From the Journals

Healthy donor stool safe, effective for recurrent CDI

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Results highlight value of trials

Kelly and her colleagues demonstrate that rigorous controlled trials are valuable even when we think we know the answer. Their results prompt us to ask again whether microbial manipulation has any as-yet unappreciated health benefits or risks and whether there are preferred microbiomes for specific human populations or locales.

Careful review of reported adverse events in the current trial is instructive. One participant reported a 9.1-kg weight gain (donor details were not provided), a problem previously described in a separate case report. There is great interest in understanding whether the microbiome can be manipulated to modify weight in humans, as has been clearly shown in mice. In addition, patients receiving donor stool more frequently reported chills. In my own practice, I have rarely observed transient fever after healthy donor FMT delivered orally in encapsulated form, and I hypothesize that this may be due to an immune reaction to a new microbial ecosystem. Patients considering FMT should be informed of both of these possible adverse events.

Elizabeth L. Hohmann, MD, is at Massachusetts General Hospital, Boston. She reported grant support and personal fees from Seres Therapeutics outside the submitted work. These comments are from an editorial accompanying the article (Ann Intern Med. 2016 Aug 22. doi: 10.7326/M16-1784).

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For patients with recurrent Clostridium difficile infection (CDI), donor stool administered via colonoscopy seemed safe and achieved clinical cure significantly more often than autologous fecal microbiota transplantation (FMT), based on a small trial reported online in Annals of Internal Medicine.

In all, 20 of 22 patients (91%) achieved cure with donor FMT, compared with 63% of patients who received their own markedly dysbiotic stool (P = .04), reported Colleen Kelly, MD, of The Miriam Hospital, Providence, R.I., together with her associates. “Differences in efficacy between sites suggest that some patients with lower risk for CDI recurrence may not benefit from FMT. Further research may help determine the best candidates,” the researchers wrote.

Dr. Colleen Kelly

Dr. Colleen Kelly

FMT corrects the dysbiosis associated with CDI and is recommended in the event of failed antibiotic therapy leading to a third episode of infection. But this advice is based mainly on case series and open-label trials, the researchers noted. Their dual-center, randomized, controlled, double-blinded study included 46 patients with at least three recurrences of CDI who had completed a course of vancomycin during their most recent episode of infection. Patients older than age 75 years or who were immunocompromised were excluded (Ann Intern Med. 2016 Aug 22. doi: 10.7326/M16-0271).

The overall clinical cure rates reflected the literature, the researchers reported, and all nine patients who developed CDI after autologous FMT were subsequently cured by donor FMT. Indeed, donor FMT “restored normal microbial community structure, with reductions in Proteobacteria and Verrucomicrobia and increases in Bacteroidetes and Firmicutes. In contrast, microbial diversity did not improve after autologous FMT.”

Notably, however, 90% of autologous FMT patients at the center in New York achieved clinical cure, compared with 43% of patients at the center in Rhode Island. Further analyses revealed differences between patients and fecal microbiota at the two sites, the investigators said. Patients in New York typically had CDI for longer, with more recurrences and up to 148 weeks of vancomycin and other antibiotics. Thus, they might have been cured before enrollment. But “autologous FMT patients at the New York site [also] had greater abundances of Clostridia, raising the possibility of emergence of microbial community assemblages inhibitory to C. difficile via competitive niche exclusion, or possibly by emergence of nontoxigenic organisms,” the researchers wrote.

There were no serious adverse effects associated with either type of FMT, they noted.

Dr. Kelly disclosed ties to Seres Health outside the submitted work. Two coauthors had patents or patents pending for “compositions and methods for transplantation of colon microbiota.” A third coauthor disclosed ties to OpenBiome and personal fees from CIPAC/Crestovo outside the submitted work. The remaining coauthors had no conflicts of interest.

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