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Review
. 2025 Sep 6:S0891-5520(25)00077-7.
doi: 10.1016/j.idc.2025.07.014. Online ahead of print.

Diagnostic Approaches for Clostridioides difficile Infection

Affiliations
Review

Diagnostic Approaches for Clostridioides difficile Infection

Parul Berry et al. Infect Dis Clin North Am. .

Abstract

This article offers a clinically focused overview of Clostridioides difficile infection (CDI) diagnosis, emphasizing the need to test only symptomatic patients and to distinguish true infection from colonization. It reviews multistep diagnostic algorithms that pair glutamate dehydrogenase (GDH) testing or nucleic acid amplification tests (NAAT) with toxin assays to improve accuracy. The limitations of PCR-only approaches are discussed, with a strong emphasis on clinical correlation. Guideline-based recommendations are integrated throughout, providing evidence-based direction for clinicians managing CDI in both inpatient and outpatient settings.

Keywords: Clostridioides difficile infection; Clostridioides difficile infection diagnosis; Diagnostic stewardship; Glutamate dehydrogenase; Multistep testing algorithm; Pseudomembranous.

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Conflict of interest statement

Disclosures S. Khanna: Research support from Rebioitx/Ferring, Switzerland, Vedanta, Seres, United States and Pfizer, United States. S. Khanna serves as a consultant for ProbioTech, Takeda and Rise. PB: None.