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This article is from the In-Depth Report The Crisis of Antibiotic Resistance
See Inside December 2011

Swapping Germs: Should Fecal Transplants Become Routine for Debilitating Diarrhea?

A potentially beneficial but unusual treatment for serious intestinal ailments may fall victim to regulatory difficulties

The physicians performing the transplants decry the regulatory bottleneck because new treatments for C. difficile infection are critically needed. C. diff, to use the common medical shorthand, has risen in the past 30 years from a recognized but tolerated consequence of antibiotic treatment to a serious health threat. Since 2000, when a virulent new strain emerged, cases have become much more common, occurring not only in the elderly but in children, pregnant women and people with no obvious health risks. One study estimated that the number of hospitalized adults with C. diff more than doubled from about 134,000 patients in 2000 to 291,000 patients in 2005. A second study showed that the overall death rate from C. diff had jumped fourfold, from 5.7 deaths per million in the general population in 1999 to 23.7 deaths per million in 2004.

C. diff has also become harder to cure. Thanks to increasing antibiotic resistance, standard treatment now relies on two drugs: metronidazole (Flagyl) and vancomycin. Both medications are so-called broad-spectrum antibiotics, meaning that they work against a wide variety of bacteria. Thus, when they are given to kill C. diff infection, they kill most of the gut’s friendly bacteria as well. The living space that those bacteria once occupied then becomes available for any C. diff organisms that survive the drugs’ attack. As a result, roughly 20 percent of patients who have had one episode of C. diff infection will have a recurrence; 40 percent of those with one recurrence will have another; and 60 percent of those who experience a second bout are likely to suffer several more. Some victims with no other options must have their colon removed. (A new drug, fidaxomicin, which was approved for C. diff infection by the FDA in late May, may lead to fewer relapses because it is a narrow-spectrum antibiotic.)

A Simple Procedure
The details of how the transplantation of microbes eliminates C. diff infection have not been well studied, but Alex Khoruts, a gastroenterologist and immunologist at the University of Minnesota who has performed two dozen fecal transplants over the past two years, has demonstrated that the transplanted bacteria do take over the gut, replacing the absent friendly bacteria and outcompeting C. diff. In 2010 he analyzed the genetic makeup of the gut flora of a 61-year-old woman so disabled by recurrent C. diff that she was wearing diapers and was confined to a wheelchair. His results showed that before the procedure, in which the woman received a fecal sample from her husband, she harbored none of the bacteria whose presence would signal a healthy intestinal environment. After the transplant—and her complete recovery—the bacterial contents of her gut were not only normal but were identical to that of her husband.

Most clinicians who perform fecal transplants ask their patients to find their own donors and prefer that they be a child, sibling, parent or spouse. “For me, it’s aesthetic,” says Christina Surawicz, a professor of medicine at the University of Washington, who has done transplants on two dozen patients and published an account of the first 19. “There’s something very intimate about putting someone else’s stool in your colon, and you are already intimate with a spouse.”

To ensure safety, the physicians performing the procedure require that donors have no digestive diseases and put them through the same level of screening that blood donation would require. That process imposes a cost in time and logistics because standard rules for medical confidentiality require a donor to be interviewed separately from the potential recipient. It also carries inherent financial penalties. The donor’s lab work most likely will not be covered by insurance; the transplant procedure may or may not be covered by the patient’s insurance.

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