Does a patient with a stool test positive for Clostridioides difficile (C. diff) toxin require treatment?

From the Guidelines

Yes, a patient with a positive stool C. difficile toxin test requires treatment. The most recent and highest quality study, published in 2020 1, recommends antibiotic therapy for symptomatic cases with a positive stool C. difficile test.

Treatment Options

• For mild to moderate cases, oral vancomycin 125 mg four times daily for 10 days is the first-line therapy, as it has been shown to be effective in treating C. difficile infection 1.
• Alternatively, fidaxomicin 200 mg twice daily for 10 days can be used, as it has been found to be a valid alternative to vancomycin in patients with CDI 1.
• For severe cases, oral vancomycin 125 mg four times daily for 10 days is recommended, with consideration for higher doses (up to 500 mg four times daily) in severe complicated cases 1.
• For fulminant cases with hypotension or shock, a combination of intravenous metronidazole 500 mg every 8 hours plus oral vancomycin 500 mg four times daily (with rectal vancomycin if ileus is present) is recommended 1.

Additional Considerations

• Treatment is necessary because C. difficile infection can cause severe diarrhea, colitis, and potentially life-threatening complications like toxic megacolon or perforation.
• The toxins produced by C. difficile damage the intestinal lining and cause inflammation.
• Additionally, patients should discontinue unnecessary antibiotics if possible, maintain hydration, avoid anti-motility agents, and implement contact precautions to prevent transmission.
• Approximately 20-30% of patients may experience recurrence after initial treatment, which may require extended or alternative treatment regimens.

Special Cases

• Fecal microbiota transplantation (FMT) is an effective option for patients with multiple CDI recurrences who have failed appropriate antibiotic treatments 1.
• Coadjuvant treatment with monoclonal antibodies (bezlotoxumab) may prevent recurrences of CDI, particularly in patients with CDI due to the 027 epidemic strain, in immunocompromised patients and in patients with severe CDI 1.

From the FDA Drug Label

In two randomized, double-blinded trials, a non-inferiority design was utilized to demonstrate the efficacy of DIFICID (200 mg tablets twice daily for 10 days) compared to vancomycin (125 mg four times daily for 10 days) in adults with CDAD Enrolled patients were 18 years of age or older and received no more than 24 hours of pretreatment with vancomycin or metronidazole. CDAD was defined by >3 unformed bowel movements (or >200 mL of unformed stool for subjects having rectal collection devices) in the 24 hours before randomization, and presence of either C. difficile toxin A or B in the stool within 48 hours of randomization

Treatment is required for a patient with a stool test positive for Clostridioides difficile (C. diff) toxin, as the presence of the toxin is used to define CDAD in the clinical trials, and treatment with fidaxomicin or vancomycin is shown to be effective in resolving diarrhea and preventing recurrence of CDAD 2, 3.

• Key points:
  • CDAD is defined by the presence of C. difficile toxin A or B in the stool
  • Treatment with fidaxomicin or vancomycin is effective in resolving diarrhea and preventing recurrence of CDAD
  • The presence of the toxin is a key factor in determining the need for treatment

From the Research

Treatment of Clostridioides difficile Infection

• A patient with a stool test positive for Clostridioides difficile (C. diff) toxin generally requires treatment, as C. difficile infection is a serious diarrheal illness associated with substantial morbidity and mortality 4.
• The treatment approach may vary depending on the severity of the infection and the patient's medical history, but oral vancomycin or fidaxomicin are commonly used as first-line therapies 5, 6, 7.
• For patients with recurrent C. difficile infection, fecal microbiota transplantation (FMT) is a highly efficacious treatment option, with a success rate of over 85% 6, 7, 8.
• In some cases, a vancomycin taper and pulse or fidaxomicin may be used to manage recurrent infection, and intravenous bezlotoxumab (a monoclonal antibody against the toxin B) may be recommended to reduce recurrence rates 6.

Treatment Options

• Fidaxomicin has been shown to be noninferior to vancomycin in terms of clinical cure rates, and is associated with a significantly lower rate of recurrence of C. difficile infection 4.
• Vancomycin is also an effective treatment option, and may be used in combination with FMT for patients with multiple recurrent C. difficile infection 5, 7.
• Metronidazole is no longer recommended as first-line therapy due to its lower efficacy and higher risk of recurrence 5, 7.
• Newer antibiotics, such as cadazolid and ridinilazole, are being developed and tested as potential treatment options for C. difficile infection 7.

Special Considerations

• Patients with inflammatory bowel disease (IBD) are at higher risk for C. difficile infection, and may require a different treatment approach 5.
• For patients with IBD, oral vancomycin or fidaxomicin are preferred agents for nonfulminant disease, and FMT should be considered for patients with recurrent C. difficile infection 5.
• Escalation of immunosuppression with appropriate antimicrobial treatment of C. difficile may be necessary for patients with worsening IBD symptoms 5.