Can a patient have Clostridioides difficile (C. diff) infection with formed stool?

Can a Patient Have C. difficile Infection with Formed Stool?

No, diagnostic testing for Clostridioides difficile infection (CDI) should only be performed on unformed stool samples from symptomatic patients, as testing formed stool can result in false positive results that may lead to unnecessary antibiotic therapy. 1, 2

Diagnostic Criteria for CDI

• CDI diagnosis requires both clinical symptoms and a positive laboratory test, with diarrhea defined as passage of three or more unformed stools in 24 hours 1
• Testing should be restricted to unformed stool samples to avoid false positive results that may represent asymptomatic colonization rather than active infection 1, 2
• Clinical guidelines from IDSA/SHEA specifically recommend that patients with unexplained and new-onset ≥3 unformed stools in 24 hours are the preferred target population for testing 1
• Since C. difficile can colonize the intestinal tract of healthy individuals, testing formed stool can detect colonization rather than infection 1

Why Testing Formed Stool Is Problematic

• Testing formed stool can result in false positive tests, particularly with highly sensitive nucleic acid amplification tests (NAATs), leading to unnecessary antibiotic therapy 1
• The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines indicate that restricting CDI testing to unformed samples does not cause the diagnosis of CDI to be missed 1
• Laboratory protocols typically include rejection policies for formed stool specimens to prevent overdiagnosis 1
• Clinicians should utilize clinically agreed-upon symptoms and appropriate diarrheal history before ordering C. difficile testing 1

Special Circumstances

• For patients with suspected severe CDI complicated by ileus who may be unable to produce stool specimens, perirectal swabs may provide an acceptable alternative with high sensitivity (95.7%) and specificity (100%) 1
• In these cases, testing is not performed on formed stool but rather on a different specimen type due to the patient's inability to produce diarrheal stool 1

Recommended Testing Approach

• Diagnostic testing should be performed only on diarrheal stools from symptomatic patients with clinically significant diarrhea (≥3 loose stools in 24h) with no obvious alternative explanation 1
• A two-step testing algorithm is recommended to increase diagnostic accuracy, using either:
  • GDH plus toxin EIA 1, 2
  • GDH plus toxin, arbitrated by NAAT 1
  • NAAT plus toxin 1
• Clinical context is crucial for interpretation, including recent antibiotic use, hospitalization history, and symptoms such as fever, abdominal pain, and leukocytosis 1, 2

Common Pitfalls to Avoid

• Testing formed stool samples, which can lead to detection of asymptomatic colonization rather than active infection 1, 2
• Testing patients on laxatives, which can cause diarrhea unrelated to CDI 1
• Repeat testing within 7 days during the same episode of diarrhea, which is not recommended 1
• Using a single test alone, especially toxin EIA, which has limited sensitivity 2

In conclusion, while C. difficile can colonize the intestinal tract without causing symptoms, true CDI is characterized by diarrhea. Testing formed stool is not recommended as it can lead to false positive results and unnecessary treatment.