Lecture 3/4- Journal Club for C. Diff

Question 1

Describe C. Diff

Answer 1

• Gram positive

- Spore forming Bacillus

Question 2

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

Answer 2

Toxin A - enterotoxin - tight cell junctions

Toxin B - cytotoxin - cytoskeletons

Question 3

Which toxin is essenctial for C. Diff virulence

Answer 3

Toxin B

Question 4

What made this a phase 3 trial?

Answer 4

1. Clinical setting
2. Length
3. Compared treatment
4. Randomized

Question 5

MODIFY I vs MODIFY II

Answer 5

MODIFY II took out Actozumab alone because it was killing people

Question 6

What was the standard of care for the trial?

Answer 6

Metroniadozole (no longer accepted)

Question 7

Passive immunity vs. Active immunity

Answer 7

Passive - produced in an animal and injected in humans

Active - acquired on our own

Question 8

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

Answer 8

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

Question 9

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

Answer 9

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

Question 10

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

Answer 10

Confounding variable because …..

Question 11

Primary endpoint for C. Diff trail?

Answer 11

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

Question 12

What was more effective bezlotoxumab or bezlotoxumab+actoxumab?

Answer 12

Bezlotoxumab

Question 13

Secondary Outcome

Answer 13

More efficent in these groups:

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

Question 14

Describe gram positive bacteria

Answer 14

• Thick cell wall
• Lots of cross linking
• Purple stain

Question 15

Describe gram negative bacteria

Answer 15

• Thin peptidoglycan layer
• Periplasmic space
• Stains red

Question 16

Some gram ____ can form spores as a survival mechanism

Answer 16

positive

Question 17

What do spores contain?

Answer 17

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

Question 18

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

Answer 18

Dipicolinic Acid

Question 19

What is the procress to stain bacteria?

Answer 19

1. Crystal violet
2. Decolorizer
3. Safranin

Question 20

How is gram stain useful?

Answer 20

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

Question 21

Gram positive stain

Answer 21

Purple (crystal violet)

Question 22

Gram negative stain

Answer 22

Red (Safarin)

Question 23

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

Answer 23

• Outer membrane
• Lipopolysaccharide
• Endotoxin

Question 24

Which is more susceptible to penicillin?

Answer 24

Gram positive

Question 25

What are the risk factors for C. Diff?

Answer 25

- Antibiotic Use - Age - Gastric Acid Suppression - Gastrointestinal surgery - Long length of stay in hospital - Serious illness

Question 26

Which antibiotics are associated with C. Diff risk?

Answer 26

- Fluoroquninolone (Cipro, Levofloxacin) | - Clindamycin

Question 27

How do PPIs increase risk for C. Diff?

Answer 27

Proton pump inhibitors causes changes in the pH | Allow bacteria to grow

Question 28

What are some examples of PPIs

Answer 28

Protonix | Nexium

Question 29

Pathophysiology of C. diff

Answer 29

- Colonocyte death - Loss of intestinal barrier function - Neutrophilic colitis

Question 30

C. Diff disease presentation

Answer 30

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

Question 31

Diseases caused by C. Diff | 5

Answer 31

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

Question 32

C. Diff diagnosis

Answer 32

- Toxins detection in feces

Question 33

T/F Labs distinguish between active infection and carrier infection for C. Diff

Answer 33

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

Question 34

C. Diff treatment

Answer 34

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

Question 35

Prevention and control for C. Diff

Answer 35

- Single patient room - Disposable equipment - Hand washing

Question 36

Describe an example of infection control policy

Answer 36

- Putting a patient with C. diff in isolation | last slides of the ppt

Question 37

Describe the phases of a clinical trial

Answer 37

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

Question 38

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

Answer 38

monovalent affinity

Question 39

How are monoclonal antibodies produced?

Answer 39

1, Mouse given antigen 2. Spleen cells are taken and combinded with Myeloma cells 3. Hybridomas are the result 4. Culture in media to select positive cells 5. Harvest monoclonal antibodeis

Question 40

Bezlotoxumab is a human monoclonal antibody that binds to which toxin

Answer 40

IgG1; toxin B | does not work on toxin A

Question 41

Actotoxumab is a human monoclonal antibody that binds to which toxin

Answer 41

Toxin A