Extended-pulsed fidaxomicin proved superior to standard vancomycin therapy for sustained clinical cure after 30 days.
Benoit Guery, MD
Clostridium difficile (C. difficile) is presently one of the largest drug-resistant threats to our population according to the Centers for Disease Control and Prevention (CDC), and the severity and incidence have risen significantly in recent 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, but 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. Of that half-million, approximately 15,000 people died as a result of their C. difficile infections. Over 80% of that number were Americans 65 years of age or older.
Between 20—30% of patients who experience an initial episode of C. difficile infection, either relapse or experience a recurrent infection. According to research published in The Lancet Infectious Diseases (EXTEND Study), researchers compared the effectiveness of a novel fidaxomicin antibiotic therapy against vancomycin.
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 Nov 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 should EPFX only be used in relapse/recurrent infections, lead author Benoit Guery, MD, said that, “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 decreased number of relapse. But the cost can’t be ignored so really difficult to support a complete replacement. The best way to deal with that is to replace vanco by 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.”
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, Guery stated that, “When physicians choose to administer fidaxomicin they should use the EPFX protocol to optimize treatment.”The incidence of adverse outcomes did not differ between EPFX and vancomycin treatment arms. 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.