Purpose: The pharmacology, clinical efficacy, safety, dosage and administration, and place in therapy of fidaxomicin for the treatment of Clostridium difficile infection (CDI) are reviewed.
Summary: Fidaxomicin, a macrocyclic antibiotic, has a narrow spectrum of activity against gram-positive anaerobes and is bactericidal against C. difficile. It has no activity against gram-negative bacteria. Fidaxomicin has minimal activity against Bacteroides species, which may be advantageous in maintaining colonization resistance and protecting the gastrointestinal tract from colonization by C. difficile. The minimum inhibitory concentration for 90% of organisms for fidaxomicin against C. difficile ranged from 0.0078 to 2 μg/mL in in vitro studies. After oral administration, fecal concentrations are detected and are directly proportional to the dose administered. Fidaxomicin resistance in vivo has not been reported. In clinical trials, fidaxomicin has been shown to be noninferior to vancomycin in the management of mild-to-moderately severe CDI. The adverse-effect profile of fidaxomicin is comparable to that of vancomycin. The recommended dosage for treatment of CDI is fidaxomicin 200 mg orally twice daily for 10 days. 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. At institutions where strain typing is not available, fidaxomicin may be considered in patients with recurrent CDI who have not responded to treatment with the regimen used for the first episode of CDI.
Conclusion: Fidaxomicin is a well-tolerated agent for the treatment of CDI and has been shown to be noninferior to vancomycin in the management of mild-to-moderately severe CDI.