What are the stool tests for Clostridioides difficile infection (CDI)?

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From the Guidelines

Stool tests for Clostridioides difficile infection (CDI) should primarily use nucleic acid amplification tests (NAATs) or a two-step algorithm combining glutamate dehydrogenase (GDH) antigen detection with toxin enzyme immunoassay (EIA). When considering the diagnosis of CDI, it is crucial to understand the strengths and limitations of each testing method.

Key Considerations for CDI Diagnosis

  • NAATs offer high sensitivity but may detect colonization without active disease, as they identify the genetic material of the bacteria rather than the toxins it produces 1.
  • A two-step algorithm using GDH antigen detection followed by toxin EIA can provide a balance between sensitivity and specificity, helping to differentiate between colonization and active infection.
  • The choice of test should be guided by the clinical presentation of the patient, with only diarrheal stools being suitable for testing.
  • Testing for cure after treatment is not recommended, as patients can remain positive for weeks despite clinical improvement 1.
  • Repeat testing within 7 days of a negative test is generally unnecessary unless symptoms significantly worsen.

Recommendations for Practice

  • For initial diagnosis, use either a NAAT alone or a combination of GDH and toxin EIA.
  • Ensure that only diarrheal stools are tested, as formed stools do not require testing for CDI.
  • Avoid testing patients who have received laxatives in the 48 hours prior to testing, as this can lead to false positives.
  • Consider the clinical context and patient symptoms when interpreting test results, as the presence of C. difficile toxins correlates with clinical disease, while detection of the organism alone may represent colonization 1.

From the Research

Stool Tests for Clostridioides difficile Infection (CDI)

The following stool tests are used to diagnose CDI:

  • Toxin A/B enzyme immunoassay (EIA) 2, 3, 4, 5
  • Glutamate dehydrogenase (GDH) enzyme immunoassay (EIA) 2, 3, 4, 6, 5
  • Nucleic acid amplification test (NAAT) 2, 3, 4, 6, 5
  • Toxigenic culture 2, 6

Test Performance Characteristics

The performance characteristics of these tests vary:

  • Toxin A/B EIA: sensitivity 53-86.1%, positive predictive value (PPV) 58.4% 2, 4
  • GDH EIA: sensitivity 100%, PPV not specified, but may yield inconclusive results 2
  • NAAT: sensitivity 95%, PPV not specified, but may lead to overdiagnosis of CDI 3, 4, 6

Diagnostic Algorithms

A two- or three-step algorithm is recommended for optimal CDI detection:

  • Screening test with high sensitivity (e.g. GDH EIA or NAAT) followed by a more specific test to detect free toxins (e.g. toxin A/B EIA) 3, 4, 5
  • Use of a multistep approach to CDI diagnosis, such as either GDH or NAAT followed by toxins A/B EIA, in conjunction with laboratory stewardship 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

How to: diagnose infection caused by Clostridium difficile.

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2018

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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