New Drug Shows Promise in Treating C. difficile Recurrence

February 8, 2011

The investigational antibiotic fidaxomicin was found to significantly cut the rate of Clostridium difficile recurrence compared to treatment with vancomycin.

The investigational antibiotic fidaxomicin was found to significantly cut the rate of Clostridium difficile recurrence compared to treatment with vancomycin, according to findings published in the New England Journal of Medicine.

C. difficile infection is a serious diarrheal illness associated with substantial morbidity and mortality. Although patients generally respond to oral vancomycin or metronidazole, the rate of recurrence is high. In this phase 3 clinical trial, researchers from the University of Calgary colleagues compared the efficacy and safety of fidaxomicin with those of vancomycin in treating C. difficile infection.

Nearly 700 C. difficile patients in the United States and Canada with acute symptoms of C. difficile infection and a positive result on a stool toxin test were recruited for the study, and were randomly assigned to receive fidaxomicin (200 mg twice daily) or vancomycin (125 mg four times daily) orally for 10 days. The primary end point was clinical cure, defined as “resolution of symptoms and no need for further therapy for C. difficile infection as of the second day after the end of the course of therapy.” The secondary end points were recurrence of C. difficile infection (diarrhea and a positive result on a stool toxin test within 4 weeks after treatment) and global cure (no recurrence).

Of the 629 eligible subjects, 548 (87.1%) could be evaluated for the per-protocol analysis.

Lead author Thomas J. Louie, MD, and colleagues found the rates of clinical cure with fidaxomicin were noninferior to those with vancomycin in both the modified intention-to-treat analysis (88.2% with fidaxomicin and 85.8% with vancomycin) and the per-protocol analysis (92.1% and 89.8%, respectively) groups. Significantly fewer patients in the fidaxomicin group than in the vancomycin group had a recurrence of the infection, in both the modified intention-to-treat analysis (15.4% vs. 25.3%, P=0.005) and the per-protocol analysis (13.3% vs. 24.0%, P=0.004) groups. The lower rate of recurrence was seen in patients with non—North American Pulsed Field type 1 strains, and the adverse-event profile was similar for the two therapies, according to the authors.

They concluded that “the rates of clinical cure after treatment with fidaxomicin were noninferior to those after treatment with vancomycin,” and that “Fidaxomicin was associated with a significantly lower rate of recurrence of C. difficile infection associated with non—North American Pulsed Field type 1 strains.”

The study is funded by Optimer Pharmaceuticals.