C. diff

Question 1

Overview of C. diff

Answer 1

Gram-positive, spore-forming, anaerobic bacillus

Produces two toxins (TcdA–>inflammatory and TcdB–>cytotoxin)

BI/NAP1/027–> more virulent strain, higher severity

Question 2

Pathogenesis

Answer 2

Disruption of colonic microflora–>source & introduction of C. dificile to the colon–>
multiplication of C. dificile occurs and toxin production begins–>colon & rectal mucosa
becomes edematous, erythematous with adherent, raised plaque-like pseudomonas
(yellow-white)

Question 3

Transmission

Answer 3

person-to-person via fecal-oral route through ingestion of spores

Question 4

Risk factors

Answer 4

> or equal to 65
Healthcare exposure
Fluoroquinolone’s, clindamycin, 3rd/4th generation cephalosporins (ceftraixone), carbapenems
Proximity to person with C.diff infection
Chemo
Immunosuppression
PPI, H2RA
GI surgery

Question 5

Clinical presentation

Answer 5

Profuse, watery foul-smelling diarrhea
Abdominal pain

Question 6

Diagnosis

Answer 6

When to test? 3 or more profuse, watery foul-smelling stools in 24 hours

3 testing methods:
- Nucleic acid amplification test alone
- Antigen test (GDH) + Toxin A/B test
- NAAT + Toxin A/B test: used if 1 (+) and 1 (-)

Question 7

Non-severe

Answer 7

WBC ≤ 15,000 /mcL
SCr < 1.5 mg/dL

Question 8

Severe

Answer 8

WBC > 15,000 /mcL
SCr > 1.5 mg/dL

Question 9

Fulminant

Answer 9

Hypotension or shock
Ileus
Toxic megacolon–>medical emergency that requires surgery

Question 10

Oral Vancomycin

Answer 10

PK/PD: extremely poor absorption

Dosing:
- standard–> 125 mg PO q6h
- fulminant–> 500 mg PO q6h

Pearls: liquid version has better taste

Question 11

Fidaxomicin

Answer 11

PK/PD: extremely poor absorption, protein synthesis inhibitor

Dosing: Fidaxomicin 200 mg PO q12h

Pearls: Higher rates of sustained treatment response with lower recurrence rates

Cost is huge barrier

Question 12

Metronidazole (IV or PO)

Answer 12

PK/PD: excellent absorption > 90%

Dosing: 500 mg PO or IV q8h

Pearls: Less efficacious and higher risk of recurrence, least costly

Question 13

Initial episode, non-severe

Answer 13

1st: Fidaxomicin x 10 days
2nd: Vancomycin PO x 10 days
3rd: Metronidazole x 10 days

Question 14

Initial episode, severe

Answer 14

1st: Fidaxomicin x 10 days
2nd: Vancomycin x 10 days

Question 15

First recurrence

Answer 15

Change to fidaxomicin x 10 days
Change to vancomycin x 10 days
Fidaxomicin QD x 5 days, then fidaxomicin QOD x 20 days
Vancomycin tapered and pulsed

Question 16

Fulminant

Answer 16

Vancomycin + Metronidazole

If ileus present, add vancomycin via rectal instillation

Question 17

AVOID LOPERAMIDE

Question 18

Fecal Microbiota Transplant

Answer 18

Administration of fecal material from healthy person to restore a balanced gut microbiome

Used as both a treatment option and a method to reduce recurrence

3 or more episodes of CDI
Poor response to initial therapy

Administered via endoscopy, colonoscopy, or rectal tube

Question 19

Rebyota

Answer 19

Fecal microbiota suspension

Indication: prevention of recurrence of CDI for patients following antibiotic treatment for recurrent CDI

Dosing: 150 mL administered via rectal tube 24-72 hours after treatment completion

Question 20

Vowst

Answer 20

Bacterial spore suspension

Indication: prevention of recurrence of CDI for patients following antibiotic treatment for recurrent CDI

Dosing: 4 capsules PO once daily x 3 days starting 2-4 days after treatment completion

Question 21

Bezlotoxumab

Answer 21

Monoclonal antibody targeting C. diff toxin B to neutralize its effect

Prevention of recurrence of CDI for patients at high risk for CDI recurrence

Dosing: 10 mg/kg IV x dose during the course of CDI treatment

Caution in patients with CHF