Tag Archives: C difficile Infection Treatment Option

Study Investigators Find Combination of Vancomycin and FMT Superior In Treating Recurrent C.difficile Infection (rCDI)

The combination of vancomycin and fecal microbiota transplantation was found to be superior to fidaxomicin or vancomycin in the treatment of patients with recurrent Clostridium difficile infection (rCDI), according to a study published in Gastroenterology.

This randomized, single-center trial was designed to compare the efficacy of fecal microbiota transplantation with that of fidaxomicin and vancomycin.

Sixty-four adults with recurrent CDI seen at a gastroenterology clinic in Denmark between April 5, 2016 and June 10, 2018 were randomly assigned to a group receiving fecal microbiota transplantation applied by colonoscopy or nasojejunal tube after 4 to 10 days of 125 mg vancomycin 4 times daily (n=24), or 10 days of 200 mg fidaxomicin 2 times daily (n=24), or 10 days of 125 mg vancomycin 4 times daily (n=16).

Patients experiencing a CDI recurrence after this course of treatment, and those who could not be randomly assigned were provided rescue fecal microbiota transplantation. The primary study outcome was combined clinical resolution and negative polymerase chain reaction test for C difficile toxin at 8 weeks post-treatment, and secondary end points included week 8 clinical resolution.

The combination of negative C difficile test results and clinical resolution was observed in 71% of the 24 participants who received fecal microbiota transplantation (95% CI, 49-87%; n=17), 33% of the 24 participants who received fidaxomicin (95% CI, 16-55%; n=8), and 19% of the 16 participants (95% CI, 5-46%; n=3) who received vancomycin (fecal microbiota transplantation vs fidaxomicinP=.009; fecal microbiota transplantation vs vancomycin, P=.001; fidaxomicin vs vancomycin, P=.31). Clinical resolution was observed in 92% of participants who received fecal microbiota transplantation (n=22; P=.0002), 42% of participants who were treated with fidaxomicin (n=10; <.0001), and 19% of participants who were treated with vancomycin (n=3; P=.13). No significant differences in results were seen between patients receiving initial fecal microbiota transplantation therapy and those who received rescue treatment with such a transplant.

Of note, adverse events (transient abdominal pain, constipation, bloating and diarrhea) were observed in 10 of the participants who received a fecal microbiota transplant, 1 of which was classified as severe.

Researchers noted limitation of a lack of patients with C difficile ribotype 027, such that results may not be generalizable to settings with a high ribotype 027 frequency. Study interventions were also unblinded, introducing the possibility of observer bias, although the C difficile toxin test was applied to all patients at all time points in an effort to obtain objective outcome measures.

Study investigators concluded, “[fecal microbiota transplantation] was superior to both fidaxomicin and vancomycin monotherapies for [recurrent] CDI, with regard to both combined clinical and microbiological resolution and clinical resolution alone.”

Reference

https://www.infectiousdiseaseadvisor.com/respiratory/new-powder-formulation-tuberculosis-vaccine-candidate-is-in-human-trial/article/829508/

Hvas CL, Jørgensen SMD, Jørgensen SP, et al. Fecal microbiota transplantation is superior to fidaxomicin for treatment of recurrent Clostridium difficile infection [published online January 2, 2019]. Gastroenterology. doi: 10.1053/j.gastro.2018.12.019

Comparison Study Shows Efficacy in Frozen Fecal Product To Fresh For Fecal Microbiota Transplantation To Treat Recurrent C. diff. Infections

Frozen fecal microbiota transplantation showed efficacy comparable to fresh FMT for clinical resolution of diarrhea among adult patients with recurrent or refractory Clostridium difficile infection, according to results of a randomized trial published in JAMA.

Using frozen FMT would reduce costs associated with donor screening frequency, provide immediate availability of the treatment and enable delivery of the treatment to centers without on-site laboratory facilities,

the researchers wrote. “Previous studies have supported the use of frozen FMT for management of recurrent [C. difficile infection] but have not directly compared frozen with fresh FMT.”

Lee CH, et al. JAMA. 2016;doi:10.1001/jama.2015.18098

Malani PN, Rao K. JAMA. 2016;doi:10.1001/jama.2015.18100

Christine H. Lee, MD, from McMaster University in Canada, and colleagues, conducted a double-blind, noninferiority trial involving 232 adult patients with recurrent or refractory C. difficile infection (CDI) at six Canadian academic medical centers from July 2012 to September 2014. Patients were randomly assigned to receive frozen (n = 114) or fresh (n = 118) FMT via enema without bowel preparation, and if they showed no improvement by day 4, they received an additional FMT between days 5 and 8.

No recurrence of CDI-related diarrhea at 13 weeks and adverse events served as primary outcomes, and a 15% margin was set to confirm noninferiority.

In the per-protocol population (frozen, n = 91; fresh, n = 87), 83.5% of the frozen FMT group achieved clinical resolution compared with 85.1% of the fresh FMT group, a difference of – 1.6% (95% CI, – 10.5% to ∞; P = .01 for noninferiority). In the modified intention-to-treat population (frozen, n = 108; fresh, n = 111), 75% of the frozen FMT group achieved clinical resolution compared with 70.3% of the fresh FMT group, a difference of 4.7% (95% CI, – 5.2% to ∞; P < .001 for noninferiority). Adverse and serious adverse events were comparable between groups; the most common adverse events were transient diarrhea (70%), abdominal cramps (10%) or nausea (< 5%) during the 24 hours after FMT, and constipation (20%) and excess flatulence (25%) during follow-up, all mild to moderate in severity.

“Among adults with recurrent or refractory CDI, the use of frozen compared with fresh FMT did not result in worse proportion of clinical resolution of diarrhea,” the researchers concluded. “Given the potential advantages of providing frozen FMT, its use is a reasonable option in this setting.”

These researchers have provided

“the best evidence to date supporting the use of frozen stool, with their finding that use of frozen stool for FMT resulted in a rate of clinical resolution of diarrhea that was no worse than that obtained with fresh stool for FMT and will likely expand the availability of FMT for patients with recurrent CDI,”

Preeti N. Malani, MD, MSJ, associate editor of JAMA, and Krishna Rao, MD, MS, both from the University of Michigan Health System, Ann Arbor, wrote in a related editorial. “The ability to use frozen stool eliminates many of the logistical burdens inherent to FMT, because stool collection and processing need not be tied to the procedure date and time.

This study also provides greater support for the practice of using centralized stool banks, which could further remove barriers to FMT by making available to clinicians safe, screened stool that can be shipped and stored frozen and thawed for use as needed. In theory, procedure costs may also be decreased, since comprehensive donor screening is expensive.” – by Adam Leitenberger

Disclosures: Lee reports she has participated in clinical trials for ViroPharma, Actelion, Cubist and Merck, and served as a member of the advisory boards for Rebiotix and Merck. Please see the study for a full list of all other researchers’ relevant financial disclosures. Malani and Rao report no relevant financial disclosures.dR

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