Clostridioides (Clostridium) difficile infection (CDI)

[Am J Gastroenterol 2021;116:1124-47, Clin Microbiol Infect 2021;27:S1-21, JAMMI 2018;3:71-92, Clin Infect Dis 2018;66:987-94]


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Definition: presence of unexplained and new-onset diarrhea (≥ 3 unformed stools in ≤ 24 hours) and either:

  • stool positive for toxigenic Clostridioides difficile and its toxins

  • colonoscopic or histopathologic findings of pseudomembranous colitis.

- Major risk factors for development of CDI: Treatment with antibiotics, proton pump inhibitors (PPIs), or antineoplastic agents within previous 8 weeks.


Infection Control:

- Hospitalized patients with suspected/confirmed CDI should be isolated with contact precautions.

- Strict adherence to handwashing (soap and water preferred; alcohol does not kill C. difficile spores).



- Discontinue systemic antibiotics if possible, especially clindamycin, quinolones (risk: moxifloxacin>ciprofloxacin>levofloxacin [CMAJ 2008;179:767-72]), and cephalosporins, as these agents have been associated with the highest risk of CDI. If not possible, consider changing to lower CDI risk group of antibiotics if appropriate (e.g. aminoglycosides, TMP/SMX, tetracyclines, and/or metronidazole).

- Assess whether other medications contributing to CDI or diarrhea can be discontinued: laxatives, stool softeners, pro-motility agents, PPIs/H2 blockers.

- Antimotility agents should be avoided in untreated CDI and in fulminant CDI.

- Probiotics are NOT recommended:

  • in the prevention of CDI in patients on antimicrobial therapy,


  • in the treatment of CDI.
  • Probiotics pose a risk of bacteremia/fungemia in immunocompromised patients.

Therapy of CDI:

- Vancomycin IV NOT effective. Metronidazole IV of uncertain efficacy (only use if very strict NPO, or in combination with vancomycin for fulminant CDI).

- Fecal microbiota transplant (FMT) may be considered if:

  • 2 or more episodes of CDI, both requiring hospitalization
  • 3 or more episodes of CDI
  • Fulminant CDI.

   Consultation with specialist recommended.



- Do not submit post treatment stool sample if asymptomatic and/or formed stools as toxin may persist for weeks post treatment.


Prevention of recurrent CDI:

[Am J Gastroenterol 2021;116:1124-47]

- Consider oral vancomycin prophylaxis (125mg PO daily for duration of systemic antibiotic use plus 5 days) to prevent further recurrence during subsequent non-CDI systemic antibiotic use in patients who are at high risk of recurrence:

  • patients hospitalized for severe CDI in past 3 months

    AND either:

  • 65 years or older, or
  • immunocompromised. 

- Prevention of CDI with metronidazole is NOT recommended due to potential for toxicity and lack of evidence of efficacy.