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Pharm > Meningitis and Encephalitis > Flashcards

Meningitis and Encephalitis Flashcards

1
Q

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

A

Meningitis

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2
Q

Acute inflammation/infection of brain parenchyma

A

Encephalitis

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3
Q

Gram + cocci

A

Streptococcus pneumonia

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4
Q

Gram - coccobacilli

A

Haemophilus influenzae

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5
Q

Gram - cocci

A

Neisseria meningitidis

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6
Q

Gram - bacilli

A

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

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7
Q

Gram + bacilli

A

Listeria monocytogenes

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8
Q

Risk factors for Meningitis

A 
Sickle cell anemia
Asplenic status
Cochlear implants
Head trauma
Immunosuppression
Mastoiditis, URT infection, Otitis media 
Exposure to cigarette smoke
Alcoholism
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9
Q

Incidence trend

A

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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10
Q

Vaccines

A

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

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11
Q

Sequelae

A 
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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12
Q

Adheres to the skull

A

Dura mater

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13
Q

Lies between the dural and pia maters

A

Arachnoid mater

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14
Q

Lies directly over brain tissue

A

Pia mater

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15
Q

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

A

Subarachnoid space

-CSF flows thru this space

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16
Q

CSF flows thru this space

A

Subarachnoid space

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17
Q

Where and how is CSF produced

A

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

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18
Q

CSF flow

A

Unidirectionally, down the spinal cord

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19
Q

CSF Amounts

A

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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20
Q

Injecting drugs into the CSF cavity

A

Intrathecal

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21
Q

Injecting drugs into ventricles

A

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

MC for neurosurgery or shunt infections

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22
Q

Factors that INCREASE penetration of abx into the CSF

A 
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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23
Q

Medications with therapeutic levels in CSF +/- Inflammatoin

A

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

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24
Q

Medications with therapeutic levels WITH inflammed meninges

A 
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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25
Q

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

A 
Aminoglycosides
First generation cephalosporins
Second generation cephalosporins (Except cefuroxime)
Clindamycin
Amphotericin - Antifungal
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26
Q

Pathophysiology of Bacterial Meningitis

Sources of Infection

A

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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27
Q

CNS response to infection

A

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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28
Q

Signs/Sxs of Meningitis

A

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

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29
Q

Diagnostic tests for meningitis

A

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

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30
Q

CSF Findings

A

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

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31
Q

Likely Meningitiis Pathogens in Age <1 month

A

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

32
Q

Likely Meningitis Pathogens in Age 1-23 months

A

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

33
Q

Likely Meningitis Pathogens in Age 2-50 yrs

A

N. menigitidis, S. penumoniae

34
Q

Likely Meningitis Pathogens in Age >50 yrs

A

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

35
Q

Treatment Goals

A

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

36
Q

See Management Algorithm for Adults w/Suspected Bacterial meningitis

A

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)

37
Q

NEGATIVE CSF Gram Stain or Gram Stain NOT Available:

Age <1mo Common Pathogens

A

Group B Streptococcus
E. coli
L monocytogenes
Klebsiella sp

38
Q

NEGATIVE CSF Gram Stain or Gram Stain NOT Available:

Age <1mo Antimicrobial Therapy

A

Ampicillin + Cefotaxime
OR
Ampicillin + Aminoglycoside (synnergistic effect)

39
Q

NEGATIVE CSF Gram Stain or Gram Stain NOT Available:

Age 1-23 mo Common Pathogens

A 
S. pneumo
N menigitidis
Group B strep
H flu
E coli
40
Q

NEGATIVE CSF Gram Stain or Gram Stain NOT Available:

Age 1-23 mo Antimicrobial Therapy

A

Vancomycin + 3rd Gen Cephalosporin (Cefotaxime or Ceftriaxone)

41
Q

NEGATIVE CSF Gram Stain or Gram Stain NOT Available:

Age 2-50 yrs Common Pathogens

A

N menigitidis

S penumoniae

42
Q

NEGATIVE CSF Gram Stain or Gram Stain NOT Available:

Age 2-50 yrs Antimicrobial Therapy

A

Vancomycin + 3rd Gen Cephalosporin (Cefotaxime or Ceftriaxone)

43
Q

NEGATIVE CSF Gram Stain or Gram Stain NOT Available:

Age >50 yrs Common Pathogens

A

S pneumoniae
N meningitidis
L monocytogenes
Gram - bacilli

44
Q

NEGATIVE CSF Gram Stain or Gram Stain NOT Available:

Age >50 yrs Antimicrobial Therapy

A

Vancomycin + Ampicillin + 3rd Gen Cephalosporin

45
Q

POSITIVE CSF Gram Stain

Gram + Diplococci

A

S. pneumoniae

Ceftriaxone or Cefotaxime + Vanco + Dexamethasone

46
Q

POSITIVE CSF Gram Stain

Gram - Diplococci

A

N meningitidis

Ceftriaxone or Cefotaxime

47
Q

POSITIVE CSF Gram Stain

G + Bacilli

A

L monocytogenes

Ampicillin +/- Gentamycin

48
Q

POSITIVE CSF Gram Stain

Gram - Bacilli

A

H flu, Coliforms, Pseudomonas aeruginosa

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

49
Q

PATHOGEN IDENTIFICATION & SENSITIVITY KNOWN

Group B Strep (Gram + cocci)

A

Penicillin G or Ampicillin

Alt: Ceftriaxone or Cefotaxime

14-21 Days

50
Q

PATHOGEN IDENTIFICATION & SENSITIVITY KNOWN

H flu (Gram - bacilli)

A

Ceftriaxone

Alt: Chloramphenicol, Cipro, Aztreonam

7 Days

51
Q

PATHOGEN IDENTIFICATION & SENSITIVITY KNOWN

N meningitidis (Gram - diplococci)

A

Ceftraixone

Alt: Chloramphenicol

7 Days

52
Q

PATHOGEN IDENTIFICATION & SENSITIVITY KNOWN

L monocytogenes (Gram + bacilli)

A

Ampicillin +/- Gentamicin

Alt: TMP/SMX, Meropenem

> 21 Days

53
Q

PATHOGEN IDENTIFICATION & SENSITIVITY KNOWN

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

A

Penicillin G or Ampicillin

Alt: Ceftriaxone or Chloramphenicol

10-14 Days

54
Q

PATHOGEN IDENTIFICATION & SENSITIVITY KNOWN

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

A

Ceftriaxone or Cefotaxime

Alt: Cefepime or Meropenem

10-14 Days

55
Q

PATHOGEN IDENTIFICATION & SENSITIVITY KNOWN

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

A

Vanco + Ceftriaxone (Or Cefotaxime)

Alt: Moxifloxacin

10-14 Days

56
Q

PATHOGEN IDENTIFICATION & SENSITIVITY KNOWN

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

A

Vanco + Ceftriaxone (Or Cefotaxime)

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

10-14 Days

57
Q

Dexamethasone Rationale

A

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

58
Q

Adjunctive Dexamethasone in Bacterial Meningitis

A

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

59
Q

Who should receive meningitis prophylaxis?

A

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

60
Q

H. flu prophylaxis

A

Rifampin 600mg PO q24h x 4days

61
Q

Neisseria meningitidis prophylaxis

A

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

62
Q

Viral Encephalitis Etiology

A 
Enteroviruses (85%) - MC
Arboviruses (St. Louis, La Crosse, West Nile)
Adenoviruses
HSV
HIV
Influenza
Cytomegalovirus
63
Q

Viral Encephalitis Clinical Presentation

A 
HA
Mild fever
Nuchal rigidity +/-
Malaise
Photophobia
Decreased LOC
Rash (West Nile)
Nausea
Vomiting
64
Q

Viral Encephalitis Clinical Course

A

Most are self limiting (1-2 wks duration)

West Nile and HSV associated with significant morbidity and mortality

65
Q

Viral Encephalitis Treatment: Enteroviral

A

Supportive care: Fluids, antipyretics, analgesics

66
Q

Viral Encephalities Tx: West Nile

A

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

67
Q

Viral Encephalitis Tx: HSV

A

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

68
Q

CNS Infection Tx Dosing:

Acyclovir

A

Adult: 10mg/kg IV q8h

Peds: 20mg/kg IV q8h

69
Q

CNS Infection Tx Dosing:

Ampicillin

A

Adult: 2gm IV q4h

Peds: 75mg/kg IV q6h

70
Q

CNS Infection Tx Dosing:

Cefotaxime

A

Adults: 2gm IV q4-6h

Peds: 75mg/kg IV q6-8h

71
Q

CNS Infection Tx Dosing:

Ceftriaxone

A

Adults: 2gm IV q12-24h

Peds: 100mg/kg IV q24h

72
Q

CNS Infection Tx Dosing:

Penicillin G

A

Adults: 4MU IVq4h

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

73
Q

CNS Infection Tx Dosing:

SMX/TMP

A

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

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

74
Q

CNS Infection Tx Dosing:

Vanco

A

Adults: 15mg/kg IV q8-12h

Peds: 15mg/kg IV q6h

75
Q

CNS Infection Tx Dosing: HIGH DOSES

A

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]

76
Q

SUMMARY

A
  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

Pharm (9 decks)

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