What Do the FDA and Feces Have in Common?

A couple weeks ago I wrote a little bit about my mother’s battle with colorectal cancer last year, alluding to a future post concerning post-surgery infections. Well, the time seems as apropos as any considering the FDA’s recent kibosh on fecal transplants (FT). On the one hand, improved regulations are needed, so I commend them for kinda getting the idea that something needs to be done; there are after all a great number of microbiome-promoting charlatans out there whose safety standards are, shall we say, less than desirable and sometimes downright deadly. On the other hand, let’s face it, the FDA doesn’t seem to be using their brains on this one. Rather than designing a standard protocol that practitioners are required to follow, instead the FDA has mandated that every potential FT practitioner must send them a copy of their protocol for approval.

Seriously? Rather than taking the time to review the literature and design a standard protocol, the FDA instead prefers to expend extraordinary amounts of time– that of practitioners and FDA personnel alike!– in writing and reviewing EVERY… SINGLE… PROTOCOL.

dumbass_kit

This blog today is partially an opinion piece. So here’s the opinion part of it: it seems to me like the FDA gives fecal transplant little genuine credit as a viable treatment modality and their mandates are a way to quash progress rather than reasonably ensure safety. True, much more research needs to be done into the matter and tighter regulations are necessary. But there are ways in which regulations can either support and allow safe treatments to flourish or place a stranglehold on their development. In the case of the FDA’s recent gesture, I personally would class their actions as the latter. Granted, that’s just my opinion, but their positive support of a treatment with such potential is decidedly underwhelming.

A lot of the evidence out there is anecdote. But unlike most stories, the few stats being reported offer some pretty astounding rates of recovery with so simple a procedure. Just for the sheer possibility that these success rates could be true, medical research should be biting at the bit to study this. It’s curious why this hasn’t happened. Is it primarily because this topic centers around poo? Who knows.

For those unaware of what I’m talking about or why I’m so upset, I’m mainly referring to hospital-borne Clostridium difficile (C diff) bacterial infections. We’ve all heard the joke that if you’re ill one of the last places you want to be is at a hospital. But there’s more than a grain of truth to that and hospital-borne infections, particularly virulent monster strains like the C diff that roam many of its wards, pose an enormous threat to patient recovery and overall safety.

As an example, my mother was diagnosed with an early stage colorectal cancer. She went in for the surgery, scared to death about the cancer itself. She came out of it, all seemed to have gone well, and we took her home to recover thinking that the worst was over. Within two weeks she was not improving but instead felt worse than she had when she’d left the hospital, and by a month’s time she was so ill with constant diarrhea, extreme dehydration, weight loss, and horrific sleep deprivation that she required another hospital stay in order to try and stabilize her. Even though the word “cancer” is enough to scare anybody, she will tell you readily that cancer was the easy part and it was the post-surgery infection that gave her the closest brush with mortality. She required two more lengthy rounds of heavy antibiotics to get the C diff under control. But if something like FT had been immediately available to her at the start of her symptoms, presuming she would’ve responded to the treatment, just imagine the pain it would’ve saved her, not to mention the hospital bills.

It seems a decidedly human hang-up that when we realize an approach to a problem isn’t working then we try the same approach but harder. You have a tiny nail in the wall and if you can’t manage it with a hammer, what do you do? Select a sledgehammer of course. How infrequently do we take a few steps back from a problem, think, and utilize a truly different approach based on reason. In the case of C diff, this monster bug was bred by overuse of antibiotics and other sanitizers that do little to destroy its spores. Instead, we destroy many of its natural microbial antagonists such as the lactobacilli strains and yeast, which allows it free reign over once-limited resources. With antibiotic overuse in patients, hospitals have also bred the C diff superbug, a form which is even less resistant to antibiotics and one which produces even more cytotoxins leading to deadlier cases of infection. Aside from the misery of frequent explosive diarrhea, there is risk of colonic necrosis necessitating further surgery to remove the dead tissue, and other risky complications. In the case of my mother, she was lucky that her cancer only required surgery, but imagine the many cancer patients who have similar surgeries and who require subsequent chemotherapy. In general, oncologists won’t begin chemo while a patient has an infection like C diff, and recurrent C diff infections can take many months to get over. Imagine the amount of time that person is losing in the treatment of their cancer while doctors give them round after round of antibiotics in the hopes of quelling the rampant infection.

To complicate matters, it’s generally not healthy individuals who get C diff infections. It’s usually those whose presentation is complicated by age and/or ill health. And it’s not just being at a hospital that promotes infection but the use of antibiotics in that setting. In my mother’s case, she was given a broad spectrum antibiotic just prior to surgery. In the old days, i.e., the 1990s, doctors found that pre-operative oral antibiotics helped to quell post-surgery infections [1]. So, yes, the intention is good, but nowadays we have these nasty superbugs that throw a decided wrench into the works. So the same old practices are becoming antiquated and downright dangerous. To illustrate this point, Kassam et al. (2012) review that in the year 2000 the rate of uncomplicated C diff infection was 2.5%, but by 2012 that rate had skyrocketed to 18%.

And here’s the kicker: what do we still use to treat this horrible C diff superbug? More antibiotics of course! Mr. Nail, meet Mr. Sledgehammer.

nail_sledgehammer

Do we never learn? How long is it going to take us to realize that using the same old solutions to new problems is going to get patients killed?

Thankfully, though the studies are small in number, research interest in FT as an alternative and even first-line treatment for C diff is growing and there have been a few more studies into its efficacy. For instance, Rohlke et al. (2010) found in their sample that 18 of their 19 patients responded immediately to FT and meanwhile the final patient responded following a second FT. This, however, did not completely prevent reinfection. A more recent study by Kassam et al. published in JAMA Internal Medicine in 2012 reported results of FT treatment in a cohort of 27 patients. 25 of the 27 (93%) experienced remission, 22 of which remitted within the 24 hour period following administration.

The results thus far are extraordinarily promising. But so little progress has been made in the last decade in terms of medical practice. Consider how little has been done since an earlier study by Aas et al. (2003) in which 15 of 18 patients treated with FT experienced full remission, up to present day in which the same types of small-scale studies continue to report similar rates of success. And yet we are little closer to the organized application of this treatment to the growing rates of C diff infection.

As others have readily noted, practicing and regulatory bodies are more than willing to apply antibiotics which devastate a patient’s microbial ecosystem, but are extraordinarily reluctant to utilize microbiota to naturally combat infections. As microbiome-spouting charlatan practitioners are excellent reminders, caution is warranted. Fecal matter contains many and variable types of bacteria and fungi, which prevents standardized treatment and a certain level of control by the practitioner. In short, in such a transplant we don’t know everything we’re transplanting. And the unforeseen is always reason for fear and hesitation.

But at some point the risk of the known outweighs the risk of the unknown. In individuals who are truly suffering and whose lives may be endangered by such infection, to refuse them transplantation is simply unethical.

First, do no harm.

Update: Since I had written this blog, it seems that the FDA has backed down on its mandate requiring doctors to apply for approval to practice fecal transplants. Read more here: http://www.nbcnews.com/health/fda-backs-away-new-fecal-transplant-rules-6C10370978

10 responses to “What Do the FDA and Feces Have in Common?

    • Thank you, jaksichja.Thankfully my mother is doing well, although bowel function will probably never be 100% with the damage to her microbial ecosystem. I’d say she’ll remain about 85% functional. This stuff can be truly rough– and deadly. My mother, in her own informal research, had told me that approximately 90,000 deaths per year are due to C diff, over half of which are associated with hospital stays. A truly frightening statistic.

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