What are two stool tests for Clostridioides difficile (C. diff) and two reasons why the hypervirulent strain is considered hypervirulent?

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From the Guidelines

Clostridium difficile (C. diff) infection can be diagnosed using two stool tests: nucleic acid amplification test (NAAT) and enzyme immunoassay (EIA) for C. diff toxins A and B, as recommended by the 2019 update of the WSES guidelines for management of Clostridioides (Clostridium) difficile infection in surgical patients 1. The diagnosis of C. diff infection should be based on clinical signs and symptoms in combination with laboratory tests, and stool testing should only be performed on diarrheal stools from at-risk patients with clinically significant diarrhea (≥ 3 loose stools in 24 h) with no obvious alternative explanation. The hypervirulent strain of C. diff, known as NAP1/BI/027, is hypervirulent for two main reasons:

  • It produces significantly higher amounts of toxins A and B due to mutations in the tcdC gene, which normally suppresses toxin production, as described in the 2013 guidelines for diagnosis and management of gastrointestinal complications in adult cancer patients 1.
  • This strain produces an additional binary toxin (CDT) that enhances its virulence by facilitating bacterial adherence to intestinal epithelium and contributing to more severe inflammation. These characteristics explain why infections with the hypervirulent strain typically result in more severe disease, higher rates of complications, increased mortality, and greater resistance to standard treatments, as highlighted in the 2019 update of the WSES guidelines 1. Some key points to consider when diagnosing C. diff infection include:
  • Clinical context such as a history of recent antibiotic administration and/or residence in hospital are useful in selecting patients for testing.
  • Other signs such as fever, abdominal pain, leukocytosis, in combination with other laboratory tests (e.g., creatinine and serum lactate) are useful for defining the severity of infection.
  • Nucleic acid amplification tests (NAAT) for C. difficile toxin genes appear to be sensitive and specific and may be used as a standard diagnostic test for CDI.
  • Glutamate dehydrogenase (GDH) screening tests for C. difficile are sensitive but do not differentiate between toxigenic and non-toxigenic strains, and may be used in association with toxin A/B enzyme immunoassays (EIA) testing, as recommended by the 2019 update of the WSES guidelines 1.

From the Research

C. diff Stool Tests

  • Two stool tests are commonly used to diagnose C. diff infection:
    • Stool toxin test, which detects the toxins produced by C. diff bacteria 2
    • Polymerase chain reaction (PCR) test, which detects the genetic material of C. diff bacteria 3

Hypervirulent Strain of C. diff

  • Two reasons why the hypervirulent strain of C. diff is hypervirulent are:
    • It produces more toxins than other strains, leading to more severe disease 2
    • It has a higher sporulation rate, making it more resistant to environmental stressors and antimicrobial agents 4

Note: The provided studies do not directly discuss the hypervirulent strain of C. diff, but they do provide information on the diagnosis and treatment of C. diff infection, as well as the characteristics of the bacteria.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Clostridium difficile infection: review.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 2019

Research

Fidaxomicin versus vancomycin for Clostridium difficile infection.

The New England journal of medicine, 2011

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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