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Updated: Jan 18, 2026

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Diagnostic Approaches for Clostridioides difficile Infection.

Parul Berry1, Sahil Khanna2

  • 1Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.

Infectious Disease Clinics of North America
|September 7, 2025
PubMed
Summary

Accurate Clostridioides difficile infection (CDI) diagnosis requires testing only symptomatic patients. Multistep algorithms combining enzyme or nucleic acid amplification tests with toxin assays improve accuracy, distinguishing infection from colonization.

Keywords:
Clostridioides difficile infectionClostridioides difficile infection diagnosisDiagnostic stewardshipGlutamate dehydrogenaseMultistep testing algorithmPseudomembranous

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Area of Science:

  • Clinical Microbiology
  • Infectious Diseases
  • Diagnostic Medicine

Background:

  • Clostridioides difficile infection (CDI) poses a significant healthcare challenge.
  • Accurate diagnosis is crucial for effective patient management and preventing spread.
  • Distinguishing CDI from asymptomatic colonization is a key clinical challenge.

Purpose of the Study:

  • To provide a clinically focused overview of current Clostridioides difficile infection diagnostic strategies.
  • To emphasize the importance of testing symptomatic patients only.
  • To review and recommend evidence-based diagnostic algorithms for CDI.

Main Methods:

  • Review of current literature and guideline-based recommendations for CDI diagnosis.
  • Discussion of diagnostic algorithms, including glutamate dehydrogenase (GDH) testing, nucleic acid amplification tests (NAAT), and toxin assays.
  • Emphasis on the necessity of clinical correlation and the limitations of specific testing modalities.

Main Results:

  • Multistep diagnostic algorithms combining GDH or NAAT with toxin assays enhance diagnostic accuracy.
  • Nucleic acid amplification tests (NAAT) alone may overestimate CDI by detecting colonization.
  • Clinical correlation is essential to differentiate true infection from colonization.

Conclusions:

  • Testing should be reserved for patients with relevant clinical signs and symptoms of CDI.
  • A combination testing approach is recommended to improve specificity and clinical utility.
  • Adherence to guideline-based diagnostic strategies ensures optimal management of CDI.