PHARM: Treatment of C. Diff Flashcards
How does C. difficile cause infection?
Toxin A and Toxin B
What controls the transcription of Toxin A and B?
tcdR (positive regulator of transcription) and tcdC (negative regulator of transcription)
What is the name of the particularly virulent C. diff strain?
NAP-1/027
Why is NAP-1/027 so virulent?
lacks tcdC—leads to overexpression of toxins and a very serious infection
What antibiotics are most associated with C. diff infection?
clindamycin (penicillins) and cephalosporins (fluoroquinolones)
True or false: PPIs can predispose to C. difficile infection?
FALSE: studies do NOT show an association between recurrent CDI and duration/dose of PPIs
What is first line for mild C. difficile infection?
Oral metronidazole
When would you use Vancomycin in a C. difficile patient?
severe disease and in pregnant/lactating women
Why can metronidazole not be used in Pregnant and Lactating women?
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)
What are the toxicities of metronidazole?
10% of patients have nausea and a metallic taste; peripheral neuropathy after high dose/extended use
What drug combination is recommended for complicated C. diff infections?
Vancomycin (PO) + Metronidazole (IV)
How else can vancomycin be given (ex. if patient has ileus)?
Rectally
MOA: inhibits bacterial RNA polymerases of C. difficile
Fidaxomicin
What are the limitations of Fidaxomicin as an antibiotic?
NOT effective against GN anaerobes, facultative aerobes, and enterobacteriaceae; limited effect on normal fecal flora)
Does Fidaxomicin have cross resistance with rifamycin?
NO cross-resistance with rifamycin (works on different site)
What is unique about the pharmacokinetics of Fidaxomicin?
minimal systematization after oral administration (mainly remains in GI tract and is almost completely eliminated in the stool)
Which is better for C. diff treatment, Fidaxomicin or Vancomycin?
“head to head” comparison with vancomycin in groups at high risk for CDI, fidaxomicin provides a superior clinical response and lower incidence of recurrence
What is the most effective means of stool transfer?
colonoscopy
Do fecal transplants work to treat C. diff?
YES: Recent studies of fecal microbiota transplantion have shown that almost 90% of patients had complete clinical resolution of CDI following fecal transplantation
True or false: both donor and recipient are given antibiotics before stool trasnplant?
FALSE: donor can’t be on antibiotics and recipient must have their antibiotics stopped 2-3 days prior to transplant
