PHARM: Treatment of C. Diff

Question 1

How does C. difficile cause infection?

Answer 1

Toxin A and Toxin B

Question 2

What controls the transcription of Toxin A and B?

Answer 2

tcdR (positive regulator of transcription) and tcdC (negative regulator of transcription)

Question 3

What is the name of the particularly virulent C. diff strain?

Answer 3

NAP-1/027

Question 4

Why is NAP-1/027 so virulent?

Answer 4

lacks tcdC—leads to overexpression of toxins and a very serious infection

Question 5

What antibiotics are most associated with C. diff infection?

Answer 5

clindamycin (penicillins) and cephalosporins (fluoroquinolones)

Question 6

True or false: PPIs can predispose to C. difficile infection?

Answer 6

FALSE: studies do NOT show an association between recurrent CDI and duration/dose of PPIs

Question 7

What is first line for mild C. difficile infection?

Answer 7

Oral metronidazole

Question 8

When would you use Vancomycin in a C. difficile patient?

Answer 8

severe disease and in pregnant/lactating women

Question 9

Why can metronidazole not be used in Pregnant and Lactating women?

Answer 9

NOT in pregnant women (readily crosses placenta and can lead to facial anomalies), NOT in lactating women (increased oral and rectal Candida colonization and loose stools in infants)

Question 10

What are the toxicities of metronidazole?

Answer 10

10% of patients have nausea and a metallic taste; peripheral neuropathy after high dose/extended use

Question 11

What drug combination is recommended for complicated C. diff infections?

Answer 11

Vancomycin (PO) + Metronidazole (IV)

Question 12

How else can vancomycin be given (ex. if patient has ileus)?

Answer 12

Rectally

Question 13

MOA: inhibits bacterial RNA polymerases of C. difficile

Answer 13

Fidaxomicin

Question 14

What are the limitations of Fidaxomicin as an antibiotic?

Answer 14

NOT effective against GN anaerobes, facultative aerobes, and enterobacteriaceae; limited effect on normal fecal flora)

Question 15

Does Fidaxomicin have cross resistance with rifamycin?

Answer 15

NO cross-resistance with rifamycin (works on different site)

Question 16

What is unique about the pharmacokinetics of Fidaxomicin?

Answer 16

minimal systematization after oral administration (mainly remains in GI tract and is almost completely eliminated in the stool)

Question 17

Which is better for C. diff treatment, Fidaxomicin or Vancomycin?

Answer 17

“head to head” comparison with vancomycin in groups at high risk for CDI, fidaxomicin provides a superior clinical response and lower incidence of recurrence

Question 18

What is the most effective means of stool transfer?

Answer 18

colonoscopy

Question 19

Do fecal transplants work to treat C. diff?

Answer 19

YES: Recent studies of fecal microbiota transplantion have shown that almost 90% of patients had complete clinical resolution of CDI following fecal transplantation

Question 20

True or false: both donor and recipient are given antibiotics before stool trasnplant?

Answer 20

FALSE: donor can’t be on antibiotics and recipient must have their antibiotics stopped 2-3 days prior to transplant