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PHAR255 > Meningitis > Flashcards

Meningitis Flashcards

1
Q

What is meningitis?

A

inflammation around the membranes that surround the brain and spinal cord
-involves arachnoid, pia mater, CSF
-inflammatory process in the subarachnoid space can extend around the brain, spinal cord and ventricles
-inflammation due to infection, stroke, tumors, trauma, etc

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2
Q

What proportion of people develop some type of neurologic sequelae due to meningitis?

A

1/3 to 1/2

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3
Q

Differentiate bacterial and aseptic meningitis.

A

bacteria:
-acute meningeal inflammation caused by bacterial infection
-usually evokes a PMN response within the CSF
aseptic:
-meningeal inflammation without evidence of bacteria
-there is no readily identifiable organism on routine culture

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4
Q

What can cause aseptic meningitis?

A

could be anything that is not bacterial BUT also includes some bacterial causes not easily grown
could be viral, fungal, syphilis, TB, Lyme, atypical bacteria
could also be chemical irritation, malignancy or drug induced

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5
Q

What are some protective barriers to the brain?

A

the meninges
skull
the blood brain barrier
the blood-CSF barrier
once past these barriers, there is a lack of host defense mechanisms

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6
Q

What are the three ways that meningitis can be acquired?

A

hematogenous: spread from the blood
contiguous: from an URTI
direct inoculation: surgery or trauma

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7
Q

Describe the series of events leading up to bacterial meningitis.

A
  1. mucosal colonization and bacterial invasion of the host and CNS
  2. bacterial replication in the subarachnoid space
  3. inflammation/pathophysiologic changes
  4. increased intracranial pressure, cerebral edema and neuronal damage
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8
Q

What is special about bacteria that commonly cause meningitis?

A

they have properties that can enhance their virulence
-H. influenzae, S. pneumoniae, and N. meningitidis make IgA protease which allows them to colonize nasopharyngeal mucosa by cleaving antibodies
-N.meningitidis can adhere to cells by means of pili
-all 3 are encapsulated by a polysaccharide capsule which inhibits phagocytosis

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9
Q

Does the CSF have strong host defenses?

A

poor host defenses in the CSF
-low complement levels, low antibody levels
-bacteria are able to quickly multiply

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10
Q

What is the result of the inflammatory cascade which occurs to someone with meningitis?

A

cytokines are released = promotes migration of neutrophils into the CSF
neutrophils release PGs, MMPs, etc which cause edema and swelling

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11
Q

What are the risk factors for bacterial meningitis?

A

congenital or traumatic defects
previous viral infection
age (elderly, young children, infants)
low SES
crowding
exposure to pathogens
-recent colonization
-contact with meningitis pts
-IV drug use
-bacterial endocarditis
-immunosuppression
-surgery or trauma
-splenic dysfunction

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12
Q

Describe the CSF.

A

most is produced in ventricles by choroid plexus
flows unidirectionally from ventricles to subarachnoid space then down through spinal cord
-drug admin in lumbar area does not result in sig conc above that point
normally clear with few WBCs; protein < 500mg/ml; glucose conc approx 50-60% of simultaneous peripheral glucose

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13
Q

What are the most common pathogens that cause meningitis?

A

S. pneumonia
N. meningitidis
Group B streptococcus
Listeria monocytogenes

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14
Q

True or false: the causative pathogens of meningitis vary by age

A

true

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15
Q

Which pathogen used to account for ~50% of meningitis cases?

A

H. influenzae
-vaccination has almost completely eliminated
S. pneumoniae now predominates

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16
Q

Which organisms are most likely to cause meningitis in premature infants and neonates ( < 1 month)?

A

E. coli
Strep agalactiae
L. monocytogenes
Klebsiella species

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17
Q

Which organisms are most likely to cause meningitis in infants and kids (1-23 months)?

A

S. pneumoniae
N. meningitidis
(H. influenzae)

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18
Q

Which organisms are most likely to cause meningitis in people aged 2-50 years old?

A

S. pneumoniae
N. meningitidis

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19
Q

Which organisms are most likely to cause meningitis in people older than 50 years old?

A

S. pneumoniae
N. meningitidis
L. monocytogenes
gram negative enterics

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20
Q

Which organisms are most likely to cause meningitis in patients receiving surgery or due to trauma?

A

Staph infection
gram negative bacilli

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21
Q

Which organisms are most likely to cause meningitis in patients with a brain abscess?

A

polymicrobial (aerobic and anaerobic)

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22
Q

What are the components in the diagnosis of meningitis?

A
  1. physical exam
  2. laboratory tests
  3. age of patient (clue to organism)
  4. history of presenting illness
  5. past medical history (IV drug use, asplenic, immunocomp)
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23
Q

What are the signs and symptoms of meningitis?

A

classic triad: fever, headache, neck stiffness
altered mental status
vomiting
seizures
malaise

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24
Q

What percentage of patients experience the classic triad of symptoms?

A

25-50%
-stiff neck only present ~30% of time

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25
Q

Who are some patients that might not have the classic features of meningitis?

A

infants, elderly, immunosuppressed
infants: non-specific
-irritable, lethargy, poor feeding, fever, seizures, rash, breathing changes, bulging fontanelle
elderly: often only confusion or altered mental status

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26
Q

What are some laboratory tests that will be conducted for meningitis?

A

lumbar puncture
CSF gram stain and culture
CSF chemistry
CSF WBC count

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27
Q

What is the use of the lumbar puncture for meningitis?

A

obtain fluid for cell counts
for gram stain and C & S

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28
Q

When must we be careful with a lumbar puncture?

A

elevated intracranial pressure

29
Q

What should be done while waiting to identify the infecting pathogen of meningitis?

A

medical emergency
-start empiric antibiotics within 1hr of diagnosis

30
Q

What is the expected CSF chemistry of someone with bacterial meningitis?

A

low glucose
elevated protein

31
Q

What are the expected CSF WBC counts in someone with bacterial meningitis?

A

normally < 5 x 10 to the 6/L; most monocytes
will often be > 500 x 10 to the 6/L; mostly PMNs

32
Q

What are some acute complications of bacterial meningitis?

A

shock
resp failure
abscess
seizures
altered mental status
apnea
increased intracranial pressure
death

33
Q

What are some sequelae of bacterial meningitis?

A

seizure disorder
impaired cognition/intellect
personality changes
gait disturbances
dizziness
focal neurologic deficit (blindness, paralysis, paresis)

34
Q

What are the mortality rates of bacterial meningitis?

A

4-10% in children
25% in adults
50% in elderly

35
Q

What increases the risk of mortality from bacterial meningitis?

A

decreased consciousness at admission
signs of increased ICP
seizures within 24h of admission
infants and older than 50yrs
delay in treatment
need for mechanical ventilation

36
Q

What are some treatment considerations for bacterial meningitis?

A
  1. adequate concentration of antibiotic in the CSF
  2. activity of antibiotic in CSF
  3. direct (focal) antibiotic administration
37
Q

Why cant all drugs cross the BBB?

A

BBB consists of tightly joined capillary endothelial tissue which prevents drug passage
drug must go through endothelial cells rather than between them

38
Q

What happens to BBB efflux pumps with inflammation?

A

inhibited
may also be blocked with probenicid

39
Q

What determines concentration of antibiotic in the CSF?

A

lipid solubility
plasma protein binding
molecular weight
ionization

40
Q

What happens to antibiotic penetration with inflammation?

A

penetration increases
careful not to decrease dose as patient gets better
-penetration will decrease

41
Q

Which antimicrobials can achieve therapeutic levels in CSF without inflammation?

A

acyclovir
chloramphenicol
FQs
fluconazole
linezolid
metronidazole
sulfonamides, trimethoprim
pyrazinamide, rifampin, isoniazid

42
Q

Which antibiotics can achieve therapeutic levels in CSF with meningeal inflammation?

A

ampicillin, pen G, piperacillin
aztreonam
cefotaxime, ceftriaxone, cefepime, ceftazidime, cefuroxime
imipenem, meropenem
vancomycin

43
Q

Which antibiotics show nontherapeutic levels in CSF with or without inflammation?

A

aminoglycosides
1st gen cephalosporins
2nd gen cephalosporins
doxycycline
intraconazole
amphotericin B
beta-lactamase inhibitors

44
Q

What kind of antibiotics are needed for bacterial meningitis?

A

bactericidal agents

45
Q

What are the routes of administration for bacterial meningitis?

A

intralumbar
intracisternal
intraventricular

46
Q

What are some considerations with antibiotic administration for bacterial meningitis?

A

drug may cause chemical meningitis
-use preservative free
may introduce nosocomial infection
less volume the better

47
Q

What are some general considerations for treatment of bacterial meningitis?

A

start antibiotics immediately
empiric therapy based on age, hx, underlying dx, gram stain
generally IV admin
give full doses for entire course of therapy
rpt lumbar puncture in 1-2d to ensure CSF sterilization
-may not be done if common pathogen and pt response

48
Q

When is treatment of bacterial meningitis extended?

A

subdural abscess
prolonged fever
delayed sterilization of CSF
persistent symptoms and signs

49
Q

What is the duration of therapy of bacterial meningitis if the patient is responding well ?

A

S. pneumoniae: 14 days
N. meningitidis: 5-7 days
H. influenzae: 7-14 days
Group B strep: 14-21 days
gram negative bacilli: 21 days
abscess: 4-6 weeks

50
Q

List the empiric antibiotic therapy of choice for bacterial meningitis for the following groups:
- < 1 month old
- 1 month - 50 years old
- > 50 years old
- trauma or neurosurgery

A

< 1 month: ampicillin + cefotaxime or AMG
1 mo-50yrs: vancomycin + 3rd gen ceph (ceftriaxone or cefotaxime)
> 50yrs: vancomycin + ampicillin + 3rd gen ceph
trauma or surgery: vancomycin + cefepime/ceftazidime/meropenem

51
Q

What is the therapy for bacterial meningitis if caused by S. pneumoniae?

A

vancomycin + 3rd gen ceph
pen G or ampicillin if pen susceptible
alt: FQ, meropenem

52
Q

What is the therapy for bacterial meningitis if caused by N. meningitidis?

A

3rd gen ceph, ampicillin, pen G
alt: FQ, ampicillin

53
Q

What is the therapy for bacterial meningitis if caused by L. monocytogenes?

A

ampicillin or pen G +/- AMG
alt: TMP/SMX, meropenem

54
Q

What is the therapy for bacterial meningitis if caused by strep agalactiae?

A

ampicillin or pen G
alt: 3rd gen ceph

55
Q

What is the therapy for bacterial meningitis if caused by H. influenzae?

A

3rd gen ceph
alt: cefepime, meropenem, FQ

56
Q

What is the therapy for bacterial meningitis if caused by E. coli?

A

3rd gen ceph
cefepime, meropenem, FQ, TMP/SMX

57
Q

How should AMGs be given for bacterial meningitis?

A

directly into CSF (except neonates) due to poor penetration
synergistic with penicillins in IV form

58
Q

Which cephalosporins can penetrate the CSF?

A

1st gen: inadequate CNS penetration
2nd gen: penetrate but delayed sterilization, failure, resistance
3rd gen: standard empiric therapy for meningitis and DOC for gram negative bacilli

59
Q

What are some supportive therapies to prevent/treat edema, hydrocephalus and inflammation?

A

mannitol: osmotic diuretic that can decrease ICP
shunts: drain excess fluid from brain
steroids

60
Q

What is an example of a corticosteroid regimen for meningitis?

A

dexamethasone 0.15mg/kg q6h for 2-4d

61
Q

Why is corticosteroid use in meningitis controversial?

A

decreasing inflammation will decrease antibiotic penetration BUT killing organisms results in release of inflammatory mediators

62
Q

When should corticosteroids be discontinued in bacterial meningitis?

A

d/c within 48h if S. pneumoniae or H. influenzae not cultured

63
Q

How should corticosteroids be administered in bacterial meningitis?

A

before or within 2h of antimicrobials

64
Q

What are the benefits of corticosteroids in bacterial meningitis?

A

can decrease hearing loss in kids (esp if H. influenzae)
sig decrease in mortality and reduced hearing loss in adults

65
Q

When are corticosteroids recommended for bacterial meningitis?

A

> 6 weeks old and H. influenzae infection
consider if > 6 weeks old and pneumococcal infection

66
Q

Describe appropriate monitoring parameters for bacterial meningitis.

A

check C & S results
lab: CBC
rpt lumbar puncture
signs and symptoms q4h
antibiotic AE
complications

67
Q

Who should receive prophylaxis for meningitis?

A

high risk contacts: start ASAP
-household or close contacts
-intimate non-household contacts
-direct exposure to secretions
-school/daycare
HCP do not need unless contact with secretions

68
Q

What are the options for prophylaxis of meningitis?

A

meningococcal:
-rifampin
-alt: ciprofloxacin, ceftriaxone
H. influenzae: rifampin
not given if pneumococcal

PHAR255 (24 decks)

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