Therapeutics III: Exam 3 - C. Difficile

What is C. difficile?

Gram-positive, spore forming, anaerobic cocci

NORMAL to the GI tract

Infection due to ingestion of spores or disruption of the GI flora

Toxin producing strains cause disease

When should diagnostic testing for C. diff be considered?

In patients with ≥ 3 episodes of diarrhea per day for >48h

Testing should not be performed on solid stool or patients currently on laxatives

What are characteristics of NAAT and PCR tests for C. diff?

Tests for gene that is responsible for toxin production

Cannot be used alone

Will be persistently positive for weeks following infection

Positive PCR alone frequently results in over treatment

What are characteristics of EIA tests for C. diff?

Tests for presence of toxin A or B

But toxin degrades quickly in stool samples

What are characteristics of GDH tests for C. diff?

Test for enzyme produced by all strains of C. difficile

How is diagnostic testing performed for C. diff?

Typically a multi-step process

Usually PCR followed by an EIA toxin test

What are risks for C. diff?

ANY antibiotic within past 3 months (esp. w/ polypharmacy and long duration)

Hospitalization within last 3 months or first year in a long-term care facility

Chemotherapy

GI surgery

Age ≥ 65

Inflammatory bowel disease

Hypoalbuminemia

Use of PPIs (and H2 antagonists to a lesser extent)

What antibiotics carry the most risk of C. diff?

Clindamycin > fluoroquinolones > 3rd/4th gen cephs > penicillins and carbapenems > others

What is severe C. diff infection (CDI) defined as?

WBC > 15,000, OR

SCr > 1.5

What is fulminant C. diff infection (CDI)?

Severe CDI

With hypotension/shock, ileus, or toxic megacolon

Rare, but extremely high mortality risk

Usually requires colectomy

What does treatment of C. diff depend on?

Dependent on severity and episode recurrence

Should asymptomatic patients that test positive for C. diff be treated with antibiotics?

NO

Asymptomatic patients with positive tests do not require treatment

Is empiric treatment prior to test results necessary in C. diff?

NO

EXCEPT - if suspected fulminant disease

What should be done with antibiotics in patients with C. diff?

D/C the inciting antibiotics whenever possible

Continuation of non-CDI antibiotics significantly increases the risk of treatment failure and recurrence

May not always be an option

Instead switch to a lower risk agent

What treatment is preferred for the 1st episode of C. diff, that is non-severe?

Fidaxomicin 200mg po BID x10 days

What are alternative treatments for the 1st episode of C. diff, that is non-severe?

Vancomycin 125mg po QID x10 days

If unable to access Vanco or Fidaxomicin: Metronidazole 500mg po TID for 10-14 days may be used

What treatment is indicated for the 1st episode of C. diff, that is severe?

Fidaxomicin 200mg po BID x10 days

OR

Vancomycin 125mg po QID x10 days

What treatment is indicated for the 1st episode of C. diff, that is fulminant?

Vancomycin 500mg PO QID orally (and rectally if ileus)

PLUS

Metronidazole 500mg IV q8h

What is the duration of treatment with Vancomycin or Fidaxomicin for the 1st episode of C. diff?

10 days

What is the difference between Fidaxomicin and Vancomycin for treatment of C. diff?

Same cure rate

Lower risk of recurrence with Fidaxomicin

When is Metronidazole used for C. diff therapy?

Acceptable only if other agents are not accessible

Due to higher failure rates than other agents (~25%+)

Or combo with Vanco for fulminant CDI

What are risk factors for recurrent C. diff infections?

Initial severe episode

Age

Continued (or future) antibiotics

20% after first episode, 40% after first recurrence, 60% after two or more recurrences

What treatment is indicated for the 1st recurrent episode of C. diff?

Fidaxomicin 200mg BID x10 days OR BID x5 days followed by q48h x20 days

Vancomycin 125mg po QID x10 days then taper (BID x7 days, QD x7 days, and then q48h for 2 to 8 weeks)

Consider adding Bezlotoxumab during treatment course

What treatment is indicated for the 2nd recurrent episode of C. diff?

Fidaxomicin 200mg BID x10 days OR BID x5 days followed by q48h x20 days

Vancomycin 125mg po QID x10 days then taper (BID x7 days, QD x7 days, and then q48h for 2 to 8 weeks)

Vancomycin 125mg po QID x10 days then Rifaximin 400mg TID x20 days

Consider adding Bezlotoxumab during treatment course

Fecal Microbiota Transplant (FMT)

What is Bezlotoxumab?

Single dose intravenous -mab with long T ½ that binds toxin B

Decreased recurrence in 12 week period

Increased CHF exacerbations among those with underlying heart failure

Recently discontinued in US market, remains FDA approved and available outside US

What are strategies for C. diff prevention in healthcare settings?

Antimicrobial stewardship

- Document the indication and set a definite length of therapy

- Restrict clindamycin and/or quinolones

Contact precautions: Gloves and gowns, dedicated equipment appropriate room disinfection

Wash hands (before & after) with soap & water for providers and visitors (spores not killed by alcohol gels)

What are strategies for C. diff prevention at home?

Clean bathrooms, replace toothbrushes

Probiotics are not recommended