When should C. difficile (Clostridioides difficile) be tested versus fecal pathogens in patients with diarrhea?

When to Test for C. difficile vs Fecal Pathogens in Patients with Diarrhea

C. difficile testing should be performed in patients >2 years of age with a history of diarrhea following antimicrobial use within the preceding 8-12 weeks or in those with healthcare-associated diarrhea, while fecal pathogen testing should be considered for community-acquired diarrhea with risk factors for specific pathogens. 1

Decision Algorithm for Diagnostic Testing

When to Test for C. difficile:

• Primary indications:

  • Age >2 years with diarrhea following antimicrobial use within the preceding 8-12 weeks
  • Healthcare-associated diarrhea
  • Persistent diarrhea without an identified etiology 1

• Risk factors increasing likelihood of C. difficile:

  • Age ≥75 years (2.2 times higher risk)
  • Hospitalization ≥7 days (2.3 times higher risk)
  • Recent exposure to certain antibiotics, particularly cefazolin (3.5 times higher risk) or levofloxacin (2.1 times higher risk) 2

When to Test for Fecal Pathogens:

• Community-acquired diarrhea with:

  • Fever
  • Bloody or mucoid stools
  • Severe abdominal pain
  • Recent travel
  • Food exposure history
  • Outbreak setting 1

• Specific pathogen testing based on clinical presentation:

  • Visible blood in stool: Test for STEC, Shigella, Salmonella, Campylobacter, E. histolytica
  • Persistent diarrhea (>14 days): Test for parasitic infections (Cryptosporidium, Giardia, Cyclospora)
  • Severe abdominal pain with minimal fever: Consider STEC, Salmonella, Campylobacter
  • Recent travel: Test based on travel destination and exposure history 1

Testing Methodology

For C. difficile:

• Use a single diarrheal stool specimen (one that takes the shape of the container)
• Do not test formed stool or asymptomatic patients
• Do not perform repeat testing within 7 days during the same episode of diarrhea 1
• Recommended testing methods:
  • Nucleic acid amplification test (NAAT)
  • GDH antigen with toxin detection
  • Two or three-stage algorithm (GDH plus toxin; GDH plus toxin, arbitrated by NAAT; or NAAT plus toxin) 1

For Fecal Pathogens:

• Fresh diarrheal stool sample is optimal
• For bacterial infections, a rectal swab may be used if timely stool collection is not possible
• Culture-independent diagnostic tests (CIDTs) like multiplex PCR panels can detect multiple pathogens simultaneously 1

Special Populations Requiring Broader Testing

• Immunocompromised patients: Test for a broader range of pathogens including Cryptosporidium, Cyclospora, Cystoisospora, microsporidia, Mycobacterium avium complex, and cytomegalovirus 1

• Travelers with persistent diarrhea (>14 days): Evaluate for intestinal parasitic infections and C. difficile if antibiotics were used 1

• Outbreak settings: Test for a broader set of bacterial, viral, and parasitic agents regardless of clinical presentation 1

Important Caveats

• Only test symptomatic patients; asymptomatic carriage of C. difficile is common, especially in hospitalized patients and children <2 years 1, 3

• Interpret multiplex molecular test results with caution as they detect DNA, not necessarily viable organisms 1

• Consider clinical presentation when interpreting test results, as no single test is perfect for confirming CDI 4

• In children <2 years, C. difficile testing is generally not recommended due to high rates of asymptomatic colonization 1

By following this evidence-based approach to testing, clinicians can appropriately diagnose infectious causes of diarrhea while avoiding unnecessary testing, which can lead to improved patient outcomes and reduced healthcare costs.