Module 9: C. diff TRAT

Question 1

How does C. diff cause harm?

Answer 1

-Toxin A and B

-pro-inflammatory
-toxic to cells of the colon (cytotoxic)

Colonocyte death -> loss of intestinal barrier function -> Colitis

Question 2

Which strain of C. diff is known to have an increased risk of mortality?

Answer 2

-NAP-1 strain (can be tested for in the hospital)

-hypervirulent
-produces more toxin

Question 3

Common signs of C. diff

Answer 3

-Abdominal discomfort
-diarrhea
-fever
-Leukocytosis
-toxic megacolon (when untreated)

Question 4

When should a C. diff infection be considered?

Answer 4

-history of antibiotic use (3 months)
-diarrhea within 72 of hospitalization (but also evaluate if they have other reasons for diarrhea -> other drugs causing diarrhea Senna, docusade, laxatives)

Question 5

Risk factors of a C. diff infection

Answer 5

-antimicrobial exposure (disruptive GI flora)
-advanced age
-prolonged hospitalization
-chemotherapy/immunosuppression
-GI surgery
-tube feeding
-PPIs > H2RA

Question 6

Which antibiotics are frequently associated with C. diff?

KNOW

Answer 6

-broad spectrum

-FQ
-Clindamycin
-Penicillins
-Cephalosporins

Question 7

Which antibiotics are occasionally associated with C. diff?

KNOW

Answer 7

-Macrolides
-Bactrim

rare:
-Aminoglycosides
-Vancomycin (treats C. diff)
-Metronidazole (treas C. diff)
-Tetracyclines

Question 8

When to test for C. diff

Answer 8

-more than 3 unexplained unformed stools within 24 hrs
-it has to be unexplained (it could be caused by drugs)

-testing patients who are asymptomatic with a history of C. diff is NOT appropriate -> might be positive for weeks or months

Question 9

How are patients tested for C. diff?

Answer 9

-antigen test: testing for GDH and NAAT -> C. diff in the colon

-stool-toxin test: tells if the C. diff is pathogenic and warrants treatment

-asymptomatic patients with a history of C. diff will probably have a positive antigen test but the stool test will be negative

-no point in testing asymptomatic patients

Question 10

What is the recommended treatment for C. diff in an initial episode (first time)

IDSA Guidelines 2021

Answer 10

1st line: Fidaxomicin 200 mg PO BID x 10 days

2nd line: Vancomycin 125 mg PO 4x daily - often seen as 1st line because FDX is expensive

3rd line: Metronidazole 500 mg PO daily x 10 days (only if Fidaxomicin/Vanc fails) -> higher failure and recurrence rate

Question 11

What is the recommended treatment for C. diff in a fulminant phase?

IDSA Guidelines 2021

Answer 11

2 routes necessary

-Vancomycin 500 mg PO daily - 4d (+rectal Vanc if the colon is paralyzed (ileus))
+
-Metronidazole 500 mg IV q8h

Question 12

How would a patient present in a fulminant phase?

Answer 12

patients with hemodynamic instability: hypotension, shock, ileus (paralyzed colon), megacolon

Question 13

What is the recommended treatment for C. diff in the 1st recurrence?

IDSA Guidelines 2021

Answer 13

Fidaxmicin 200 mg PO BID x 10 d
or 200 mg BID x 5d and q48h for 21 d

2nd line:
Vanc 125 mg PO 4x daily x 10d or tapered regimen

Adjunctive: Bezlotoxumab 10mg/kg IV once together with FDX/Vanc -> to prevent recurrence

Question 14

What is the recommended treatment for C. diff in the 2nd recurrence?

IDSA Guidelines 2021

Answer 14

Fidaxmicin 200 mg PO BID x 10 d
or 200 mg BID x 5d and q48h for 21 d

2nd line:
Vanc 125 mg PO 4x daily x 10d, then rifaximin 400 mg PO TID x 20 days OR Vanc in a tapered regimen

-fecal microbiota transplant

Adjunctive: Betoloxumab 10mg/kg IV once with FDX/VNC

Question 15

MOA of Fidaxomicin

Answer 15

-Macrolide (CAUTIN in macrolide allergy)
-inhibits RNA polymerase sigma unit -> inhibition of protein synthesis

-minimal systemic absorption
200 mg PO BID x 10 days

Question 16

What is the idea of VNC taper and pulse dosing?

Answer 16

-allowing the dormant spores to become active and killed every 2-3 days
-helps in restoring the normal gut flora

Question 17

MOA of Betoloxumab

Answer 17

binds and neutralizes the C. diff toxin B

Question 18

When should Betoloxumab be taken?

Answer 18

Betoloxumab (Zinplava)

recommended by the IDSA guidelines
-for patients with recurrent C. diff episodes within the last 6 months

-dose: 10 mg/kg IV together with FDX/VNC

-CAUTION: higher rates of heart failure in patients with cardiac disease

Question 19

Which patient population should use Betoloxumab with caution?

Answer 19

higher rates of heart failure in patients with cardiac disease

Question 20

How does a patient present with antibiotic-associated diarrhea?

Answer 20

-secondary to change in intestinal flora after antibiotic use

-loose stools
-minimal signs of colitis

-no systemic signs of an infection
-no constitutional symptoms like fever, leukocytosis -> seen in C. diff infection

Question 21

How to treat patients present with antibiotic-associated diarrhea?

Answer 21

-supportive measures (hydration, probiotics, anti-diarrheal agents)

-antibiotic withdrawal (if possible)

Question 22

Which bacteria commonly cause Traveler’s diarrhea?

Answer 22

Traveler’s diarrhea (foodborne illness)

-Enterotoxigenic E. coli (ETEC)
-Shiga-toxin-producing E. coli (STEC/ Enterohemorrhagic E. coli)

Question 23

Which E. coli strain should NOT be treated with antibiotics?

Answer 23

Shiga-toxin-producing E. coli (STEC/ Enterohemorrhagic E. coli)

Question 24

Therapy for traveler’s diarrhea

Answer 24

Signs: watery diarrhea (more than 3 loose stools in 24 hr)

mild-moderate: supportive care

-severe:
*FQ for 1-3 days (for both E. coli or C. jejuni)
*C. jejuni: Azithromycin
*E. coli: Rifaximin

Question 25

When is a FQ recommended for traveler’s diarrhea?

Answer 25

-when the causing bacteria is not known and the patient can’t be tested
-it targets and Campylobacter jejuni and E. coli

Question 26

When should anti-diarrheals NOT be used?

Answer 26

in a C. diff infection -> the body tries to get rid of the bacteria
-use it in non-CDI if dehydration is a concern

Loperamide (Imodium)
Diphenoxylate and atropine (Lomotil)
Psyllium