocytogenes (Gram + bacilli)

Ampicillin +/- Gentamicin

Alt: TMP/SMX, Meropenem

>21 Days

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PATHOGEN IDENTIFICATION & SENSITIVITY KNOWN

S. pneumo (G + diplococci)
Pen MIC <0.1

Penicillin G or Ampicillin

Alt: Ceftriaxone or Chloramphenicol

10-14 Days

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PATHOGEN IDENTIFICATION & SENSITIVITY KNOWN

S. pneumo (G + diplococci)
Pen MIC 0.1-1

Ceftriaxone or Cefotaxime

Alt: Cefepime or Meropenem

10-14 Days

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PATHOGEN IDENTIFICATION & SENSITIVITY KNOWN

S. pneumo (G + diplococci)
Pen MIC >2

Vanco + Ceftriaxone (Or Cefotaxime)

Alt: Moxifloxacin

10-14 Days

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PATHOGEN IDENTIFICATION & SENSITIVITY KNOWN

S. pneumo (G + diplococci)
Ceftriaxone MIC >1

Vanco + Ceftriaxone (Or Cefotaxime)

Alt: Moxifloxacin; If Ceftriaxone MIC >2, Add Rifampin

10-14 Days

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Dexamethasone Rationale

The subarachnoid space inflammatory response during bacterial meningitis is a major factor contributing to morbidity and mortality; Attenuation of this inflammatory response may diminish many of the pathophysiologic consequences of bacterial meningitis

Dexamethasone=Steroid (decreases inflammation and the immune function)
-But...may decrease immune function and decrease ability to abx to cross BBB

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Adjunctive Dexamethasone in Bacterial Meningitis

Infants and Children w/ Haemophilus influenzae Type B Meningitis (only if started before abx)

Adults with pneumococcal meningitis (Only if started before abx)

Administer at 0.15mg/kg q6h for 2-4 days 15 minutes BEFORE or with first antimicorbial dose to help attenuate the increased inflammation after abx kills bacteria

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Who should receive meningitis prophylaxis?

Close contacts of patients with either H. flue or Neisseria meningitidis should receive prophylaxis

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H. flu prophylaxis

Rifampin 600mg PO q24h x 4days

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Neisseria meningitidis prophylaxis

Ceftriaxone 250mg IM x1
Rifampin 600mg PO q12h x4 doses or
Ciprofloxacin 500mg PO x1 (if not resistant)

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Viral Encephalitis Etiology

Enteroviruses (85%) - MC
Arboviruses (St. Louis, La Crosse, West Nile)
Adenoviruses
HSV
HIV
Influenza
Cytomegalovirus

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Viral Encephalitis Clinical Presentation

HA
Mild fever
Nuchal rigidity +/-
Malaise
Photophobia
Decreased LOC
Rash (West Nile)
Nausea
Vomiting

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Viral Encephalitis Clinical Course

Most are self limiting (1-2 wks duration)
West Nile and HSV associated with significant morbidity and mortality

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Viral Encephalitis Treatment: Enteroviral

Supportive care: Fluids, antipyretics, analgesics

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Viral Encephalities Tx: West Nile

Supportive care
Anti-seizure medication if needed
Tx for increased ICP as needed

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Viral Encephalitis Tx: HSV

Supportive care
Anti-seizure medications
Acyclovir: 10mg/kg IV q8h for 2-3 weeks (adults)

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CNS Infection Tx Dosing:
Acyclovir

Adult: 10mg/kg IV q8h

Peds: 20mg/kg IV q8h

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CNS Infection Tx Dosing:
Ampicillin

Adult: 2gm IV q4h

Peds: 75mg/kg IV q6h

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CNS Infection Tx Dosing:
Cefotaxime

Adults: 2gm IV q4-6h

Peds: 75mg/kg IV q6-8h

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CNS Infection Tx Dosing:
Ceftriaxone

Adults: 2gm IV q12-24h

Peds: 100mg/kg IV q24h

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CNS Infection Tx Dosing:
Penicillin G

Adults: 4MU IVq4h

Peds: 0.05 million units/kg IV q4-6h

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CNS Infection Tx Dosing:
SMX/TMP

Adults: 5mg/kg TMP IV q6-12h

Peds: 5mg/kg TMP IV q6-12h

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CNS Infection Tx Dosing:
Vanco

Adults: 15mg/kg IV q8-12h

Peds: 15mg/kg IV q6h

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CNS Infection Tx Dosing: HIGH DOSES

Need high doses so that the conc of the abx is 10-30x MIC to kill bacteria and to cross the BBB and keep therapeutic levels

[Normal is 2-4xMIC]

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SUMMARY

1. The main goals of treating bacterial meningitis are to eradicate the infection, decrease signs and sxs, and prevent neurologic sequelae
2. Empirical coverage w/an appropraite abx should be started ASAP if clinical suspicion of meningitis exists; the first abx dose should not be withheld if LP is delayed
3. Maximize abx doses to optimize CNS penetration
4. Assess close contacts for appropriate prophylaxis
5. Encephalitis cause by West Nile or HSV require specific therapy to prevent morbidity and mortality