Fidaxomicin Vs. Vancomycin: What's More Effective for Treating C difficile?

Clostridium difficile (C. difficile) is one of the biggest healthcare-associated infections faced by health care workers everywhere; to make matters worse, severity and incidence of the disease have increased significantly in past years.

C. difficile was once considered a serious health problem experienced mainly by older individuals placed on antibiotics during a hospital or nursing home stay, however, recent research now shows a rising incidence of C. difficile infection among a younger and healthier population.

A 2015 CDC study found that C. difficile was behind almost a half-million infections among patients in the US over just 1-year-old; of that half-million, approximately 15,000 individuals died as a result of their C. difficile infections. Over 80% of that number were Americans 65 years of age or older. Furthermore, between 20—30% of patients who experience an initial episode of C. difficile infection either relapse or experience a recurrent infection.

A recent study published in The Lancet Infectious Diseases compared the effectiveness of a novel fidaxomicin antibiotic therapy with vancomycin for the treatment of C. difficile.

The study, referred to as EXTEND, was a randomized, open-label study conducted in hospitals across 22 European countries. The primary objective of EXTEND was to evaluate whether extended-pulsed fidaxomicin (EPFX) was superior to standard vancomycin therapy for sustained clinical cure of C. difficile 30 days after end of treatment

They describe a dosing regimen for fidaxomicin where the standard 200 mg, 20-dose, 10-day regimen is lengthened by using a 200 mg twice daily dose for the first 5 days, followed by 200 mg every other day for another 20 days. The comparator regimen used was 125 mg of vancomycin given 4 times daily over a 10-day period.

From November 6, 2014, to May 5, 2016, 364 patients were enrolled in the study. Each was randomly assigned to either receive EPFX or vancomycin, where 362 patients were given at least 1 dose of the study medication. From the modified full analysis set, 124 of 177 patients received extended-pulsed fidaxomicin and had a sustained cure, 30-days after the end of treatment. This is compared with only 106 of 179 of patients that were receiving vancomycin.

When asked whether the findings mean that vancomycin should no longer be used to treat initial cases of C. difficile in favor of EPFX or if EPFX should only be used in relapse/recurrent infections, lead author Benoit Guery, MD, said “There’s no easy answer to this one. If you think only with medical issues, the answer is clearly yes, narrow-spectrum, same response but a decreased number of relapse. But the cost can’t be ignored so it’s really difficult to support a complete replacement. The best way to deal with that is to replace vancomycin with EPFX in patients at risk of recurrence. Even with that, it is not easy if you take the ECCMID criteria with, again, a limit age at 65 because a large number of patients would require EPFX.”

Dr. Guery believes that, due to the expense of EPFX, it will not be a viable treatment option for C. difficile patients in developing countries. Although, when asked what changes to C. difficile treatment he anticipates in light of the EXTEND study findings, he stated that, “When physicians choose to administer fidaxomicin they should use the EPFX protocol to optimize treatment.”

It should be noted that the incidence of adverse outcomes did not differ between EPFX and vancomycin treatment arms. However, an investigator did consider 1 death in the vancomycin arm to be related to the study drug.

Data from the EXTEND study showed that EPFX provided a superior rate of sustained clinical cure at 30 days after treatment compared to vancomycin. After 40 days, recurrence rates were found to be almost 10 times lower in the patients treated with EPFX than those treated with standard vancomycin.