January 17th, 2013

Why the Results of the C Diff Study (You Know Which One) Were No Surprise

In cased you missed it, fecal transplant — use of poop from a healthy donor, which is then infused into the colon either from above (nasogastric tube) or below (colonoscope) — is unquestionably the most effective treatment for people who have multiple recurrences of C. difficile colitis (C diff).

We know this because of a randomized study just published in the New England Journal of Medicine. Here’s the punch line:

The study was stopped after an interim analysis. Of 16 patients in the infusion group, 13 (81%) had resolution of C. difficile–associated diarrhea after the first infusion. The 3 remaining patients received a second infusion with feces from a different donor, with resolution in 2 patients. Resolution of C. difficile infection occurred in 4 of 13 patients (31%) receiving vancomycin alone and in 3 of 13 patients (23%) receiving vancomycin with bowel lavage (P<0.001 for both comparisons with the infusion group).

A slam dunk win for fecal transplant, so much so that there was no point even completing the study. In the New York Times right now, coverage of the paper is actually their most e-mailed story, and even the non-clinicians in our office are buzzing about it.

(Inevitably with giggles and jokes. This stuff is hard for people to talk about, but they somehow can’t resist.)

But many of us in the ID world knew that fecal transplant was going to work great for C diff even before this study. How did we know?

  1. The current treatment for recurrent C diff is terrible. Metronidazole, vancomycin, and fidaxomicin all share a basic problem. They are antibiotics. And antibiotics cause C diff to begin with. Fail.
  2. Probiotics don’t do much. As much as I’d wish to say otherwise, the efficacy data for probiotics in preventing C diff relapse are marginal at best. Remember, lots of what makes up “normal” flora can’t even be cultured — so how do you put those bugs in a capsule? Looks like we need to use the real thing to get those normal bacteria back.
  3. The published uncontrolled studies on use of fecal transplant were extraordinarily favorable. In this systematic review, the cure rate was 92%. And remember, the people referred for these procedures were horribly weakened by recurrent C diff, and many had severe underlying medical conditions.
  4. Our limited anecdotal experience confirmed that this actually works. One of the local gastroenterologists has been doing this for a couple of years. Our first referral was an 84-year-old man with two forms of cancer, diabetes, and 5 episodes of recurrent C diff, bad enough that he’d lost more than 15% of his baseline weight. One fecal transplant procedure — C diff gone.
  5. For patients and doctors to keep doing something this disgusting, it must be effective. There’s a reason we snicker and jest when discussing fecal transplants — it’s gross and makes us uncomfortable. Just look at all the various euphemisms out there for this procedure — intestinal microbiota transplantation, fecal biotherapy, bacteriotherapy, human probiotic infusion. (That last one is my personal favorite — you can even call it “HPI.”) Anything to get rid of that nasty image of having other people’s poop inside of us, yuck. Sorry for mentioning that.

So consider the publication of this landmark article as a way of getting the word out to the rest of the world that this unsavory — but undoubtedly very effective — treatment is here to stay.

Let’s just hope they can find another important job for C diff Cliff.

10 Responses to “Why the Results of the C Diff Study (You Know Which One) Were No Surprise”

  1. AH says:

    I’m so far ahead of this curve. Rabbit vets have been treating rabbits in GI stasis with this method for at least a decade–my rabbit Mojo donated to the cause at one point.

  2. Tom Saps says:

    Sure, but why do you need to use a colonoscope? An enema bag is just as effective. Oh wait, it’s an American study. An enema bag wouldn’t allow the patient to be charged as much for the procedure. That goes for the blender too. A sterile water bottle with the sample emulsified using vigorous shaking works just fine.

  3. PC says:

    Enemas do not typically reach the transverse or the right colons, so in theory would be inferior to colonoscopic deliveries. Obviously no H2H studies exist.

    However, fecal transplant through ND tubes should be just as effective as colonoscopies, and much less expensive. ND tubes are probably preferred over NG tubes also — even if they can be slightly more cumbersome to place — since post-pyloric deliveries probably help minimize/eliminate the “feculent breath” scenario that gastric deliveries can face.

  4. jon says:

    isnt this a “julia enema” a very old thing?

  5. Dirk says:

    Nature is always right, and somehow this study just confirms why some animals, e.g. elephants, perform ‘coprophagia’ when they feel not well! If you have a dog, you may have noticed with certain disgust the same behaviour.

  6. Loretta S says:

    “They are antibiotics. And antibiotics cause C diff to begin with. Fail.” Thank you for saying EXACTLY what I have always thought!

  7. Luba K says:

    Logical thinking. Now let’s tackle MRSA.

  8. Harvey Pollack says:

    I recall hearing of this in medical school from our ID attending some years ago, in the context of using a chocolate milkshake with fecal matter mixed in.

  9. OK says:

    I learned this thing in the first year of my residency (2005) but somehow it never became a standard therapy…hope this study will make us finally accept what might be the best way to go!

  10. Helmut Albrecht says:

    Just to mention, this requires a little more effort than most people assume. We have treated this as a transplant and it requires pretty extensive donor testing.
    The colonoscopy approach actually IS vastly more effective (and there are several studies now) but I will admit that even I (as a former GI doc) believe that most of the colonoscopy benefit is the bowel prep that mechanically removes most spores/bacteria. The NG tube scenario is just nasty (try picturing burping up somebody else’s stool) and there is some dose dependency in this (the more the better) which would make you use amounts that you really do not want to place in the upper GI tract to avoid the oops mentioned above

    Regardless of all of this, the procedure remains the only transplant where it is much better to be the donor than the recipient. And BTW, if you understand the biology and the difference between tapering (makes no sense) and pulse dosing you can >99% of patients through this with those dreaded antibiotics.

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

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