Exam 4: C. diff Flashcards
What is the structure of C. diff?
Gram-positive, spore forming, obligate anaerobic bacillus
(gram + rod that can form spores)
What is the more virulent strain of C. diff?
BI/NAP1/027
(higher severity and mortality)
How is C. diff transferred from person-to-person?
Fecal-Oral Route through ingestion of spores
What are the 3 main risk factors for C. diff infection?
Antibiotic exposure
Healthcare exposure
Age >/= 65 years
What are other risk factors for C. diff?
Proximity to person with C. diff infection
Use of acid suppressing agents (PPI, H2RA)
Chemotherapy
Immunosuppression
GI surgery
What 4 antibiotic drug classes can cause C. diff to occur?
Fluoroquinolones
Clindamycin
3rd/4th gen Cephalosporins (ceftriaxone)
Carbapenems
What 2 antibiotic drug classes have the highest risk of causing C. diff?
Fluoroquinolones*
Clindamycin
What are the steps to C. diff infection and pathogenesis?
- Disruption of colonic microflora (gut microbiome normally suppresses C. diff colonization)
- Source and introduction of C. diff to the colon (if not already there)
- Multiplication of C. diff and toxin production
- Colon and rectal mucosa become edematous, erythematous with adherent, raised plaque-like pseudomembranes (yellow-white)
What are the 2 main symptoms of C. diff?
Profuse, watery, or mucoid green, foul-smelling diarrhea
Abdominal pain
What are the other signs of C. diff?
Fever
Leukocytosis
Hypoalbuminemia
Acute Kidney Injury
When should you test for a C. diff infection?
3 or more profuse, watery or mucoid green, foul-smelling stools in 24 hours
What are the testing methods used to test for C. diff infections? (these give the most sensitive results)
3 methods:
- Nucleic acid amplification test (NAAT) used alone
- Antigen test (GDH) + Toxin A/B test (use NAAT if these two tests come back with different answers)
- NAAT + Toxin A/B test
True or False: We should repeat testing for C diff after 7 days
False
-this has limited value and is not recommended
If the toxin test for C diff is negative what might this mean?
The c diff is not producing toxin and is not an infection
How do we define a non-severe C diff infection?
WBC </= 15,000/mcL
SCr < 1.5 mg/dL
How do we define a severe C diff infection?
WBC > 15,000/mcL
SCr > 1.5 mg/dL
How do we define a fulminant C diff infection?
Hypotension or shock
Ileus
Toxic megacolon
What are the 3 drugs that can be used in C diff treatment?
Oral Vancomycin
Fidaxomicin
Metronidazole (IV or PO)
What drug is considered the standard of care for C diff?
Oral vancomycin
-provides broad spectrum coverage
(takes everything out including good bacteria)
What are the benefits to using Fidaxomicin for C diff treatment?
Narrower spectrum than vanc
(leaves some good bacteria)
Higher rates of sustained response
When do we use metronidazole for C diff treatment?
*No longer recommended as first line agent
*Reserve for fulminant cases as an additional agent
What about oral vancomycin’s absorption makes it a good treatment for C diff?
It has very bad oral absorption, which means that it is more concentrated in the GI tract where C diff is
True or False: C diff is the only indication for oral vancomycin
True
What is the standard and fulminant dosing of oral vancomycin for c diff?
Standard: Vancomycin 125 mg po q6h
Fulminant: Vancomycin 500 mg po q6h
What are the 2 patient considerations with oral vancomycin?
Liquid version can have a bitter taste
This is a cheaper option for treatment
How is fidaxomicin dosed for C diff treatment?
Standard: Fidaxomicin 200 mg po q12h
What is the main reason why Fidaxomicin is not the first-line option for C diff?
Cost! (very expensive)
How does metronidazole’s absorption not make it a great drug for c diff?
Is orally absorbed very well (more systemic absorption)
*note that this makes it good for fulminant C diff
How is metronidazole dosed?
Standard: Metronidazole 500 mg po q8h
*Fulminant: Metronidazole 500 mg IV q8h
What dosage form of metronidazole is used for fulminant infections?
IV
How does the efficacy of metronidazole compare to the other treatment options for c diff?
Less efficacious
Higher risk for recurrence
How does the cost of metronidazole compare to the other available agents?
Least costly option
What are the treatment options for an initial non-severe c diff episode?
PO Fidaxomicin (preferred if able to afford)
PO Vancomycin
PO Metronidazole (only if others unavailable)
What are the treatment options for an initial severe episode of C diff?
PO Fidaxomicin
PO Vancomycin
What agents should be avoided in C diff treatment?
Peristaltic agents (loperamide)
*we do not want to stop the patient’s diarrhea because we want the toxins to pass out of the body and not build up in the colon
What is the general recommendation for treating a recurrent C diff infection?
Change something: either the drug or the dosing regimen
What treatment options are available for a patient who has had their first c diff recurrence?
In order of preference:
-Fidaxomicin 200 mg po q12h x 10 days
-Vancomycin 125 mg po q6h x 10 days
-Fidaxomicin 200 mg po q12h x 5 days, then 200mg po every other day x 20 days (extended dosing)
-Vancomycin tapered and pulsed regimen
note that if one of these were used for the initial episode you should choose a different option
What do we do for a second or subsequent CDI recurrence?
Use one of the options from the First CDI recurrence
*select a different treatment than what was previously used
What is the treatment recommendation for Fulminant C diff?
Vancomycin 500 mg po q6h (high dose)
+
Metronidazole 500 mg IV q8h
*note: if ileus is present consider adding vancomycin 500 mg via rectal instillation q6h
What are the risk factors for c diff recurrence?
Age >/= 65 years
Immunocompromised
Severe c diff
When do we consider a Fecal Microbiota Transplant (FMT) in c diff patients?
Three or more episodes of c diff
Poor response to initial antibiotic therapy
When would we consider Rebyota fecal microbiota suspension in C diff patients?
For prevention of recurrence following antibiotic treatment for recurrent c diff
When is Rebyota therapy given in a patients c diff therapy?
24-72 hours after treatment completion
How does Vowst therapy work?
Bacterial spore suspension
-modulate bile acid concentrations and restore fatty acids which results in resistance to C diff colonization and restoration of the gut microbiome
When would we consider using Vowst in c diff therapy?
Prevention of recurrence in patients following antibiotic treatment for recurrent c diff
How and when is Vowst dosed in C diff therapy?
4 capsules PO once daily x 3 days starting 2-4 days after treatment completion
What is a benefit to using Vowst therapy for c diff?
It is an oral therapy!
What is the moa of Bezlotoxumab in c diff therapy?
Monoclonal antibody targeting C. diff toxin B to neutralize its effect
When should we consider Bezlotoxumab therapy in C diff?
To prevent recurrence in patients at high risk
What is the dosage form of Bezlotoxumab and when is it given during treatment?
IV
*given during the course of cdiff treatment
Who should Bezlotoxumab be used with caution in?
CHF patients
