Not quite five years ago, Stephen Freeman, MD, stood in an endoscopy suite at University of Colorado Hospital, ready to perform a colonoscopy. The seemingly routine procedure was anything but.
Freeman’s patient suffered from severe intestinal problems caused by a recurring Clostridium difficile (C. diff) infection. She’d gone through multiple courses of antibiotics with only temporary relief from severe diarrhea. At her request – really a demand – Freeman had taken stool material donated by her husband, screened it for safety and prepared a liquid that he injected into her upper large intestine.
The fecal transplant aimed to restore a healthy bacterial balance in the patient’s gut, where toxin-producing C. diff bacteria had overwhelmed other flora. Within a day or two, the balance of bacterial power shifted. The “good” bacteria from the transplanted fecal material overwhelmed the C. diff, and Freeman’s patient got relief from the symptoms that had long plagued her.
Much has changed since that day. Fecal transplants – now called fecal microbiota transplants, or FMTs – are no longer unusual at UCH. The number more than quadrupled between 2012 and 2015, from 14 to 61. It is on pace to increase again in 2016. Freeman is now one of several GI specialists at UCH who perform them, and they don’t prepare their own materials. That’s now handled by OpenBiome, a non-profit stool bank in Somerville, Mass., that collects stool donations, screens them for infections, and provides hospitals with frozen preparations ready for fecal transplant.
“I’m happy not to have to prepare the solution,” Freeman acknowledged. Beyond that, he said, OpenBiome stool solutions are less expensive than those he prepared in-house – $375 compared with $1,000 to $2,000. Most importantly, the material is safe. The bank is “highly selective” in screening and maintaining a pool of donors that are the “healthiest of the healthy,” he said.
The success of FMT has helped to overcome whatever image problems the procedure may have had in the past. At UCH the FMT success rate is 93 percent for patients with recurrent or severe C. diff infections who have gone through three or more regimens of antibiotics. Colonoscopy is the most common delivery route for the material – and the most successful – but providers can also use enemas, upper GI endoscopies and gastric tubes.
Whatever the approach, FMT is a short outpatient procedure. Patients receive an anti-diarrhea medication afterward to help ensure the transplanted material stays in the colon before they leave. Most recover from the infection within two to seven days, with a few requiring two weeks, Freeman said. By comparison, the cure rate for C. diff patients who relapse at least twice after antibiotic treatment is only 20 to 30 percent, he added.
All of these factors have intensified public interest in FMT, said Dianna Webb, program director of the Digestive Health Center at UCH. “My opinion is that patients with this disease are often at the end of their rope and out of options,” she said. “They take to the Internet, do their research and come to us for this procedure.”
C. diff siege
It also points to a fact that has not changed in recent years: the damage wrought by C. diff. The American Gastroenterological Association estimates that each year C. diff strikes a half-million people in the United States alone, with 14,000 to 30,000 deaths linked to the infections.
“C. diff infections represent the biggest increase in the burden of GI disease the past few years,” said CU School of Medicine gastroenterologist Paul Menard-Katcher, MD, who performs FMTs. As with any invasive procedure, he said, FMTs carry a small risk of infection, but that pales in comparison to the “significant mortality and morbidity” of C. diff infections.
The disease also increases hospital length of stay and makes hospital readmissions more likely, contributing to $4.8 billion in increased health care costs each year, according to the Centers for Disease Control and Prevention.
Antibiotics remain an essential weapon against C. diff, but their diminishing effectiveness over time is not their only drawback. Repeated regimens of the medications increase the risk of microbes developing resistance, another major challenge for the health care system. As for cost, the least expensive antibiotic used to treat C. diff, metronidazole, is also the least effective, Freeman said. Vancoymycin and fidaxomicin produce better results, but they cost about $1,500 and $3,000, respectively, for a single 10-day regimen.
“These [severely ill] or relapsing patients are often on these expensive antibiotics for multiple courses over many weeks to months,” Freeman added.
In comparison, a colonoscopy typically runs about $2,500, including fees for both the hospital and the provider, Webb said.
Slow regulatory response
Yet despite the apparent advantages, FMT is only allowed – not approved – by the FDA to treat C. diff in patients who have relapsed after standard antibiotic treatment. The FDA considers the fecal material used in transplants a “biologic drug” and requires that patients be told that they are receiving an “investigational treatment” and give their informed consent based on that information.
In March 2016, the FDA proposed new rules that would tighten restrictions on FMT, specifically making it more difficult to use fecal material prepared by stool banks. The announcement spurred strong feedback that is likely to continue as patients suffering from prolonged bouts of watery stools and intestinal pain search for help.
Mary Roybal, 57, of Lakewood can speak to the misery inflicted by C. diff. She said she began having symptoms of an intestinal infection in 2011 after surgery to remove her gallbladder. She had severe attacks of diarrhea, but wasn’t diagnosed with C. diff until 2014 when she began kidney dialysis. Antibiotics helped for a time, but after several rounds of treatment the infection returned last April, leaving her so weak she said she had trouble walking.
In August, Roybal’s community provider referred her to UCH for an FMT, which Menard-Katcher performed. Roybal said she began feeling better only a couple of days after the procedure and her diarrhea and stomach pain cleared up in about a week.
“I can move again and do chores,” Roybal said. “It was amazing after being sick like that for so long.”
Whether FMT becomes a first-line treatment for C. diff and even other GI problems, such as irritable bowel syndrome, or faces even more scrutiny is unknown. But in Webb’s view, people like Mary Roybal offer powerful testimony.
“With the volume of C. diff cases increasing, patients are doing their own education and getting smarter about the disease,” she said. “FMT is a simple procedure and it can change lives. That’s the message.”