Lecture 3/4- Journal Club for C. Diff Flashcards
Describe C. Diff
- Gram positive
- Spore forming Bacillus
What are the two toxins produced by C. Diff and what do they destory
Toxin A - enterotoxin - tight cell junctions
Toxin B - cytotoxin - cytoskeletons
Which toxin is essenctial for C. Diff virulence
Toxin B
What made this a phase 3 trial?
- Clinical setting
- Length
- Compared treatment
- Randomized
MODIFY I vs MODIFY II
MODIFY II took out Actozumab alone because it was killing people
What was the standard of care for the trial?
Metroniadozole (no longer accepted)
Passive immunity vs. Active immunity
Passive - produced in an animal and injected in humans
Active - acquired on our own
What was the inclusion criteria for the C. Diff study?
- Over 18
- Met C diff definition
- Receiving standard oral of care antibiotics
What was the exclusion criteria for the C. Diff study?
- Chronic diarrheal illness (confounding)
- Surgery for CDI planned in 24 hours
- Treatment with IVIG in previous 6 months
Why is chronic diarrheal illness an exclusion criteria for the C. Diff experiment?
Confounding variable because …..
Primary endpoint for C. Diff trail?
Proportion of participants with recurrent C. Diff infection during 12 week follow up
What was more effective bezlotoxumab or bezlotoxumab+actoxumab?
Bezlotoxumab
Secondary Outcome
More efficent in these groups:
- Recurrent CDI in patients over 65
- Recurrent in CDI in immunocompromised patients
- Recurrent CDI in patients with severe CDI
Describe gram positive bacteria
- Thick cell wall
- Lots of cross linking
- Purple stain
Describe gram negative bacteria
- Thin peptidoglycan layer
- Periplasmic space
- Stains red
Some gram ____ can form spores as a survival mechanism
positive
What do spores contain?
- Complete copy of chromosomes
- Bare minimum concentration of essential proteins and ribosomes
- High concentration of calcium
What acid binds calcium and stabilizes the contents of C.diff
Dipicolinic Acid
What is the procress to stain bacteria?
- Crystal violet
- Decolorizer
- Safranin
How is gram stain useful?
First data we get it tells us what we are dealign with a little and we can guess which antibiotics to use
Gram positive stain
Purple (crystal violet)
Gram negative stain
Red (Safarin)
Gram negative has what three things postives don’t have?
- Outer membrane
- Lipopolysaccharide
- Endotoxin
Which is more susceptible to penicillin?
Gram positive
What are the risk factors for C. Diff?
- Antibiotic Use
- Age
- Gastric Acid Suppression
- Gastrointestinal surgery
- Long length of stay in hospital
- Serious illness
Which antibiotics are associated with C. Diff risk?
- Fluoroquninolone (Cipro, Levofloxacin)
- Clindamycin
How do PPIs increase risk for C. Diff?
Proton pump inhibitors causes changes in the pH
Allow bacteria to grow
What are some examples of PPIs
Protonix
Nexium
Pathophysiology of C. diff
- Colonocyte death
- Loss of intestinal barrier function
- Neutrophilic colitis
C. Diff disease presentation
- Watery diarrhea
- Lower abdominal pain and cramping
- Low grade fever
- Nausea
- Anorexia
- Leukocytosis (elevated white blood cell count)
Diseases caused by C. Diff
5
- Pseudomembranous colitis (PMC)
- Toxic megacolon
- Perforations of the colon
- Sepsis
- Death (rarely)
C. Diff diagnosis
- Toxins detection in feces
T/F
Labs distinguish between active infection and carrier infection for C. Diff
F
Stools may remain positive after clinical recovery so there is no role for repeated testing for cure
C. Diff treatment
- Stop inciting antibiotics
- Place in isolation
- Oral vancomycin or Fidaxomicin
- Fecal transplant
Prevention and control for C. Diff
- Single patient room
- Disposable equipment
- Hand washing
Describe an example of infection control policy
- Putting a patient with C. diff in isolation
last slides of the ppt
Describe the phases of a clinical trial
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
Monoclonal antibodies can have _______, in that they bind to the same epitope
monovalent affinity
How are monoclonal antibodies produced?
1, Mouse given antigen
- Spleen cells are taken and combinded with Myeloma cells
- Hybridomas are the result
- Culture in media to select positive cells
- Harvest monoclonal antibodeis
Bezlotoxumab is a human monoclonal antibody that binds to which toxin
IgG1; toxin B
does not work on toxin A
Actotoxumab is a human monoclonal antibody that binds to which toxin
Toxin A
