San Francisco VA Medical Center Guidelines for the Treatment of Diarrhea Associated with Clostridioides difficile Infection (CDI)

Modified Date: 
October 26, 2021

San Francisco VA Medical Center Guidelines for the Treatment of Diarrhea

Associated with Clostridioides difficile Infection (CDI)



  • Presence of diarrhea defined as 3+ unformed stools within 24 hours
  • A stool test* for the presence of C. difficile toxin, OR the presence of pseudomembranous colitis on colonoscopic or histopathologic exam
    • The stool sample sent to the lab must be diarrheal and take the shape of the collection container, NOT formed stool.
    • If the patient has an ileus or clinical suspicion of toxic megacolon and no active diarrhea, a stool swab can be cultured or tested by toxin assay, but the lab must be notified.
    • Each patient is allowed a maximum of 1 toxin assay per week, given the high sensitivity of the test.
    • Testing for cure is NOT recommended.
  • Note that the majority of patients presenting with C. difficile colitis have a history of antibiotic use within the past 8 weeks, although this is not necessary to make the diagnosis.

*At VA, testing is for C. difficile toxin B by PCR

Classifying Severity of Disease


WBC < 15,000 & SrCr < 1.5 mg/dL


WBC > 15,000 OR SrCr > 1.5 mg/dL


Presence of hypotension, shock, ileus, or megacolon

Interpreting Laboratory Results

Adapted from: 

  • Cohen, Stuart H., et al. "Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA)." Infection Control & Hospital Epidemiology 31.5 (2010): 431-455.
  • Johnson, Stuart, et al. "Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 focused update guidelines on management of Clostridioides difficile infection in adults." Clinical Infectious Diseases 73.5 (2021): e1029-e1044.


CDI Treatment Regimens

Initial CDI episode

Mild /Moderate/ Severe

Vancomycin 125 mg PO q6h x10 days




Fidaxomicin 200 mg PO q12h for 10 days for patients at increased risk of CDI recurrence:

  • Age > 65 years old
  • Concomitant antibiotic use during CDI treatment
  • History of inflammatory bowel disease

Fulminant CDI

Vancomycin oral solution 500mg PO q6h.

If ileus is present, add metronidazole 500mg IV q8h and consider Vancomycin 500mg in 100ml normal saline given as a retention enema q6h.  Therapy should be followed by a vancomycin taper (see below).  ID or GI and surgical consultation should be obtained for severely ill patients.

1st Recurrence

Fidaxomicin 200 mg PO q12h for 10 days

≥ 2nd Recurrence

Vancomycin oral solution in a tapered regimen:


Vancomycin PO 125mg PO q6h x14 days, then 125mg PO q12h x7 days, then 125mg PO daily x7 days, then 125mg PO every other day x7 days, then 125mg every 3rd day x14 days




Evaluate for fecal microbiota transplant (FMT)


Patient Selection for FMT: Must meet one of the following criteria:

  1. Patients with at least 3 recurrences of CDI and has failed standard of care treatment
  2. Patients with at least 2 recurrences of CDI with any episodes requiring hospitalization

CDI Prophylaxis Agents


10 mg/kg IV single dose


Infectious Diseases Section approval is required


Initial episode: Toxin antigen protein positive AND meets one of the following:

  • Hematologic cancer with neutropenia (ANC < 500) expected > 30 days
  • Recent bone-marrow transplant or treatment for GVHD
  • Solid-organ transplant < 3 months
  • Patient does not have history of heart failure


1st recurrence: If recurrence occurred within previous 6 months

2nd recurrence: All patients


  • Given as a single, life-time dose.
  • Must be administered during CDI treatment course.
  • May be administered as in outpatient in the infusion center
  • Patients with underlying congestive heart failure are at higher risk of mortality due to cardiac failure, reserved for use when the benefit outweighs the risk.


125 mg PO q12h




Must meet ALL of the following criteria:

  • Recurrent episode of CDI within the past 6 months
  • Patient requires treatment with antibiotics (beta-lactams, quinolones, or clindamycin) not directed against CDI in the inpatient setting
  • No history of vancomycin allergy

Initiate as soon as a patient is identified as a candidate and continue until antibiotics not directed against CDI are discontinued

Points to Consider

-If an inciting antimicrobial is suspected (most commonly clindamycin, aminopenicillins, third-generation cephalosporins, and fluoroquinolones), discontinue the agent as soon as possible.

-The use of antimotility agents (loperamide, etc.) should be avoided.

-If severe or fulminant disease is suspected, initiate empiric treatment while awaiting assay results. If the assay is negative, use clinical judgment when deciding if therapy should be discontinued.

-Use caution with high dose oral/rectal vancomycin (500mg Q6H) in patients with renal insufficiency, as significant absorption can occur in the setting of colitis and systemic accumulation could lead to ototoxicity, nephrotoxicity, or other adverse effects.

-Always wash hands with soap and water after examining a patient with suspected/confirmed C. difficile, as alcohol based sanitizers do NOT kill spores.

-Patients should remain on contact isolation until no diarrhea for 24 hours.

- FMT is administered via capsules from ID Clinic in non-hospitalized patients