Fidaxomicin has a structure similar to the macrolides; however, it has a unique mechanism of action. It acts on the sigma subunit of RNA polymerase, thereby disrupting bacterial transcription, terminating protein synthesis, and resulting in cell death in susceptible organisms.
Fidaxomicin has a very narrow spectrum of activity limited to (gram-positive) aerobes and anaerobes.
It is used primarily for its bactericidal activity against Clostridium difficile because following oral administration, fidaxomicin has minimal systemic absorption and primarily remains within the gastrointestinal tract. This is ideal for the treatment of C. difficile infection, which occurs in the gut.
This characteristic also likely contributes to the low rate of adverse effects. Due to the unique target site, cross-resistance with other antibiotic classes has not been documented.
ADVERSE EFFECTS
- The most common adverse effects of fidaxomicin include nausea, vomiting, and abdominal pain.
- Anemia and neutropenia have been observed infrequently.
- Hypersensitivity reactions including angioedema, dyspnea, and pruritus have occurred.
- Fidaxomicin should be used with caution in patients with a macrolide allergy, as they may be at increased risk for hypersensitivity.