C. diff Infection

Table of Contents

Table of Contents

Published September 2021

Yilin Zhang, MD1

1 Assistant Professor, Department of Medicine, Valley Medical Center


  1. Identify risk factors for C. diff infection (CDI).
  2. Diagnose a patient with CDI and recognize the values and limitations of different tests.
  3. Differentiate between non-severe, severe, fulminant, and recurrent CDI. 
  4. Manage a patient with non-severe and severe CDI. Manage a patient with recurrent CDI. 

Teaching Instructions

Plan to spend at least 20 minutes preparing for this talk by using the interactive board for learning/preparing, clicking through the graphic, and becoming familiar with the order of the content that appears on the graphic. The teaching script below details how to walk through the talk. Every interactive or “clickable” element is denoted with a rounded box and cursor icon.

Anticipated time to deliver the talk with and without cases or other features: without cases 15 minutes. The cases may take an additional 10-15 min.

The talk can be presented in two ways:
1. Project the “Interactive Board” OR
2. Reproduce your own drawing of the presentation on a whiteboard.

Objective 1 (Epi and RF): Identify risk factors for C. diff infection.  

  • Highlight the difference between C. diff colonization and infection. There are high rates of C. diff colonization in the community and even higher in hospitalized patients. Stress the importance of only assessing for C. diff in patients with symptoms suggestive of infection.
  • Rates of community acquired CDI are rising – ~40% of all cases. Go through risk factors for CDI and which ones are associated with community acquired CDI. 

Objective 2 (Diagnosis): Diagnose a patient with CDI and recognize the values and limitations of different tests.

  • Evaluate for CDI in patients with risk factors and new onset diarrhea (3 or more stools in 24 h) or patients with ileus.
  • A rectal swab can be used for diagnosis in patients with ileus. 
  • Initial testing is typically with GDH Ag and Toxin A/B PCR. Indeterminant/ discordant results then undergo confirmation C. diff NAAT (nucleic acid amplification test).  Click on each of the tests to go over strengths and limitations of each test. 

Objective 3 (Definitions): Differentiate between non-severe, severe, fulminant, and recurrent CDIs.

  • Both IDSA and ACG guidelines define severe CDI as patients with WBC > 15k or Cr > 1.5 mg/dL on presentation. There are other signs that had previously been used to define severity such as abdominal tenderness and low serum albumin, which can clinically help support a severe infection. 
  • Fulminant infections are those that meet criteria for severe CDI and are additionally associated with hypotension/shock or ileus/megacolon. 
  • Recurrent CDI occurs in ~20% of patients. It commonly occurs in the first few weeks after the initial episode but can occur as late as 8 weeks after. 

Objective 4 (Treatment): Manage a patient with non-severe, severe, and recurrent CDI. 

  • 2021 IDSA updated guideline recommends fidaxomicin over vancomycin as first line for non-severe or severe CDI. 2021 ACG guidelines more strongly recommend fidaxomicin, though both fidaxomicin and vancomycin are considered first line for non-severe and severe CDI. 
  • PO metronidazole should only be considered in patients who are low risk and have non-severe CDI. 
  • Fulminant CDI should be treated with high dose PO vancomycin. PR vancomycin should be used in patients with ileus. IV metronidazole may lower mortality and can be used concurrently. Surgery should be considered in patients who do not improve. Fecal microbiota transplant (FMT) can be considered in patients who are not surgical candidates.
  • Recurrent CDI treatment depends on which recurrence.
    • Guideline updates more strongly recommend fidaxomicin over standard course vancomycin for 1st recurrence. This is based on new studies that have shown lower risk of recurrence with fidaxomicin. Pulse-dosed PO vancomycin is another alternative. 
    • Subsequent recurrences should be referred for consideration of FMT. 
    • Bezlotuxumab is a new monoclonal therapy that has been shown to decrease risk of recurrence. It is given as a single infusion. 

Prevention: Review precautions in the hospital as well as different suggested therapies for prophylaxis/prevention of CDI. There is a potential role for prophylactic low dose vancomycin in high-risk patients on systemic antibiotics. 

Presentation Board

Take Home Point

  1. Risk factors for CDI include older age, recent hospitalization and antibiotic exposure. However, community acquired CDI is becoming more common and patients with underlying IBD, cardiac disease, CKD are especially at risk. 
  2. Colonization is common so only patients with active symptoms should be tested for CDI. 
  3. Stool GDH Ag and toxin PCR can be used to test for active CDI. When these results are discordant, C. diff NAAT should be sent to confirm or exclude CDI. 
  4. Patients with severe CDI are defined as having WBC > 15k or Cr > 1.5 mg/dL. 
  5. Fidaxomicin is now the preferred treatment for non-severe, severe, or recurrent CDI. PO vancomycin is also considered acceptable first line therapy. 


  1. Kelly CR, et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol. 2021; 116: 1124-1147. 
  2. Johnson S, et al. Clinical Practice Guideline by 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. 2021. 31(4): e1029-e1044.
  3. McDonald LC, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA), Clinical Infectious Diseases. 2018. 66(7): e1–e48
Yilin Zhang


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