more tolerable fecal transplant for resistant c diff infections

so, yet another positive but small fecal transplant study for relapsing c diff infection, from the same group who reported earlier this year (see prior blog from 5/11/14, appended below), this time using (more tolerable/acceptable) oral capsules. on the ever recurrent microbiome theme, the point of these fecal transplants is to re-establish a healthy microbiome directly, as opposed to decimating the diseased microbiome with aggressive antibiotics (vanco, metronidazole). in this open-labeled study, 20 patients (median age 64.5, range 11-89) with at least 3 episodes of mild-to-moderate c diff infections who had failed 6-8 week tapers with vanco (with or without other antibiotic, including metronidazole or the very expensive fidaxomicin) or at least 2 severe episodes of c diff requiring hospitalization were given 15 capsules of frozen fecal microbiota transplant (FMT) from an unrelated donor for 2 consecutive days and followed up to 6 months (see cdiff fecal tx jama 2014 in dropbox, or doi:10.1001/jama.2014.13875​). stool was harvested (if that is the correct term) from 4 healthy volunteers. mean capsule storage was 113 days at -80 C. results:

--resolution of diarrhea in 14 of the 20 (70%, with CI 47-85%) after a single treatment with FMT
--the 6 nonresponders were retreated: 4 had resolution (ie, total of 90%). nonresponders were defined as no change in diarrhea after 72 hours, retested and found positive for c diff.
--effect pretty quick: daily number of bowel movements decreased from 5 the day prior to FMT, to 2 at day 3 and 1 at 8 weeks, with attendant increases in self-ranked health status
--interesting that 9 of the patients (who all failed antibiotic therapy) had received the new and likely more powerful fidaxomicin​, and 6 resolved after only 1 treatment with FMT
--no serious adverse effects, no vomiting and only mild abdominal cramping and bloating in 6 patients.

so, FMT seems to work in this difficult, non-responsive group of patients with relapsing c diff infections. although we need confirmation from both larger studies and studies done at different institutions, it all seems pretty promising and reflects a significant ideological shift: we should certainly do everything we can to decrease microbiome destruction (in this case, largely by avoiding unnecessary antibiotics and using as narrow-spectrum as possible -- for example, using trimethoprim/sulfa instead of cipro for simple UTIs), and once the microbiome is disrupted, restore it with a healthy one instead of hitting it with more antibiotics (in fact, the antibiotics used seem to have increasing failure rates, now 30% for first occurrences and 60% for treatment failures!!). one advantage of this study is that FMT is scalable: does not require fresh stool from healthy donors which has to be screened (and is only good for 6 hours), limited availability, etc, and it uses stool from unrelated donors/healthy volunteers (some prior studies used related donors, which might even be worse, as we learned with blood donations: the chance of transmitting infection was actually higher with related donors, who were likely reticent to mention their own exposures).