Investigational Fidaxomicin Tops Vancomycin for Recurrent C. Difficile Infection

BOSTON – Fidaxomicin is superior to vancomycin for the treatment of recurrent Clostridium difficile infection, investigators reported Sept. 14 at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

In a randomized controlled trial comparing the efficacy of fidaxomicin, a narrow-spectrum macrocyclic antibiotic, and vancomycin in 128 patients with recurrent Clostridium difficile infection (CDI) within 90 days of treatment for the initial CDI episode, fidaxomicin was associated with a 45% reduction in a subsequent CDI recurrence relative to vancomycin. Specifically, 13 of 66 patients (19.7%) randomized to fidaxomicin therapy experienced another recurrence within 4 weeks, compared with 22 of 62 (35.5%) patients randomized to treatment with vancomycin, reported lead investigator Dr. Oliver A. Cornely of the University of Cologne in Germany.

The findings add to the body of evidence supporting the superiority of fidaxomicin over vancomycin for the prevention of CDI recurrences, Dr. Cornely said, alluding to data from two North American and European phase III randomized controlled trials that enrolled a total of 1,164 patients in which he and his colleagues observed a 45%-50% reduction in the recurrence of CDI following an initial recurrence. The current investigation comprised a nested cohort of subjects from these trials who experienced a subsequent recurrence of CDI following treatment, he said.

The patients were at least 16 years old (mean age 63 years) with acute CDI symptoms and a positive stool toxin test. They were randomized to receive 200 mg of fidaxomicin twice daily or 125 mg of vancomycin four times daily, each for 10 days. The study end point was an additional CDI recurrence, defined as diarrhea and a positive stool test within 4 weeks, said Dr. Cornely at the conference, sponsored by the American Society for Microbiology.

Of the 13 recurrences in the fidaxomicin group, 5 occurred within the first 14 days following treatment and 8 occurred between days 15-40. In the vancomycin group, 17 of the recurrences occurred within the first 14 days and 5 occurred between days 15-40, Dr. Cornely reported. The rate of recurrence at 2 weeks was significantly different between the two groups, he said, noting that the later recurrences observed in the fidaxomicin group reflects the likelihood that these recurrences were the result of re-infection from the environment. In contrast, “the earlier recurrences following vancomycin treatment most likely were predominantly due to relapse from persistent spores in the GI tract.”

Because higher age is a known risk factor for recurrent CDI, the investigators separated the patients by age into three groups: 18-54 years; 55-74 years; and 75 years and older, and compared the recurrence rates between the groups. “The risk of second recurrence was 2.7-fold greater among patients 75 years and older, compared with those up to 55 years,” Dr. Cornely said, noting that no differences were observed in the rates of recurrence between patients in the 55-74 years and the 18-54 years groups.

“The efficacy of fidaxomicin at preventing CDI recurrence is likely due to its potent bactericidal activity against C. diff while sparing other protective spores,” Dr. Cornely said. Previous studies have demonstrated that fidaxomicin has a negligible impact on the intestinal flora, while vancomycin causes major perturbations of the anaerobic flora, he explained. “This may explain the differences between the two drugs in the prevention and treatment of recurrent CDI.”

The randomized, controlled phase III trials and the nested cohort study were funded by Optimer Pharmaceuticals, manufacturer of fidaxomicin. The drug is “the first in a new class of antibiotics called macrocycles, which inhibit the bacterial enzyme RNA polymerase, resulting in the death of C. difficile,” according to the drug company.

Dr. Cornely provided no additional disclosures.

BOSTON – Fidaxomicin is superior to vancomycin for the treatment of recurrent Clostridium difficile infection, investigators reported Sept. 14 at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

In a randomized controlled trial comparing the efficacy of fidaxomicin, a narrow-spectrum macrocyclic antibiotic, and vancomycin in 128 patients with recurrent Clostridium difficile infection (CDI) within 90 days of treatment for the initial CDI episode, fidaxomicin was associated with a 45% reduction in a subsequent CDI recurrence relative to vancomycin. Specifically, 13 of 66 patients (19.7%) randomized to fidaxomicin therapy experienced another recurrence within 4 weeks, compared with 22 of 62 (35.5%) patients randomized to treatment with vancomycin, reported lead investigator Dr. Oliver A. Cornely of the University of Cologne in Germany.

The findings add to the body of evidence supporting the superiority of fidaxomicin over vancomycin for the prevention of CDI recurrences, Dr. Cornely said, alluding to data from two North American and European phase III randomized controlled trials that enrolled a total of 1,164 patients in which he and his colleagues observed a 45%-50% reduction in the recurrence of CDI following an initial recurrence. The current investigation comprised a nested cohort of subjects from these trials who experienced a subsequent recurrence of CDI following treatment, he said.

The patients were at least 16 years old (mean age 63 years) with acute CDI symptoms and a positive stool toxin test. They were randomized to receive 200 mg of fidaxomicin twice daily or 125 mg of vancomycin four times daily, each for 10 days. The study end point was an additional CDI recurrence, defined as diarrhea and a positive stool test within 4 weeks, said Dr. Cornely at the conference, sponsored by the American Society for Microbiology.

Of the 13 recurrences in the fidaxomicin group, 5 occurred within the first 14 days following treatment and 8 occurred between days 15-40. In the vancomycin group, 17 of the recurrences occurred within the first 14 days and 5 occurred between days 15-40, Dr. Cornely reported. The rate of recurrence at 2 weeks was significantly different between the two groups, he said, noting that the later recurrences observed in the fidaxomicin group reflects the likelihood that these recurrences were the result of re-infection from the environment. In contrast, “the earlier recurrences following vancomycin treatment most likely were predominantly due to relapse from persistent spores in the GI tract.”

Because higher age is a known risk factor for recurrent CDI, the investigators separated the patients by age into three groups: 18-54 years; 55-74 years; and 75 years and older, and compared the recurrence rates between the groups. “The risk of second recurrence was 2.7-fold greater among patients 75 years and older, compared with those up to 55 years,” Dr. Cornely said, noting that no differences were observed in the rates of recurrence between patients in the 55-74 years and the 18-54 years groups.

“The efficacy of fidaxomicin at preventing CDI recurrence is likely due to its potent bactericidal activity against C. diff while sparing other protective spores,” Dr. Cornely said. Previous studies have demonstrated that fidaxomicin has a negligible impact on the intestinal flora, while vancomycin causes major perturbations of the anaerobic flora, he explained. “This may explain the differences between the two drugs in the prevention and treatment of recurrent CDI.”

The randomized, controlled phase III trials and the nested cohort study were funded by Optimer Pharmaceuticals, manufacturer of fidaxomicin. The drug is “the first in a new class of antibiotics called macrocycles, which inhibit the bacterial enzyme RNA polymerase, resulting in the death of C. difficile,” according to the drug company.

Dr. Cornely provided no additional disclosures.

BOSTON – Fidaxomicin is superior to vancomycin for the treatment of recurrent Clostridium difficile infection, investigators reported Sept. 14 at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

In a randomized controlled trial comparing the efficacy of fidaxomicin, a narrow-spectrum macrocyclic antibiotic, and vancomycin in 128 patients with recurrent Clostridium difficile infection (CDI) within 90 days of treatment for the initial CDI episode, fidaxomicin was associated with a 45% reduction in a subsequent CDI recurrence relative to vancomycin. Specifically, 13 of 66 patients (19.7%) randomized to fidaxomicin therapy experienced another recurrence within 4 weeks, compared with 22 of 62 (35.5%) patients randomized to treatment with vancomycin, reported lead investigator Dr. Oliver A. Cornely of the University of Cologne in Germany.

The findings add to the body of evidence supporting the superiority of fidaxomicin over vancomycin for the prevention of CDI recurrences, Dr. Cornely said, alluding to data from two North American and European phase III randomized controlled trials that enrolled a total of 1,164 patients in which he and his colleagues observed a 45%-50% reduction in the recurrence of CDI following an initial recurrence. The current investigation comprised a nested cohort of subjects from these trials who experienced a subsequent recurrence of CDI following treatment, he said.

The patients were at least 16 years old (mean age 63 years) with acute CDI symptoms and a positive stool toxin test. They were randomized to receive 200 mg of fidaxomicin twice daily or 125 mg of vancomycin four times daily, each for 10 days. The study end point was an additional CDI recurrence, defined as diarrhea and a positive stool test within 4 weeks, said Dr. Cornely at the conference, sponsored by the American Society for Microbiology.

Of the 13 recurrences in the fidaxomicin group, 5 occurred within the first 14 days following treatment and 8 occurred between days 15-40. In the vancomycin group, 17 of the recurrences occurred within the first 14 days and 5 occurred between days 15-40, Dr. Cornely reported. The rate of recurrence at 2 weeks was significantly different between the two groups, he said, noting that the later recurrences observed in the fidaxomicin group reflects the likelihood that these recurrences were the result of re-infection from the environment. In contrast, “the earlier recurrences following vancomycin treatment most likely were predominantly due to relapse from persistent spores in the GI tract.”

Because higher age is a known risk factor for recurrent CDI, the investigators separated the patients by age into three groups: 18-54 years; 55-74 years; and 75 years and older, and compared the recurrence rates between the groups. “The risk of second recurrence was 2.7-fold greater among patients 75 years and older, compared with those up to 55 years,” Dr. Cornely said, noting that no differences were observed in the rates of recurrence between patients in the 55-74 years and the 18-54 years groups.

“The efficacy of fidaxomicin at preventing CDI recurrence is likely due to its potent bactericidal activity against C. diff while sparing other protective spores,” Dr. Cornely said. Previous studies have demonstrated that fidaxomicin has a negligible impact on the intestinal flora, while vancomycin causes major perturbations of the anaerobic flora, he explained. “This may explain the differences between the two drugs in the prevention and treatment of recurrent CDI.”

The randomized, controlled phase III trials and the nested cohort study were funded by Optimer Pharmaceuticals, manufacturer of fidaxomicin. The drug is “the first in a new class of antibiotics called macrocycles, which inhibit the bacterial enzyme RNA polymerase, resulting in the death of C. difficile,” according to the drug company.

Dr. Cornely provided no additional disclosures.