Fidaxomycin is superior to vancomycin in the treatment of relapses of gastrointestinal tract infections caused by Clostridium difficile - such results from a blinded randomized controlled trial were presented in September 2010 at of the 50th Interdisciplinary Conference on Antimicrobial Drugs and Chemotherapy (50th Interscience Conference on Antimicrobial Agents and Chemotherapy - ICAAC) in Boston (Massachusetts, USA).

For the past 20 years, vancomycin has been the best drug to treat C. difficile. The problem was only a relatively high relapse rate in debilitated patients, which reached 30%. We now know that relapse can be prevented after using vancomycin using fidaxomine. Results from Phase III clinical trials show that fidaxomycin, used as the drug of choice, was superior to vancomycin in the treatment of C. diarrhea associated with difficult.

Fidaxomycin is the first representative of the class of macrocyclic antibiotics developed by Optimer Pharmaceuticals. This drug has a narrow spectrum of activity, acts only on pathogenic bacteria, has a powerful bactericidal activity against C. difficile and does not affect the normal intestinal microflora. Unlike fidaxomycin, two other drugs (vancomycin and metronidazole) are approved for use in this indication and, therefore, are often used to treat C. diarrhea associated with difficult inhibits the growth of normal endogenous microflora.

A nesting study (or a case-control study in a cohort) presented to the ICAAC was conducted in a predefined population of 178 patients with C. diarrhea associated with difficult in which the first relapse occurred within 90 days of the initial episode of C. difficile infection. These 178 patients participated in 2 randomized phase III trials which were carried out in 1164 patients suffering from infection caused by C. difficile. In the two phase III trials, fidaxomycin met the "no worse" criterion than vancomycin administered orally to prevent relapse within 30 days of the end of the 10-day treatment.

Relapse was defined as the presence of 3 or more episodes of unformed stool within 24 hours before randomization and the presence of C. difficile toxins A or B in feces within 48 hours following randomization. Patients were randomized to receive fidaxomycin or vancomycin. Fidaxomycin was prescribed at a dose of 200 mg twice a day by mouth, vancomycin - 125 mg 4 times a day by mouth for 10 days. According to phase III studies, over 90% of patients in both groups responded to the initial treatment.

In the nesting study, 55% of the patients were female, 53% were in the hospital and the average age of the patients was 63 years. Among 122 patients to be assessed, fidaxomycin was statistically significantly superior to vancomycin in the primary endpoint - the occurrence of a secondary relapse within 28 days (19.7% vs 35, 5%, p = 0.045). Fidaxomycin was also found to be statistically significantly better than vancomycin in preventing a second relapse within 14 days (7.6% vs 27.4%, p = 0.003).

Older age was a risk factor for relapse C. difficile - in this study, the risk of relapse in patients aged 75 and over was 2.7 times higher than in patients aged 18 to 54.

According to the researchers, the most likely explanation for the superior clinical efficacy of fidaxomycin in these studies was the fact that the normal intestinal microflora protects against the appearance of C. difficile -d associated diarrhea in patients receiving the new drug, while persistent C. difficile spores in the intestines remain in patients receiving vancomycin.

According to the researchers, additional studies are needed to determine the presumed relationship between the various effects of vancomycin and fidaxomycin on the bacterial flora of the intestine and the frequency of relapses, and to determine whether these various effects can actually cause different clinical effects when using the compared antibacterial drugs.