In the Journals

FMT ‘highly effective’ for recurrent, refractory C. difficile infection, regardless of preparation, delivery

Fecal microbiota transplantation was highly effective for treating recurrent or refractory Clostridium difficile infection, independent of preparation and delivery route, according to the results of a new systematic review and meta-analysis.

“Over the past decade or so, FMT has been studied by several centers worldwide for management of recurrent and refractory CDI,” U.K. investigators wrote. “However, uncontrolled studies make up the bulk of the supporting evidence. Previous systematic reviews and meta-analyses either have methodological limitations as they have a restrictive selection criteria, do not have a comprehensive search strategy or do not consider the effect of different modalities of preparation or delivery of FMT. Moreover, they do not include the most recent evidence, which to date includes more than five [randomized controlled trials].”

Therefore, the researchers reviewed medical literature on FMT for recurrent and refractory CDI published up to October 2016, and ultimately included seven RCTs and 30 case series in their analysis, involving 1,973 patients with 428 enrolled in RCTs. Clinical resolution of CDI served as the primary outcome, but the researchers also performed subgroup analyses of delivery routes and different FMT preparations.

They found that FMT was superior to vancomycin for resolution of recurrent and refractory CDI (RR = 0.23; 95% CI, 0.07-0.8), with a pooled clinical resolution rate of 92% (95% CI, 89-94).

Subgroup analyses showed that FMT delivered via the lower GI tract was significantly more effective than FMT delivered via the upper GI tract (95% vs. 88%; P = .02). Further, they found no significant difference between fresh and frozen FMT preparations (92% vs. 93%).

They also found that consecutive courses of FMT after initial failure showed an incremental effect, and that donor screening was consistent but recipient preparation and volume varied.

Finally, they noted that serious adverse events were rare, and concluded that FMT therefore appears to be a safe and effective treatment strategy for recurrent and refractory CDI.

“Even the most conservative analysis gives an estimate of 49% response rate for FMT in this setting based on the lower prediction interval for a single infusion,” they wrote.

They acknowledged that the data “are relatively heterogeneous with regard to the methodology for transplantation and the outcome measure for resolution of CDI. While this could be explored with the current evidence base to refine estimates and potentially suggest effect modifiers, the effect of FMT on resolution of recurrent/refractory CDI is markedly evident and appears to be quantitatively in excess of that seen with other anti-microbial therapies such as vancomycin.”

Further research should focus on determining optimal procedures and long-term outcomes and side effects, they concluded. – by Adam Leitenberger

Disclosures: The researchers report no relevant financial disclosures.

 

Fecal microbiota transplantation was highly effective for treating recurrent or refractory Clostridium difficile infection, independent of preparation and delivery route, according to the results of a new systematic review and meta-analysis.

“Over the past decade or so, FMT has been studied by several centers worldwide for management of recurrent and refractory CDI,” U.K. investigators wrote. “However, uncontrolled studies make up the bulk of the supporting evidence. Previous systematic reviews and meta-analyses either have methodological limitations as they have a restrictive selection criteria, do not have a comprehensive search strategy or do not consider the effect of different modalities of preparation or delivery of FMT. Moreover, they do not include the most recent evidence, which to date includes more than five [randomized controlled trials].”

Therefore, the researchers reviewed medical literature on FMT for recurrent and refractory CDI published up to October 2016, and ultimately included seven RCTs and 30 case series in their analysis, involving 1,973 patients with 428 enrolled in RCTs. Clinical resolution of CDI served as the primary outcome, but the researchers also performed subgroup analyses of delivery routes and different FMT preparations.

They found that FMT was superior to vancomycin for resolution of recurrent and refractory CDI (RR = 0.23; 95% CI, 0.07-0.8), with a pooled clinical resolution rate of 92% (95% CI, 89-94).

Subgroup analyses showed that FMT delivered via the lower GI tract was significantly more effective than FMT delivered via the upper GI tract (95% vs. 88%; P = .02). Further, they found no significant difference between fresh and frozen FMT preparations (92% vs. 93%).

They also found that consecutive courses of FMT after initial failure showed an incremental effect, and that donor screening was consistent but recipient preparation and volume varied.

Finally, they noted that serious adverse events were rare, and concluded that FMT therefore appears to be a safe and effective treatment strategy for recurrent and refractory CDI.

“Even the most conservative analysis gives an estimate of 49% response rate for FMT in this setting based on the lower prediction interval for a single infusion,” they wrote.

They acknowledged that the data “are relatively heterogeneous with regard to the methodology for transplantation and the outcome measure for resolution of CDI. While this could be explored with the current evidence base to refine estimates and potentially suggest effect modifiers, the effect of FMT on resolution of recurrent/refractory CDI is markedly evident and appears to be quantitatively in excess of that seen with other anti-microbial therapies such as vancomycin.”

Further research should focus on determining optimal procedures and long-term outcomes and side effects, they concluded. – by Adam Leitenberger

Disclosures: The researchers report no relevant financial disclosures.

 

    Perspective

    Jessica R. Allegretti

    This is a nicely done, very thorough updated review that includes the newer RCTs that assess fresh vs. frozen material, colonoscopy vs. capsule administration, and high vs. low dose capsules.

    While significant heterogeneity exists between these studies, the authors conclude that FMT is effective independent of preparation of or delivery modality, which further expands on our current knowledge that FMT is an extremely effective therapy for recurrent CDI.

    • Jessica R. Allegretti, MD, MPH
    • Crohn's and Colitis Center
      Brigham and Women's Hospital
      Harvard Medical School

    Disclosures: Allegretti reports no relevant financial disclosures.