What is the clinical significance of a patient with a history of watery diarrhea, now resolved, who has tested positive for Clostridioides (C.) difficile toxin deoxyribonucleic acid (DNA) but negative for Clostridioides (C.) difficile toxin antigen?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: May 2, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

This patient likely has a C. difficile infection despite the negative toxin antigen test, and I recommend treating with oral vancomycin 125 mg four times daily for 10 days, as the positive DNA test indicates the presence of toxigenic C. difficile, and treatment is still warranted to prevent recurrence or complications, as suggested by the most recent guidelines 1. The discrepancy between positive DNA and negative toxin antigen can occur because the DNA test is more sensitive but less specific.

  • Alternatively, oral fidaxomicin 200 mg twice daily for 10 days could be used, which may reduce recurrence rates, as shown in previous studies 1.
  • During treatment, it is essential to avoid antimotility agents, continue probiotics if already taking them, and emphasize good hand hygiene with soap and water, as alcohol-based sanitizers are less effective against C. difficile spores.
  • Monitoring for recurrence of symptoms is crucial, as it occurs in about 20-30% of cases, and considering infectious disease consultation if symptoms recur after treatment is recommended, according to the guidelines 1. The recent guidelines from 2024 1 provide the most up-to-date recommendations for the management of C. difficile infection, and their suggestions should be prioritized in the treatment of this patient.

From the FDA Drug Label

Since clinical success at the end of treatment and mortality rates were similar across treatment arms The FDA drug label does not answer the question.

From the Research

Patient Profile

  • The patient had watery diarrhea 2 days ago but has had no symptoms since
  • Lab work shows C difficile toxin DNA positive and C difficile toxin antigen negative

Diagnosis and Treatment

  • According to 2, C difficile infection should be considered in patients with three or more episodes of unexplained, unformed stools in 24 hours
  • The patient's lab work indicates the presence of C difficile toxin DNA, but the toxin antigen is negative
  • 3 suggests that oral vancomycin or oral fidaxomicin is recommended for an initial episode of non-severe C difficile infection
  • 4 found that vancomycin had superior therapeutic effects compared to metronidazole in severe cases of C difficile infection
  • 5 and 6 compared the effectiveness of fidaxomicin, vancomycin, and metronidazole in treating C difficile infection, with mixed results

Treatment Options

  • Oral vancomycin is a recommended treatment option for C difficile infection, especially in severe cases 3, 4
  • Fidaxomicin is also a recommended treatment option, but its effectiveness compared to vancomycin and metronidazole is still being studied 5, 6
  • Metronidazole is no longer recommended as first-line therapy for adults with C difficile infection 2

Next Steps

  • The patient's doctor will need to determine the best course of treatment based on the patient's symptoms, lab results, and medical history
  • The doctor may consider prescribing oral vancomycin or fidaxomicin, and monitoring the patient's response to treatment 3, 2, 5, 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Clostridioides difficile Infection: Update on Management.

American family physician, 2020

Research

Update of treatment algorithms for Clostridium difficile infection.

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2018

Research

Oral vancomycin versus metronidazole for the treatment of Clostridioides difficile infection: Meta-analysis of randomized controlled trials.

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 2018

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.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.