by Mike Miesen –
Contrary to expectations several weeks ago, on Monday the Food and Drug Administration relaxed regulations on the use of a cheap, safe, and very effective treatment for one of the most deadly hospital acquired infections, clostridium difficile (or c. diff). This is great news for individual patients and our health care system as a whole.
About that treatment: it’s not a hot new pharmaceutical – it’s poop. Fecal microbiota for transplantation (or FMT), to sound a bit more clinical. A fecal transplant.
The announcement, in bureaucratic English, the FDA:
… intends to exercise enforcement discretion regarding the IND [Investigational New Drug Application – the FDA’s process for testing a new therapeutic – Mike] requirements for the use of FMT to treat C. difficile infection not responding to standard therapies provided the treating physician obtains adequate informed consent from the patient or his or her legally authorized representative for the use of FMT products. Informed consent should include at a minimum, a statement that the use of FMT products to treat C. difficile is investigational and a discussion of its potential risks.
In everyday English: we won’t come after you for treating your patients with a fecal transplant. Go for it. But let’s back up a bit to explain what c. diff is, what a fecal transplant is, and why this is so important .
What’s c. diff?
C. diff is one of the most pernicious hospital acquired infections around, a pesky bacteria that causes an estimated 14,000 American deaths and $1 billion in spending annually. Patients – usually the elderly – pick up the bacteria from an unsanitary setting in the hospital; maybe a physician or nurse didn’t wash his or her hands, or the patient’s bed/room/bathroom wasn’t adequately cleaned (c. diff can’t be killed by many disinfectants, though bleach is effective).
Simply having c. diff in one’s colon isn’t typically enough to provoke an all-out assault – the bacteria just remains in the colon, controlled by the thousands of other bacteria and fungi that collectively makes up the gut “flora,” or microbiome.
Things get dicey once the microbiome is modified. C. diff is more difficult to treat than most other bacteria; a powerful antibiotic such as ciprofloxacin (every traveler’s favorite) will wipe out much in the gut microbiome, but not c. diff. Once the other bacteria is killed off, c. diff spreads, causing inflammation of the colon, which manifests symptomatically as diarrhea, abdominal pain, and fever in mild cases, septicemia in severe. Treatment has historically involved metronidazole or a vancomycin/rifaximin combo, which (typically) does works on c. diff.
But those antibiotic courses are long – up to a month – and only work initially 60% of the time; less often for a second or third bout of c. diff. Sometimes, a patient will have to be in a hospital bed to receive the treatment (in an isolation bed, which are always in high demand).
Fecal Transplants: Less Gross Than They Sound – and Extremely Effective
Enter fecal transplants. The theory behind the therapy is pretty simple: if the patient’s microbiome has changed, re-establishing floral homeostasis may bring the patient back to normal. The specific methods vary a bit, but in the most common, donor feces are collected, analyzed to ensure they’re bereft of a number of dangerous bacteria, diluted by saline or milk, then inserted into the patient’s colon by a nasoduodenal tube.
For reasons that basically amount to “eww, gross,” the procedure was historically used sparingly. A study published in the New England Journal of Medicine earlier this year changed that; researchers at the University of Amsterdam conducted a randomized controlled trial to study the efficacy of fecal transplants versus vancomycin therapy (with or without bowel lavage) for patients with recurrent c. diff infections.
So, what were the results? The researchers terminated the study, because the fecal transplants were overwhelmingly effective – 81% of treatment patients responded to the treatment after one transplant, versus 31% and 23% in the two control groups. Patients that were supposed to be in the control group were then given a fecal transplant instead.
A few caveats about the study: it only speaks about recurrent infections (theoretically, the treatment may be less effective in patients infected for the first time), though an accompanying editorial by the NEJM board made it clear they believe the results are transplantable to initial infections; it was unblinded, so researchers knew which group a patient was in ; it was made up of mostly elderly patients; it didn’t include sicker ICU patients. None of those limitations seem debilitating enough to cast much doubt about the results, though.
You can see why relaxing regulations on this treatment can be pretty beneficial for patients and the system as a whole: a shorter, cheaper, more effective treatment is a win-win-win for the patient, for the community (an in-demand hospital bed opens up for a patient that needs it), and for the country.
The main issue with the FDA’s announcement is that it doesn’t go far enough; theoretically, it only covers treatment for patients that didn’t respond to standard therapy (i.e., metronidazole or vancomycin/rifaximin). At the very least, it should encourage future research on fecal transplants and the microbiome more generally – not only for c. diff, but potentially for other debilitating bowel diseases such as Crohn’s and irritable bowel syndrome .
1. Let’s also back up to reiterate that I am not a doctor
2. This procedure would have been tough to double-blind, for obvious reasons.
3. Even further, actually – some research has indicated that the microbiome is important for everything from depression to obesity. For more, science reporter Carl Zimmer’s been beating the microbiome drum for some time, and this Radiolab episode about the gut touches on fascinating research