Lecture 3/4- Journal Club for C. Diff Flashcards

1
Q

Describe C. Diff

A
  • Gram positive

- Spore forming Bacillus

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2
Q

What are the two toxins produced by C. Diff and what do they destory

A

Toxin A - enterotoxin - tight cell junctions

Toxin B - cytotoxin - cytoskeletons

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3
Q

Which toxin is essenctial for C. Diff virulence

A

Toxin B

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4
Q

What made this a phase 3 trial?

A
  1. Clinical setting
  2. Length
  3. Compared treatment
  4. Randomized
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5
Q

MODIFY I vs MODIFY II

A

MODIFY II took out Actozumab alone because it was killing people

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6
Q

What was the standard of care for the trial?

A

Metroniadozole (no longer accepted)

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7
Q

Passive immunity vs. Active immunity

A

Passive - produced in an animal and injected in humans

Active - acquired on our own

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8
Q

What was the inclusion criteria for the C. Diff study?

A
  • Over 18
  • Met C diff definition
  • Receiving standard oral of care antibiotics
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9
Q

What was the exclusion criteria for the C. Diff study?

A
  • Chronic diarrheal illness (confounding)
  • Surgery for CDI planned in 24 hours
  • Treatment with IVIG in previous 6 months
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10
Q

Why is chronic diarrheal illness an exclusion criteria for the C. Diff experiment?

A

Confounding variable because …..

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11
Q

Primary endpoint for C. Diff trail?

A

Proportion of participants with recurrent C. Diff infection during 12 week follow up

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12
Q

What was more effective bezlotoxumab or bezlotoxumab+actoxumab?

A

Bezlotoxumab

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13
Q

Secondary Outcome

A

More efficent in these groups:

  • Recurrent CDI in patients over 65
  • Recurrent in CDI in immunocompromised patients
  • Recurrent CDI in patients with severe CDI
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14
Q

Describe gram positive bacteria

A
  • Thick cell wall
  • Lots of cross linking
  • Purple stain
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15
Q

Describe gram negative bacteria

A
  • Thin peptidoglycan layer
  • Periplasmic space
  • Stains red
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16
Q

Some gram ____ can form spores as a survival mechanism

A

positive

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17
Q

What do spores contain?

A
  • Complete copy of chromosomes
  • Bare minimum concentration of essential proteins and ribosomes
  • High concentration of calcium
18
Q

What acid binds calcium and stabilizes the contents of C.diff

A

Dipicolinic Acid

19
Q

What is the procress to stain bacteria?

A
  1. Crystal violet
  2. Decolorizer
  3. Safranin
20
Q

How is gram stain useful?

A

First data we get it tells us what we are dealign with a little and we can guess which antibiotics to use

21
Q

Gram positive stain

A

Purple (crystal violet)

22
Q

Gram negative stain

A

Red (Safarin)

23
Q

Gram negative has what three things postives don’t have?

A
  • Outer membrane
  • Lipopolysaccharide
  • Endotoxin
24
Q

Which is more susceptible to penicillin?

A

Gram positive

25
Q

What are the risk factors for C. Diff?

A
  • Antibiotic Use
  • Age
  • Gastric Acid Suppression
  • Gastrointestinal surgery
  • Long length of stay in hospital
  • Serious illness
26
Q

Which antibiotics are associated with C. Diff risk?

A
  • Fluoroquninolone (Cipro, Levofloxacin)

- Clindamycin

27
Q

How do PPIs increase risk for C. Diff?

A

Proton pump inhibitors causes changes in the pH

Allow bacteria to grow

28
Q

What are some examples of PPIs

A

Protonix

Nexium

29
Q

Pathophysiology of C. diff

A
  • Colonocyte death
  • Loss of intestinal barrier function
  • Neutrophilic colitis
30
Q

C. Diff disease presentation

A
  • Watery diarrhea
  • Lower abdominal pain and cramping
  • Low grade fever
  • Nausea
  • Anorexia
  • Leukocytosis (elevated white blood cell count)
31
Q

Diseases caused by C. Diff

5

A
  1. Pseudomembranous colitis (PMC)
  2. Toxic megacolon
  3. Perforations of the colon
  4. Sepsis
  5. Death (rarely)
32
Q

C. Diff diagnosis

A
  • Toxins detection in feces
33
Q

T/F

Labs distinguish between active infection and carrier infection for C. Diff

A

F

Stools may remain positive after clinical recovery so there is no role for repeated testing for cure

34
Q

C. Diff treatment

A
  1. Stop inciting antibiotics
  2. Place in isolation
  3. Oral vancomycin or Fidaxomicin
  4. Fecal transplant
35
Q

Prevention and control for C. Diff

A
  • Single patient room
  • Disposable equipment
  • Hand washing
36
Q

Describe an example of infection control policy

A
  • Putting a patient with C. diff in isolation

last slides of the ppt

37
Q

Describe the phases of a clinical trial

A

Phase 1 - Assess drug safety and find dosage

Phase 2 - Efficacy and side effects

Phase 3 - Compare new treatments with current treatment

Phase 4 - Safety and efficacy

38
Q

Monoclonal antibodies can have _______, in that they bind to the same epitope

A

monovalent affinity

39
Q

How are monoclonal antibodies produced?

A

1, Mouse given antigen

  1. Spleen cells are taken and combinded with Myeloma cells
  2. Hybridomas are the result
  3. Culture in media to select positive cells
  4. Harvest monoclonal antibodeis
40
Q

Bezlotoxumab is a human monoclonal antibody that binds to which toxin

A

IgG1; toxin B

does not work on toxin A

41
Q

Actotoxumab is a human monoclonal antibody that binds to which toxin

A

Toxin A