This double-blind, randomised controlled, non-inferiority trial compared the efficacy and safety of oral fidaxomicin and oral vancomycin for the treatment of patients with Clostridium difficile (C difficile) infection in 45 sites across Europe, Canada, and the USA.

Eligible patients, aged 16 years or older with acute, toxin-positive C difficile infection were randomised to fidaxomicin (n=270; 200 mg every 12 h) or vancomycin (n=265; 125 mg every 6 h) for 10 days. Non-inferiority was prespecified with a margin of 10%. Modified intention-to-treat (mITT)  and per-protocol populations were analysed.

The primary endpoint was clinical cure, defined as resolution of diarrhoea (three or fewer unformed bowel movements per day for two consecutive days) and no further need for treatment. This was met in 198 (91.7%) of 216 patients in the per-protocol population given fidaxomicin compared with 213 (90.6%) of 235 given vancomycin, meeting the criterion for non-inferiority (one-sided 97.5% CI −4.3%).

Non-inferiority was also demonstrated for the primary endpoint in the mITT population, with 221 (87.7%) of 252 patients given fidaxomicin and 223 (86.8%) of 257 given vancomycin cured (one-sided 97•5% CI −4•9%).

Adverse effects were reported in be similar in both groups and consisted of gastrointestinal symptoms (ie, nausea, vomiting, diarrhoea, and abdominal pain). A total of 20 (7.6%) of 264 patients given at least one dose of fidaxomicin and 17 (6.5%) of 260 given vancomycin died.

The authors conclude that fidaxomicin was non-inferior to vancomycin for clinical cure rate and could be an alternative treatment for infection with C difficile, with similar efficacy and safety to vancomycin.
An accompanying editorial discusses the findings of this study.

[Editors note: fidaxomicin (Dificlir™) is the first in a new class of antibiotics called macrocyclics and has recently been approved in the EU for the treatment of adults with Clostridium difficile-associated diarrhoea.]