What treatment to give in a patient setting if a patient tests positive for Clostridioides difficile (C. diff)?

From the Guidelines

For a patient with confirmed Clostridioides difficile (C. diff) infection, the recommended treatment is fidaxomicin 200 mg twice daily for 10 days or vancomycin 125 mg four times daily for 10 days for initial non-severe cases. The choice of treatment depends on the severity and recurrence status of the infection. According to the 2021 clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) 1, for initial CDI episodes, fidaxomicin and vancomycin are the preferred and alternative treatments, respectively.

For severe cases, the same regimens are used, though vancomycin is often preferred.

• Key considerations for treatment include:
  • Severity of the infection
  • Recurrence status
  • Presence of complications such as ileus or megacolon
  • Patient's overall health status and medical history

For fulminant C. diff (hypotension, shock, ileus), vancomycin 500 mg four times daily orally or via nasogastric tube, plus intravenous metronidazole 500 mg every 8 hours if ileus is present, is recommended 1. For recurrent infections, extended vancomycin tapers or fidaxomicin may be used. Metronidazole (500 mg three times daily for 10 days) is now considered a second-line agent due to increasing resistance.

Additionally, implementing contact precautions with gloves and gowns, placing the patient in isolation, practicing proper hand hygiene with soap and water, and discontinuing unnecessary antibiotics if possible are crucial 1. These treatments target the toxin-producing bacteria while minimizing disruption to the normal gut microbiome. It is essential to note that the treatment approach may vary depending on the specific clinical scenario and patient factors, and fidaxomicin is suggested over vancomycin for patients with recurrent CDI episodes 1.

From the FDA Drug Label

14 CLINICAL STUDIES 14. 1 Diarrhea Associated with Clostridium difficile In two trials, Vancomycin Hydrochloride Capsules 125 mg orally four times daily for 10 days was evaluated in 266 adult subjects with C. difficile-associated diarrhea (CDAD)

1 INDICATIONS AND USAGE 1.1 Clostridioides difficile-Associated Diarrhea DIFICID® is indicated in adult and pediatric patients aged 6 months and older for the treatment of C. difficile-associated diarrhea (CDAD).

Treatment for C. difficile-associated diarrhea (CDAD):

• Vancomycin Hydrochloride Capsules 125 mg orally four times daily for 10 days 2
• Fidaxomicin (DIFICID) for the treatment of CDAD in adult and pediatric patients aged 6 months and older 3

From the Research

Treatment Options for Clostridioides difficile Infection

• Fidaxomicin, vancomycin, and metronidazole are commonly used antibiotics for the treatment of Clostridioides difficile infection (CDI) 4.
• Fidaxomicin has been shown to be superior to metronidazole, vancomycin, or their combination for a sustained clinical response and in the prevention of recurrent CDI in the initial episode, first recurrence, and non-severe cases 5.
• However, fidaxomicin was found to be inferior to metronidazole for recurrent CDI (rCDI) in one study 6.
• Vancomycin and fidaxomicin have been associated with higher odds of prolonged hospitalization, and fidaxomicin has been linked to an increased risk of suffering another episode of CDI 6.

Comparison of Treatment Outcomes

• A systematic review and meta-analysis found that fidaxomicin and vancomycin/metronidazole regimens did not have significant differences in terms of treatment outcomes, such as clinical cure, sustained cure, recurrence, and all-cause mortality 7.
• However, fidaxomicin was associated with a significantly higher risk of treatment failure in CDI patients 7.
• Another study found that fidaxomicin had a higher sustained clinical cure rate at 30- and 60-days follow-up compared to vancomycin 8.

Economic Outcomes

• Fidaxomicin has been reported to be cost-effective in many economic analyses, particularly among high-risk subpopulations such as patients receiving concomitant antibiotics, and patients with cancer or renal impairment 8.
• The higher acquisition cost of fidaxomicin is often offset by reduced recurrence and hospital readmission costs 8.