What is fidaxomicin (Dificid)?

From the Guidelines

Fidaxomicin is an antibiotic medication primarily used to treat Clostridioides difficile (C. diff) infections, with a standard adult dosage of 200 mg taken orally twice daily for 10 days, as recommended by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) in their 2021 focused update guidelines 1.

Key Characteristics of Fidaxomicin

• Fidaxomicin works by inhibiting bacterial RNA synthesis, specifically targeting C. diff while preserving much of the normal gut microbiome.
• It is minimally absorbed systemically, meaning it stays primarily in the gastrointestinal tract where the infection is located, which helps reduce systemic side effects.
• Common side effects may include nausea, vomiting, abdominal pain, and gastrointestinal bleeding.

Treatment Guidelines

• For initial CDI episodes, fidaxomicin is a preferred treatment option, given its lower recurrence rate compared to vancomycin 1.
• For recurrent CDI, fidaxomicin is also preferred, with an extended-pulsed regimen showing improved sustained responses and lower recurrence rates compared to vancomycin 1.
• Fidaxomicin may be used for severe cases or recurrent infections, but its higher cost compared to other antibiotics should be considered.

Comparison to Other Treatments

• Fidaxomicin has been shown to have a lower recurrence rate compared to vancomycin, making it a valuable treatment option for C. diff infections 1.
• Vancomycin is still a recommended treatment option, particularly for fulminant CDI, but fidaxomicin is preferred for its lower recurrence rate and targeted action.

Clinical Considerations

• Fidaxomicin should be used with caution in patients with a history of congestive heart failure, as it may increase the risk of adverse events 1.
• The use of fidaxomicin in combination with other treatments, such as bezlotoxumab, may be considered for patients with recurrent CDI or other risk factors for recurrence.

From the FDA Drug Label

DIFICID (fidaxomicin) is a macrolide antibacterial drug for oral administration Its CAS chemical name is Oxacyclooctadeca-3,5,9,13,15-pentaen-2-one, 3-[[[6-deoxy-4-O-(3,5-dichloro-2-ethyl-4,6-dihydroxybenzoyl)-2-O-methyl-β-D-mannopyranosyl]oxy]methyl]-12-[[6-deoxy-5-C-methyl-4-O-(2-methyl-1-oxopropyl)-β-D-lyxo-hexopyranosyl]oxy]-11-ethyl-8-hydroxy-18-[(1R)-1-hydroxyethyl]-9,13,15-trimethyl-, (3E,5E,8S,9E,11S,12R,13E,15E,18S)-

Fidaxomicin (Dificid) is a macrolide antibacterial drug used for oral administration. It is specifically used to treat Clostridioides difficile-associated diarrhea (CDAD). The drug works by inhibiting RNA synthesis by binding to RNA polymerases, which are essential for the growth and survival of C. difficile bacteria 2.

From the Research

Definition and Mechanism of Fidaxomicin

• Fidaxomicin is a novel macrocyclic antibiotic used for the treatment of Clostridium difficile infection (CDI) 3, 4, 5.
• It has a narrow spectrum of activity against gram-positive anaerobes and is bactericidal against C. difficile, with minimal activity against Bacteroides species 3.
• Fidaxomicin works by inhibiting RNA polymerase, a mechanism distinct from rifamycins, and has been shown to be effective in treating CDI with a lower rate of recurrence compared to vancomycin 4, 5.

Clinical Efficacy and Safety

• Fidaxomicin has been shown to be noninferior to vancomycin in the management of mild-to-moderately severe CDI, with a similar adverse-effect profile 3, 4.
• Clinical trials have demonstrated that fidaxomicin is associated with a significantly lower rate of recurrence of C. difficile infection, particularly in patients with non-North American Pulsed Field type 1 strains 4.
• Real-world studies have also shown that fidaxomicin is associated with a lower risk of treatment failure, including clinical failure, 30-day relapse, or CDI-related death 6.

Dosage and Administration

• The recommended dosage for treatment of CDI is fidaxomicin 200 mg orally twice daily for 10 days 3, 5.
• Fidaxomicin should be considered for patients who previously received treatment with metronidazole or vancomycin for CDI and who are diagnosed with recurrent CDI in which a non-NAP1/BI/027 strain is isolated 3.

Potential Role in Prophylaxis

• Fidaxomicin's potential role as a prophylactic agent against C. difficile infection is being studied, with its properties suggesting it may be effective in reducing recurrent CDAD 7.
• The use of fidaxomicin as a prophylactic agent, particularly in high-risk patients, may be a promising area of research 7.