"Fidaxomicin versus Vancomycin for Clostridium difficile Infection". The New England Journal of Medicine. 2011. 364:422-431. PubMed • Full text • PDF
Contents
1Clinical Question
2Bottom Line
3Major Points
4Guidelines
5Design
6Population
6.1Inclusion Criteria
6.2Exclusion Criteria
6.3Baseline Characteristics
7Interventions
8Outcomes
8.1Primary Outcomes
8.2Secondary Outcomes
9Criticisms
10Funding
11Further Reading
Clinical Question
In adults with Clostridium difficile infection, how does fidaxomicin compare to vancomycin in terms of efficacy and safety?
Bottom Line
Fidaxomicin treatment for C. difficile infection was noninferior to vancomycin for clinical cure rates and was associated with significantly lower rates of recurrence, especially in patients infected with non-North American Pulsed Field type 1 strains of C. difficile.
Major Points
The emergence of hypervirulent strains of C. difficile (NAP1/BI/027) has increased the morbidity and mortality associated with C. difficile infection. Fidaxomicin is a macrocyclic antibiotic that has shown promise in targeting C. difficile with minimal systemic absorption and has a spectrum of activity that spares much of the natural gut flora. In this phase 3 clinical trial, fidaxomicin was found to be noninferior to vancomycin in terms of clinical cure rates and had significantly lower recurrence rates.
Guidelines
As of the knowledge cutoff date, no specific guidelines are provided pertaining to the trial results. Typically, clinical practice guidelines are periodically updated to reflect new evidence, and fidaxomicin may be included based on these results.
Design
- Multicenter, prospective, double-blind, randomized, parallel-group trial
- N=629 patients with acute C. difficile infection
- Fidaxomicin (200 mg twice daily) or vancomycin (125 mg four times daily)
- Primary endpoint: Clinical cure
- Secondary endpoints: Recurrence of C. difficile infection and global cure
- Setting: 52 sites in the United States and 15 sites in Canada
- Enrollment: May 9, 2006, and August 21, 2008
Population
- Adults (≥16 years) with acute symptoms of C. difficile infection and a positive stool toxin test
Inclusion Criteria
- ≥3 unformed bowel movements in the 24-hour period before randomization
- Positive C. difficile toxin A, B, or both in a stool specimen within 48 hours before randomization
Exclusion Criteria
- Life-threatening or fulminant C. difficile infection, toxic megacolon, previous exposure to fidaxomicin, history of ulcerative colitis or Crohn's disease, or more than one occurrence of C. difficile infection within 3 months before the study
Baseline Characteristics
- Similar across treatment groups
Interventions
- Double-blind assignment of either fidaxomicin 200 mg BID with placebo doses or vancomycin 125 mg QID for 10 days
Outcomes
Primary Outcomes
- Clinical cure rate post-treatment (fidaxomicin: 88.2% in modified intention-to-treat analysis and 92.1% in per-protocol analysis; vancomycin: 85.8% and 89.8%, respectively)
Secondary Outcomes
- Recurrence rate (fidaxomicin: 15.4% in modified intention-to-treat analysis; vancomycin: 25.3%)
- Global cure rate (fidaxomicin: 74.6% in modified intention-to-treat analysis; vancomycin: 64.1%)
Criticisms
- Although the non-inferiority design showed fidaxomicin was at least as effective as vancomycin, questions remain regarding long-term outcomes beyond the scope of the study.
- Cost-effectiveness of fidaxomicin in comparison to vancomycin was not addressed.
Funding
- Funded by Optimer Pharmaceuticals; ClinicalTrials.gov number, NCT00314951.
Further Reading
- Full text of the study can be found at The New England Journal of Medicine website.