# Toxic Megacolon With a Positive Clostridioides difficile Antigen but Negative Toxin Assay

**Authors:** Milikyas A Feyisa

PMC · DOI: 10.7759/cureus.103324 · Cureus · 2026-02-09

## TL;DR

An elderly man with a positive C. difficile antigen test but negative toxin assay developed severe toxic megacolon, highlighting limitations in diagnostic testing for severe CDI.

## Contribution

This case emphasizes the need to prioritize clinical judgment over conflicting lab results in severe C. difficile infections.

## Key findings

- A patient with a positive C. difficile antigen but negative toxin assay developed toxic megacolon.
- Toxin enzyme immunoassays may lack sensitivity in severe CDI cases.
- Clinical and radiological findings should guide treatment when lab results are discordant.

## Abstract

The diagnosis of Clostridioides difficile infection (CDI) relies on a combination of clinical presentation and laboratory testing. However, a critical diagnostic discordance occurs when laboratory results contradict a rapidly evolving clinical picture. This is a case of a 78-year-old man with four comorbidities who presented with watery diarrhea and a C. difficile screen-positive but toxin-negative stool sample. His main risk factors included advanced age and the prolonged use of a proton pump inhibitor. Despite his initial negative toxin assay, his condition progressively worsened over three days following his admission, with the development of toxic megacolon, diagnosed clinically and radiologically. This report synthesizes evidence on the limitations of toxin enzyme immunoassays in severe CDI, contextualizing a well-documented, but dangerously overlooked, phenomenon where test sensitivity fails in the sickest patients. This case highlights the imperative to treat the patient, not the lab result, when clinical and radiological evidence suggests fulminant disease.

## Linked entities

- **Diseases:** toxic megacolon (MONDO:0002105)
- **Species:** Clostridioides difficile (taxon 1496)

## Full-text entities

- **Diseases:** CDI (MESH:D003015), Toxic Megacolon (MESH:D008532), diarrhea (MESH:D003967)
- **Species:** Homo sapiens (human, species) [taxon 9606], Clostridioides difficile (species) [taxon 1496]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12980104/full.md

## References

11 references — full list in the complete paper: https://tomesphere.com/paper/PMC12980104/full.md

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Source: https://tomesphere.com/paper/PMC12980104