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Key findings

From fourth-century soup to 21st-century procedure, fecal transplantation proves its worth against stubborn bacteria

January 28, 2015

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VA's Dr. Dimitri Drekonja and colleagues have conducted a review of the evidence for fecal transplants as a therapy to combat C. difficile infections. (Photo by April Eiler)

VA's Dr. Dimitri Drekonja and colleagues have conducted a review of the evidence for fecal transplants as a therapy to combat C. difficile infections. (Photo by April Eiler)

Not all bacteria are bad.

Just ask the fourth-century Chinese medical doctor Ge Hong. More than 1,700 years ago, Hong put ink to paper to document a rather unique recipe for treating diarrhea— yellow soup. It was, as one might expect, not a pleasant dish but rather a broth involving dried or fermented stool from a healthy person. Taken by mouth, the bacteria in the stool would then inhabit the gut of the sick person, and bring about a cure.

Medical scholars can debate whether Ge Hong's yellow soup was the first effort at what is now called fecal microbiota transplantation. In any case, history is replete with documented examples of the practice, from Renaissance-era veterinarians to a 1958 Colorado case involving four critically ill patients.

Now an increase in a hard-to-beat intestinal bacterium has prompted VA researchers to revisit the effectiveness of FMT—a modern version of Hong's yellow soup.

Systematic review of evidence

Investigators with VA's Evidence-based Synthesis Program conducted a systematic review of the evidence surrounding FMT, in part to help VA determine if the treatment was effective enough to be offered at VA facilities. By and large, the data are promising. The researchers are preparing the results for publication.

The treatment revolves around intestinal flora. In a healthy person, the bowels are chock-full of healthy bacteria. When a person is on antibiotics, the balance can be upset; after all, antibiotics kill bacteria indiscriminately, whether harmful or not. The result, all too often, is the development of gastrointestinal disease, specifically, Clostridium difficile-related diarrhea and colitis.

"Historically C. difficile was seen mostly in those with health care exposure, almost exclusively those who have received antibiotics," says Dr. Dimitri Drekonja, a staff physician in the infectious disease section at the Minneapolis VA Health Care System. "Lately, though, there have been increasing reports of people getting it who don't have any of that exposure. We're very good at spreading germs around. MRSA used to be a bacterium that was only hospital-acquired, and it seems that C. difficile is doing the same thing, emerging from the hospital setting and moving out into the community. It is, right now, the most common cause of infectious diarrhea."

A new weapon against an urgent threat

The issue is so pressing, in fact, that in 2013, the Centers for Disease Control and Prevention placed C. difficile into its top threat category: urgent. Infection can result in repeated hospitalizations, malnourishment, and dehydration, and it can occasionally prove fatal. According to Drekonja, who is also an assistant professor of medicine at the University of Minnesota, it's not that C. difficile is hard to treat, but rather that it has a distressingly high recurrence rate. Put simply, it is one stubborn bug. Between 15 and 30 percent of patients experience recurrent episodes of the illness. It is quickly replacing MRSA as the most common bacterial infection found in hospital settings.

"The single biggest trigger is receipt of further antibiotics," says Drekonja. "But sometimes that's not modifiable. If you need antibiotics for something very serious like a severe necrotizing skin condition or a bad cellulitis, then nothing else will work. That puts you in an uncomfortable position of knowing you need treatment, but you're definitely increasing your risk of a C. difficile recurrence."

Mainstream medical treatment involves therapy with vancomycin or other antibiotics active against C. difficile and, as expected, a break from antibiotics whenever possible. These treatments, however, tend to produce sustained success only 30 to 80 percent of the time. The variation, says Drekonja, depends on the number of recurrences, duration of treatment, and other variables.

Procedure in use in VA on case-by-case basis

Currently FMT is used only on a case-by-case basis in VA, mostly through coordination with non-VA providers. "It's in an uncertain regulatory environment," says Drekonja. "Is this a drug? If so, it's not FDA-approved. Different facilities are approaching it differently."

The studies Drekonja's group reviewed focused primarily on recurring cases of C.difficile, as well as non-responsive, or refractory, cases.

"The treatment isn't usually given to acutely ill patients," says Drekonja. "The bulk of the patients had an episode or multiple episodes and were treated through conventional means. Then once they were largely asymptomatic but at risk of a recurrence, they were given the FMT."

The transplants were delivered in different ways: Some were given through the upper gastrointestinal tract, through the use of either a nasogastric or nasojejunal tube, more colloquially known as a feeding tube, or, in one study, by ingestion of capsules of frozen stool. Others were delivered via enema, rectal tube, or colonoscopy.

Positive results overall

Results overall were positive. In the frozen-capsule study, 20 patients took 15 capsules per day over two days and had a 70 percent success rate. In a study using nasogastric tubes, 81 percent of patients achieved resolution within the first three months, compared with 31 percent and 23 percent in the two control groups receiving vancomycin.

Across the board, in fact, FMT proved highly effective, with no delivery method being clearly superior to the others. Nevertheless, without confirmation from a controlled trial, Drekonja doesn't believe the procedure is ready for widespread VA use. "At this point, the evidence is largely through case series," he says.

More research is needed, and perhaps a little socialization. After all, the concept itself can be a bit distressing. Drekonja says convincing patients of the need for FMT can sometimes be a challenge.

"Those that go through it are quite satisfied. But when we have approached patients about this, a few didn't even want to finish the conversation, let alone do it. There is a certain yuck factor that will always turn off a segment of the population. Now, if they have five recurrent episodes of C. difficile, will that yuck factor all of a sudden drop out?

After all, as unpleasant as a colonoscopy, nasogastric tube, or frozen stool capsule might be— they've got to be better than Dr. Hong's yellow soup.




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