According to results from an open-label randomized trial, extended-pulsed fidaxomicin, delivering 20 doses over a longer time period after initial daily dosing, appears superior to standard-dose vancomycin for sustained cure of Clostridium difficile infection in patients age 60 or older.The study results was published in the Lancet Infectious Diseases.

The narrow-spectrum macrolide antibiotic fidaxomicin (200 mg orally twice daily for 10 days) has been shown to be noninferior to standard vancomycin (125 mg orally four times daily for 10 days) for treating C. difficile infection, with reduced recurrence rates and improved sustained clinical cure rates.

In the EXTEND trial, Dr. Benoit Guery from the University of Lausanne, in Switzerland, and colleagues investigated whether extended-pulsed fidaxomicin improved sustained clinical-cure rates, compared with vancomycin, in a study of 364 hospitalized patients age 60 or older with C. difficile infection.

Significantly more patients in the extended-pulsed fidaxomicin group (70%) than in the vancomycin group (59%) had sustained clinical cure at 30 days after the end of treatment. More patients in the extended-pulsed fidaxomicin group also achieved the secondary efficacy endpoint of sustained clinical cure at days 40, 55, and 90.

In multivariate analysis, patients with severe C. difficile infection were less likely to achieve sustained clinical cure than were patients with nonsevere C. difficile infection. Thirty days after the end of treatment (day 55 for extended-pulsed fidaxomicin and day 40 for vancomycin), recurrence rates were significantly lower with extended-pulsed fidaxomicin (4%) than with vancomycin (17%).

Gut bacterial alpha diversity increased to a greater extent in extended-pulsed fidaxomicin-treated patients than in vancomycin-treated patients.Otherwise, the safety profiles for the two regimens appeared similar.

“Since the extended-pulsed regimen of fidaxomicin administers the same number of tablets as the standard regimen, the observed benefits are derived with no increase in treatment costs and with a similar positive safety profile to that of standard-regimen vancomycin and fidaxomicin,” the researchers note.

Dr. Dale N. Gerding from Edward Hines Jr. Veterans Affairs Hospital,said, Recurrence rates in the EXTEND study were lower for both vancomycin and fidaxomicin than they were in the earlier licensing trials;

Because, the difference in recurrence rate in EXTEND (-15.5%) is only slightly better than the difference in recurrence in the two prior trials, albeit with an older patient population that was randomized but treated open-label.

“This trial done open label also is not as convincing as it would be if done blinded, and fidaxomicin remains an expensive treatment for C. difficile infection,” he said.

“Pulsed dosing of either fidaxomicin or vancomycin is useful in reducing recurrence and should be employed more often in patients who are at high risk for recurrence, and this includes patients 65 or older,” Dr. Gerding concluded.