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Fidaxomicin

In Clostridium difficile Infection

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Abstract

Fidaxomicin is a first-in-class macrocyclic antibacterial that primarily demonstrates activity against species of clostridia, predominantly Clostridium difficile, while having limited or no activity against normal faecal microflora. Fidaxomicin is minimally absorbed following oral administration and is excreted almost solely in the faeces.

Fidaxomicin displayed a high level of antibacterial activity against C. difficile in vitro, with a minimum inhibitory concentration required to inhibit 90% of C. difficile strains of 0.125–0.5 μg/mL, and was ≈2 - to 8-fold more active than vancomycin or metronidazole. Fidaxomicin demonstrated a prolonged postantibiotic effect against C. difficile relative to vancomycin and metronidazole.

In two randomized, double-blind, phase III trials, oral fidaxomicin 200 mg every 12 hours for 10 days was no less effective than oral vancomycin 125 mg every 6 hours for 10 days in the treatment of C. difficile infection, based on non-inferiority analyses of clinical cure rates (primary endpoint).

Fidaxomicin therapy was associated with a significantly lower rate of recurrence, as well as a significantly higher rate of global cure (i.e. sustained clinical response; resolution of diarrhoea without recurrence) compared with vancomycin therapy in the two clinical trials.

Fidaxomicin was generally well tolerated in patients with C. difficile infection, with a tolerability profile generally similar to that of vancomycin.

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Acknowledgements and Disclosures

The manuscript was reviewed by: T.J. Louie, Departments of Medicine and Microbiology and Infectious Diseases, University of Calgary, Calgary, AB, Canada;J.M. Blondeau, Department of Clinical Microbiology, Royal University Hospital, Saskatoon, SK, Canada.

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.

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    Sean T. Duggan

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Duggan, S.T. Fidaxomicin. Drugs 71, 2445–2456 (2011). https://doi.org/10.2165/11208220-000000000-00000

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