A two-stage algorithm for Clostridium difficile including PCR: can we replace the toxin EIA?

Area of Science:

• Clinical microbiology
• Infectious disease diagnostics
• Gastroenterology

Background:

• Clostridium difficile infection (CDI) diagnosis relies on sensitive and specific methods.
• Current diagnostic algorithms aim to balance speed, accuracy, and cost-effectiveness.
• Identifying all cases of toxigenic C. difficile is crucial for effective patient management.

Purpose of the Study:

• To evaluate a two-step, three-test diagnostic algorithm for Clostridium difficile infection (CDI).
• To assess the algorithm's ability to identify patients with detectable toxin A/B and those with sub-detection levels of toxigenic C. difficile.

Main Methods:

• Stool samples were tested using enzyme immunoassays for C. difficile common antigen (glutamate dehydrogenase, G) and toxins A/B (T).
• Samples with discordant results (G(+)T(-)) were further tested by polymerase chain reaction (PCR) for the toxin B gene (P).
• This resulted in a three-test algorithm: G/T EIA, followed by PCR if results were discordant (G(+)T(-)P(+)).

Main Results:

• The algorithm rapidly identified patients with detectable C. difficile toxins A/B (G(+)T(+)).
• A significant group of patients with toxigenic C. difficile but below-detection toxin levels (G(+)T(-)P(+)) were identified separately.
• Patients with G(+)T(+) results had a higher average white blood cell count compared to those with G(+)T(-)P(+) results.

Conclusions:

• The reviewed algorithm efficiently detects CDI patients with high toxin levels.
• It also identifies patients with toxigenic C. difficile strains that may not produce detectable toxins, aiding in comprehensive CDI diagnosis.
• Differences in white blood cell counts suggest distinct clinical presentations or severity between these diagnostic groups.