C. difficile Infection

Dr. Morelli - 1 LH

Define non-severe c-diff

Contrast to severe c-diff

-WBC & SCr values?

NON-SEVERE:

WBC ≤ 15,000 cells/mL

Serum creatinine < 1.5 mg/dL

Severe is the same values, but >, 15k WBC and ≥ 1.5 mg/dL…

When is c-diff considered fulminant?

when there is severe systemic disease

• hypotension

• shock

• ileus (no bowel movement/peristalsis)

• toxic megacolon

When is c-diff considered recurrent?

sx recur ~8 weeks after completing treatment

Discuss infection control measures for prevention of transmission of C.difficile infection:

• What kind of cleaning agents should be used?

chlorine-containing or sporicidal

When do we test patients for c-diff?

Only test symptomatic patients with with ≥ 3

loose stools in 24 hours

(many asymptomatic patients are colonized)

What is the most sensitive test for c-diff? What is the main drawback?

NAAT (PCR)… can’t differentiate infection vs colonization

What is the GDH antigen test best for?

ruling out if it’s not c-diff… (GDH antigen NEGATIVE means no c-diff… if positive, need toxin test)

What is the most specific test for c-diff?

Toxin A/B EIA

(used after GDH to confirm active disease)

(FYI) sensitivity vs specificity

sensitivity = ability of a test to correctly identify people WITH the disease

specificity = ability of a test to correctly identify people WITHOUT the disease

What are the 3 high risk antibiotics for c-diff?

1. clindamycin

2. 3rd gen cephalosporins

3. FQs

What is the first line drug (dose/duration) for an initial episode of non-severe c-diff?

• What is the alternative if $$ an issue?

• What is an alternative if can’t acquire either?

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

alternatively, vanco 125 mg PO QID x 10 days

-if can’t do either - metronidazole 500mg PO TID x 10 days

What is the first line drug (dose/duration) for an initial episode of severe c-diff?

same as non-severe MINUS metronidazole as an option!

Fulminant C. difficile infection treatment

• First-line antibiotic(s)?
• Dose, route, and frequency?
• Additional therapy if ileus present?
• Duration of therapy?

oral vanco + metronidazole IV

Vanco 500 mg PO QID + Metronidazole 500 mg IV q8h

If ileus present:
• Vancomycin 500 mg PR QID

• treat for 10–14 days

How do we treat the first recurrent episode of recurrent c-diff?

same as first line but followed by a taper/pulse regimen

how should we treat a second or later recurrence of c-diff?

first line tapers, switch to not used first line, or a fecal transplant

(FYI) classify Clostridioides difficile

gram-positive, anaerobic, spore-forming toxigenic bacillus

(spores problematic - bacteriocidals do not kill spores)

How is c-diff spread?

oral-fecal

What are the medication-related risk factors for c-diff?

PPIs > H2RAs… acid suppression

Would symptomatic c-diff be caused by a high or low serum antibody response to toxin A?

low…

MOA of fidaxomycin

RNA pol inhibition

fidaxomicin common AEs

N/V, ab pain, fevers/chills/fatigue

Warnings on fidaxomycin

• macrolide and soy allergy

(not to be used in systemic infection due to minimal systemic absorption)

What is the DD interaction of cyclosporine and fidaxomycin?

Cyclosporine increases plasma concentrations of fidaxomicin and may decrease concentrations in the GI tract because of P-gp inhibition (fidaxomicin is a P-gp substrate)

Notable DD interaction of PO vanco

bile acid sequesterants

List the 3 most common ADRs of metronidazole

1. neuropathy

2. nausea

3. taste disturbances

T/F - fecal microbiota transplants are more efficacious than first line antibiotics

true

What are the two FDA-approved live biotherapeutic products that are pretty much evolutions of a fecal transplant? Which one is rectal? Which is oral?

Rebyota = R for rectal

Vowst = PO

T/F - Patients need to follow up 2-6 weeks after CDI treatment for a negative stool sample

FALSE