PHAR 255 - C. Diff

Question 1

What is Clostridioides Difficile?

Answer 1

Gram-positive, spore forming, anaerobic bacteria that produces toxins A and B which attack the epithelial cells lining the colon → inflammation → tissue damage to intestinal lining → diarrhea

Question 2

Definition of C. diff Associated Diarrhea

Answer 2

Diarrhea ≥ 3 loose stools per day for 24hrs and positive C. diff toxin
OR
Ileus/pseudomembranous on sigmoid/colonoscopy
OR
Histological/pathological diagnosis of pseudomembranous colitis

Question 3

Pathogenisis:

Endogenous Causes

Answer 3

Bowel flora is disrupted through antimicrobial agents eradicating the normal gut flora AND
Virulent factors produced by C. difficile OR C. difficile toxins A and B are released

Question 4

Pathogenisis:

Exogenous Causes

Answer 4

Infected through fecal-oral route: touching a contaminated surface then the mouth

Question 5

How Can C. Diff be Transmitted?

Answer 5

Carrier in Stool → healthy people can be asymptomatic and infectious (infants < 2yo and neonates are often carriers)
Transmission Through → fecal-oral route when a person touches the contaminated surface with feces then the mouth

Question 6

Presentation of C. Diff

Answer 6

• Watery stool
• Abdominal pain
• Fever
• Leukocytosis (Increased WBC)
• Loss of appetite

Question 7

How is C. Diff Diagnosed?

Answer 7

Symptoms + Toxins
- Take a stool sample in order to test for toxins and genes
- Colonoscopy or sigmoidoscopy can be done to look for pseudomembranes (yellow plaques on colon lining)

Question 8

What Increases Your Risk Of C. Diff?

Answer 8

• Longer hospital stays
• Longer duration of antibiotics
• Exposure to different antibiotics

Question 9

All Antibiotics have the risk of causing CDI and the risk remains for 3 months after antibiotic exposure… Which Antibiotics have a High risk and Low risk of causing CDI?

Answer 9

The broader the antibiotic the more likely it will cause CDI

Low Risk
- Penicillin, aminopenicillin
- Sulfamethoxazole/trimethoprim, macrolides, tetracyclines

High Risk
- Clindamycin
- Fluoroquinolones
- 3rd/4th cephalosporins > 2nd
- Carbapenems
- Beta-lactamase inhibitors (Clav, tazo)

Question 10

Goals of Therapy

Answer 10

• Eradicate C. diff infection within 6 weeks
• Resolution of CDI signs and symptoms by the end of treatment ( day 10 or 14)
• Prevent recurring CDI and other complications, and protect intestinal microbiota while on antibiotics for other infections - ongoing
• Prevent CDI medication adverse reactions - ongoing

Question 11

5 Considerations When Managing C. Diff

Answer 11

1. Stop current antibiotic therapy and/or choose narrowest spectrum antibiotic if possible
2. Replace fluids and electrolytes
3. Avoid anti-motility agents such as loperamide and laxatives
4. Treat the CDI with antibiotics
5. Deprescribe PPIs when possible

Question 12

CDI Categories:

Mild to Moderate

Answer 12

WBC < 15x10^9/L AND Scr ≤ 1.5x baseline

Question 13

CDI Categories:

Severe, Uncomplicated

Answer 13

WBC > 15x10^9/L AND Scr > 1.5x baseline

Question 14

CDI Categories:

Severe, Complicated

Answer 14

Hypotension or shock, ileus, megacolon (abnormal nonobstructive dilation of colon)

Question 15

Drug Therapy:

Initial Episode: Mild-Moderate CDI

Answer 15

1st Line → Vancomycin 125mg po QID for 10-14d
2nd Line → Fidaxomicin 200mg po BID for 10d
3rd Line → Metronidazole 500mg po TID for 10-14d

DON’T NEED TO KNOW DOSES

Question 16

Drug Therapy:

Why is Oral Vancomycin Used?

Answer 16

Oral Vancomycin is ONLY used for CDI
- Systemic absorption is negligible (<10%)
- Concentrates at the site of the CDI (colon)

Vancomycin acts locally in the colon NOT systemically

Question 17

Drug Therapy:

Severe, Uncomplicated CDI

Answer 17

1st Line → Vancomycin 125mg po QID for 10-14d
2nd Line → Fidaxomicin 200mg po BID for 10d
3rd Line → Metronidazole 500mg po TID for 10-14d

DON’T NEED TO KNOW DOSES

Question 18

Drug Therapy:

First Line for Severe, complicated CDI

Answer 18

Vancomycin 125-500mg po/nasogastric tube QID + metronidazole 500mg IV Q8h for 10-14d

Question 19

Drug Therapy:

Recurring Episodes: First Mild-Moderate CDI

Answer 19

1st Line → Vancomycin 125mg po QID for 14d
OR → Fidaxomicin 200mg po BID for 10d
Last Line → Metronidazole 500mg po TID for 10-14d

Peripheral Neuropathy occurs with long and repeated metronidazole exposure so always use as last line trtmt.

Question 20

Drug Therapy:

Recurring Episodes: First Severe, Uncomplicated CDI

Answer 20

1st Line → Vancomycin 125mg po QID for 14d
2nd Line → Fidaxomicin 200mg po BID for 10d

Question 21

Drug Therapy:

Recurring Episodes: Second or Subsequent

Answer 21

• Vancomycin as a prolonged tapered/pulsed regimen → May Consider Fecal microbiota transplant (FMT) following a vancomycin taper
• Monoclonal antibody that binds toxin (toxin A = actoxumab OR toxin B = bezlotoxumab)
• Surgery - usually partial removal of the colon (subtotal colectomy)

Question 22

What is a Fecal Microbiota Transplant (FMT)?

Answer 22

Patients with recurring CDI lack diverse microbiota to resist colonization and replication of C. diff
- Transfers healthy microbiota to patients in the form of stool via nasoduodenal, nasojejunal, oral (capsules), or rectally (enema or colonoscopy)
- Not established as a standard of treatment in Canada

Question 23

In Pediatrics, Why is Routine Testing Discouraged?

Answer 23

Due to high colonization rates

Question 24

Pediatric Drug Therapy:

Initial Episode: Mild-Moderate

Answer 24

1st Line → Metronidazole QID for 10d
2nd Line → Vancomycin QID for 10d

Question 25

# **Pediatric** Drug Therapy: **Initial Episode:** Severe, Uncomplicated

Answer 25

Vancomycin QID for 10d

Question 26

# **Pediatric** Drug Therapy: **Initial Episode:** Severe, Complicated

Answer 26

Vancomycin QID for 10-14d *Consider adding metronidazole QID for 10d*

Question 27

# **Pediatric** Drug Therapy: Recurrence

Answer 27

**Mild-Moderate** → Repeat metronidazole QID for 10d OR vancomycin QID for 10d **Severe** → Vancomycin QID for 10d **Alternatives if ≥2 recurrences** → vancomycin po taper, fidaxomicin, FMT

Question 28

6 Things to Monitor

Answer 28

1. Resolution of signs/symptoms 2. Use of anti-motility agents and laxatives 3. Any new antibiotics started 4. Labs - WBC, electrolytes 5. Adherence 6. Adverse reactions

Question 29

Prevention

Answer 29

- Hand-washing with soap and water (hand sanitizer does not kill spores) - Use PPE when in contact with patient - Use single rooms and isolation for those suspected and confirmed - Environmental cleaning with specialized disinfectants

Question 30

Primary Prophylaxis

Answer 30

**Probiotics** → Theoretically prevent CDI by enhancing colonization resistance, mucosal barrier, neutralize CDI toxins and virulence or growth (caution against immunocompromised) - Lacks evidence

Question 31

Secondary Prophylaxis

Answer 31

**Probiotics** → Lacks evidence **Vancomycin BID for 10d + 1 week after** → recommended if multiple recurrences or severe complicated CDI and need antibiotics to treat for other bacterial infections