Why is oral vancomycin (Vancomycin) not used as the first choice to treat Clostridioides difficile (C. diff) infection?

From the Guidelines

Oral vancomycin should not be used as the first choice to treat Clostridioides difficile (C. difficile) infection due to the availability of more effective and safer alternatives, such as fidaxomicin, which has been shown to have beneficial effects and safety, as suggested by the 2021 clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) 1.

Rationale for Not Using Oral Vancomycin as First Choice

• The guideline recommends using fidaxomicin rather than vancomycin for patients with an initial C. difficile infection episode, placing a high value on the beneficial effects and safety of fidaxomicin 1.
• Vancomycin remains an acceptable alternative, but its use is conditional and depends on available resources, suggesting that fidaxomicin is the preferred option when possible 1.
• For patients with recurrent C. difficile episodes, fidaxomicin is also suggested over vancomycin, although vancomycin in a tapered and pulsed regimen is an acceptable alternative 1.

Considerations for Treatment

• The choice of treatment should consider the severity of the infection, the patient's medical history, and the availability of resources.
• Fidaxomicin has been shown to have a moderate certainty of evidence for its beneficial effects, making it a preferred option for initial treatment 1.
• Vancomycin is still a viable option for severe cases or when fidaxomicin is not available, but its use should be guided by clinical judgment and antimicrobial stewardship principles.

Clinical Implications

• The use of fidaxomicin as the first choice for treating C. difficile infection can help minimize the risk of developing vancomycin-resistant enterococci (VRE) and preserve the effectiveness of vancomycin for more serious infections.
• Clinicians should consider the latest guidelines and evidence when making treatment decisions for C. difficile infection, prioritizing the use of fidaxomicin over vancomycin when possible 1.

From the FDA Drug Label

Vancomycin hydrochloride capsules must be given orally for treatment of staphylococcal enterocolitis and C. difficile-associated diarrhea. Orally administered vancomycin hydrochloride capsules are not effective for other types of infections. Clinically significant serum concentrations have been reported in some patients who have taken multiple oral doses of vancomycin hydrochloride capsules for active C. difficile-associated diarrhea. Nephrotoxicity has occurred following oral vancomycin hydrochloride capsule therapy and can occur either during or after completion of therapy. The risk is increased in geriatric patients. Ototoxicity has occurred in patients receiving vancomycin hydrochloride capsules. Severe Dermatologic Reactions: Discontinue vancomycin hydrochloride capsules at the first appearance of skin rashes, mucosal lesions, or blisters.

The FDA drug label does support the use of oral vancomycin as a treatment for C. difficile-associated diarrhea. However, it also highlights several warnings and precautions, including the risk of nephrotoxicity, ototoxicity, and severe dermatologic reactions. The label also notes that clinically significant serum concentrations can occur in some patients, which may require monitoring of serum concentrations. Given these potential risks, it is possible that oral vancomycin may not have been chosen as the first-line treatment due to concerns about its safety profile 2.

From the Research

Reasons for Not Using Oral Vancomycin as 1st Choice

• Oral vancomycin is a first-line treatment for an initial episode of Clostridioides difficile infection, but its efficacy compared to other treatments is still being studied 3.
• The use of oral vancomycin may not be sufficient for severe or complicated cases of C. difficile infection, and other treatments such as fecal microbiota transplantation (FMT) may be more effective 4, 5, 6.
• FMT has been shown to be superior to vancomycin for the treatment of recurrent C. difficile infection, with higher rates of clinical resolution and negative results from polymerase chain reaction tests for C. difficile toxin 5, 6.
• Other treatments, such as fidaxomicin, may also be effective for the treatment of C. difficile infection, particularly in patients with inflammatory bowel disease 7.
• The choice of treatment for C. difficile infection may depend on the severity of the infection, the patient's underlying medical conditions, and the presence of recurrent infection.

Comparison of Treatments

• A network meta-analysis found that FMT was the most efficacious treatment for recurrent C. difficile infection, compared to vancomycin, fidaxomicin, and other treatments 5.
• A randomized trial found that FMT was superior to fidaxomicin and vancomycin for the treatment of recurrent C. difficile infection, with higher rates of clinical resolution and negative results from polymerase chain reaction tests for C. difficile toxin 6.
• A retrospective study found that fidaxomicin was effective for the treatment of C. difficile infection in patients with inflammatory bowel disease, but that FMT may be an effective therapy for patients who do not respond to fidaxomicin 7.

Considerations for Treatment Choice

• The choice of treatment for C. difficile infection should be based on the individual patient's needs and medical history 3, 4, 5, 6, 7.
• Patients with severe or complicated C. difficile infection may require more aggressive treatment, such as FMT or a combination of antibiotics and FMT 4, 5, 6.
• Patients with recurrent C. difficile infection may benefit from FMT or other treatments that target the underlying causes of the infection 5, 6.