2 - C. Dif Flashcards

1
Q

Describe Toxin A

A

-Major pathogenic factor and has been characterized as an enterotoxin that causes intestinal fluid secretion, mucosal injury, and inflammation through actin disaggregation, intracellular calcium release, and damage to neurons.

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2
Q

Describe Toxin B

A

-Nonenterotoxic cytotoxin that causes depolymerization of filamentous actin and mediates more potent damage to human colonic mucosa than toxin A.

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3
Q

______ = enterotoxin

A

Toxin A

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4
Q

______ = cytotoxin

A

Toxin B

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5
Q

Which toxin is worse?

A

Toxin B

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6
Q

Is C. dif dose dependent?

A

No.

If an AB causes C. diff it needs to be removed, reducing dose of that agent will have no effect

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7
Q

ESBL

A

extended spectrum beta lactamases

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8
Q

Describe the bug of C. dif (characteristics)

A
  • anaerobic
  • GP
  • spore-forming bacilli
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9
Q

C. dif colonizes ___% of hospitalized patients (fecal-oral transmission)

A

20-50

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10
Q

C. dif causes _____% of antimicrobial-associated diarrhea

A

10-20

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11
Q

C. dif causes _____% of antimicrobial-associated colitis

A

50-70

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12
Q

C. dif enterotoxin (A) and cytotoxin (B) cause ??

A

infection, inflammation, and colitis

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13
Q

C. dif has __% infection-related mortality

A

5

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14
Q

NAP1 strain is hyper-virulent strain of C. dif associated with hyper-production and _________-type toxin

A

C. perfringes

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15
Q

NAP1 strain associated with _______, first identified in Quebec where incidence increased from 36-156 cases per 100,000 between 1991 and 2003

A

outbreaks

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16
Q

Current estimates suggest _____% of CDI associated with NAP1

A

30-50

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17
Q

NAP1 is associated with higher rates of ?

A
  • treatment failure
  • 2x recurrence
  • 2x complications
  • 4x attributable mortality compared with non-NAP1
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18
Q

What is the main risk factor for CDI?

A

antimicrobial therapy

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19
Q

CDI

A

C. difficile infection

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20
Q

When does CDI typically result ?

A

within 4-9 days (up to 8 weeks) after AB therapy

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21
Q

Which antibiotics are at high risk of causing CDI?

A
  • Cephalosporins
  • Fluoroquinolones
  • Penicillins

CFP

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22
Q

Which antibiotics are at moderate risk of causing CDI?

A
  • Macrolides
  • Sulfonamides

MS

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23
Q

Which antibiotics are at low risk of causing CDI?

A
  • Aminoglycosides
  • Tetracyclines

AT

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24
Q

List other risk factors for getting CDI (besides being on high-risk antibiotics)

A
  • hospitalization > 72 hours
  • elderly, debilitated, multiple co-morbidities, severe underlying disease, immunocompromised
  • nasogastric tube, gastric acid suppression (antacids, H2 blockers, PPIs)
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25
Q

Why is gastric acid suppression a risk factor for C. dif?

A

PPI’s, antacids, & H2 blockers cause the pH to increase and therefore makes it a better environment for C. dif to grow

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26
Q

What are some clinical signs and symptoms of CDI?

A
  • watery diarrhea with >3 unformed stools in 24 hours

- nausea, abdominal pain, high fever, very high leukocytosis

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27
Q

What are some complications that can arise from C. dif?

A
  • septic shock

- pseudomembranous or fulminant colitis, ileus, toxic megacolon, perforation (may require colon removal)

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28
Q

How is CDI diagnosed?

A
  • positive C. dif toxin in stool of symptomatic patient with diarrhea
  • isolate culture and molecular typing during outbreaks
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29
Q

Does alcohol kill C. diff?

A

No - it is a spore.

30
Q

List some important strategies for preventing CDI

A
  • environmental cleaning and disinfection (C. dif is very infectious)
  • healthcare worker hygiene and hand-washing (alcohol-based sanitizers not effective against spores)
  • single rooms for patients with known CDI, contact/barrier precautions with gloves and gowns for patients with known or suspected CDI
  • antimicrobial stewardship particularly for Clindamycin, FQs, and cephalosporins (high risk for C. dif)
31
Q

Is the use of probiotics warranted for those with C. dif?

A

Data is inconsistent for the primary prevention of antimicrobial-associated diarrhea or CDI

32
Q

Describe the approach for treating CDI

A

a) Discontinue offending antimicrobial, or replace with lower risk agent if needed
b) Supportive measures with hydration
c) avoid anti-motility agents (ex. loperamide, narcotics)
d) Surgery (loop ileostomy, colectomy) for severe, complicated disease
e) antimicrobial therapy for C. dif infection

33
Q

Why do we want to avoid anti-motility agents (loperamide, narcotics) ?

A

need to get toxin out, don’t want to trap it in

34
Q

What is the 1st line agent for mild-moderate CDI?

Include the duration

A

Metronidazole x 10-14 days

35
Q

Why is Metronidazole the 1st line agent for mild-moderate CDI?

A

-preferred based on lower risk of collateral resistance and cost

36
Q

Metronidazole has ____% response rate but lower 80% for NAP1 strains

A

90

37
Q

____ will require a second treatment

A

1 in 5

38
Q

Describe the response with metronidazole

IMPORTANT

A

typically afebrile within 2 days and diarrhea resolution within 5-7 days

39
Q

Adverse effects of Metronidazole (list 4 besides GI)

A
  • metallic taste (9%)
  • disulifiram-reaction
  • CNS (headache 18%, dizziness, confusion)
  • peripheral neuropathy or neurotoxicity (potentially cumulative with multiple courses of therapy)
40
Q

Is metronidazole expensive?

A

approx $20 for 10 day course

41
Q

Besides metronidazole, what else can be used to treat mild-moderate C. diff? Include duration.

A

Vanco x 10-14 days

42
Q

Why can’t you give Vanco IV for C. dif?

A

Bc you want it in the GI tract where the infection is.

43
Q

Who is vancomycin preferred for in C. dif?

A
  • pregnant or nursing women
  • metro-intolerance
  • metro treatment failure
  • severe infection
44
Q

Is Vanco less effective than metronidazole for C. dif?

A

No - at least as effective as Metro

45
Q

What has fewer side effects:

Metro or Vanco

A

Vanco - since it is oral, vancomycin is not absorbed systemically and SE are not bad like metro

46
Q

What is our concern with giving a patient Vanco?

A

collateral resistance, especially VRE

47
Q

Is Vanco expensive?

A

Yes - capsules are $750

48
Q

When is Vanco suggested?

A

If GI symptoms > 5 days, fever > 3 days, worsening or deteriorating during therapy

**If patient is on metro and still having diarrhea on day 5 of therapy, consider this a failure in treatment

49
Q

Vanco or Metro:

What is better against NAP1?

A

Vanco

50
Q

Severe infection associated with who/what?

A
  • elderly, debilitated, inflammatory bowel disease, immunocompromised
  • serum albumin < 30 g/L and WBC > 15, 000 or abdominal tenderness or SCR 1.5 x baseline
51
Q

What would indicate a very severe infection?

A
  • in critically ill with fulminant infection or septic shock

- ACG suggest ICU, hypotension, T > 38.5, ileum, confusion, WBC > 35,000 or <2000, organ failure)

52
Q

Treatment for a very severe CDI?

A

Vanco 500mg + Metro 500mg

I assume x 10-14 days

53
Q

Why is Vanco 500mg q6h instead of Vanco 125mg q6h ?

A

based on expert opinion only, consider 125mg for PO and 500mg for NG or PR

54
Q

What would constitute recurrence?

A

Symptoms and positive C. difficile toxin within 8 weeks of initial episode.

55
Q

___% chance of recurrence rate with multiple recurrences thereafter

A

25

56
Q

For __________:
Consider probiotics such as Saccharomyces boulardii (500mg q12h), Lactobacilli rhamnosus GG, despite weak evidence for the secondary prevention of recurrent CDI

A

recurrence

57
Q

What is the treatment for the 1st recurrence of CDI?

A

repeat initial therapy (50% response rate)

58
Q

What is the treatment for > 2nd recurrence of CDI?

A

Vanco pulsing or tapering recommended in guidelines despite weak evidence
(ex. 125 mg q6h x 14 days, then q12h x 7d, q24h x 7d and q2-3d x 2-8 weeks

59
Q

What is an alternative drug for recurrent CDI?

A

Fidaxomicin

60
Q

What class if Fidaxomicin in?

A

macrocyclic antimicrobial

61
Q

Fidaxomicin is ______ absorbed therefore well tolerated

A

poorly

62
Q

When is Fidaxomicin used?

A

Used as last option for when multiple recurrence occurs

63
Q

Is Fidaxomicin expensive?

A

Yes - $2200 for 10 days

64
Q

FMT can also be done. What is this?

A

Fecal microbiota transplant - from healthy donor to alter and increase gut diversity

65
Q

Describe how FMT is done

A

performed via nasogastric, nasojejunal, gastrostomy tube, colonoscopy or enema following antimicrobial therapy for C. dif infection

66
Q

FMT has >___% response rate

A

80

67
Q

Cons of FMT?

A
  • lacks standardized products and procedures

- used for desperate patients

68
Q

When are probiotics a risk?

A

Only in immunocompromised patients (introducing bacteria into their gut)

69
Q

What are some other investigational options?

A
  • monoclonal Toxin A and B antibodies

- C. difficile vaccine

70
Q

What AB has HIGHEST risk of causing C. dif ?

A

Clindamycin