Antibiotic standard treatment for C. diff, but fecal transplant also an option

TORONTO – Most people sickened by C. difficile can be successfully cured with antibiotics, but for patients who continue to suffer relapses of the debilitating and potentially deadly bowel infection, doctors sometimes turn to a last-ditch salvage therapy known as a fecal transplant.

That’s right, doctors transplant stool from a healthy donor into the intestinal tract of a patient whose colon is overrun with the bacterium Clostridium difficile. The idea is to repopulate the colon with so-called good bacteria from the donor stool in a bid to crowd out the disease-causing agent or keep it in check.

Fecal transplants aren’t new – they have been used to treat C. difficile on an ad hoc basis for about 50 years, said Dr. Susy Hota, an infectious disease specialist at the University Health Network in Toronto.

But as outbreaks of the disease continue – at least eight Ontario hospitals are now grappling with clusters of cases that have been linked to 20 deaths since late May – interest in fecal transplants has been growing, along with ways to prevent the infections from occurring in the first place.

C. difficile is widespread in the environment, with up to five per cent of the population carrying it without ill effect.

But for some patients, taking antibiotics for pneumonia or another infection can kill off the good bacteria in the colon, allowing C. difficile to proliferate. Chemotherapy for cancer or other immune-suppressing drugs can also disrupt the natural bacterial balance in the colon, letting the infection take hold. That can lead to severe diarrhea, destruction of parts of the bowel or potentially fatal blood poisoning.

A virulent epidemic strain, known as NAP-1, killed an estimated 2,000 patients in Quebec in the last 10 years, and sporadic outbreaks of the bug have caused scores of deaths at hospitals elsewhere in the country.

What makes the bacteria especially tricky is that it also produces spores that can contaminate surfaces and are difficult to eradicate with most cleaning products, making it one of the most common causes of infectious diarrhea in hospitals and long-term care homes.

Ironically, antibiotics are the standard first-line treatment for C. difficile, Hota said Friday. Metronidazole, also known as Flagel, is typically used for initial or mild episodes. For severe or recurrent infections, vancomycin in pill form is administered. Sometimes the two drugs are used in combination.

Hota said the accepted norm for dealing with any bacterial infection is to kill the organism, and it’s no different with C. difficile.

"But there’s a problem with that that we’ve always recognized, that you’re stuck in a cycle," she said. "You get C. difficile because you’ve been exposed to antibiotics for another infection and then the treatment of C. difficile is yet more antibiotics, which unfortunately do kill those other organisms around as well, so it’s harder to recover from C. difficile for that reason."

About 20 to 30 per cent of people have relapses, and the vancomycin used to treat the stubborn infection is highly expensive and usually taken for many weeks to catch both live bacteria and the bacteria-producing spores.

Despite the ick factor, a fecal transplant offers another option for patients suffering repeated bouts of the "miserable" disease, said Hota, although the treatment has not been rigorously studied and there are no standards for the procedure.

Hota is leading a randomized controlled trial to compare fecal transplants to six weeks of vancomycin in relapsing patients to see which treatment is more effective. She hopes to publish results from the study, which began last October and aims to recruit 146 patients, within two years.

About 50 grams of donated stool is mixed with saline and administered by enema, explained Hota. Donors are carefully screened for infectious diseases like HIV and hepatitis, as well as asymptomatic colonization with C. difficile.

"There’s no need for a tissue match, it’s not like an organ donation," she said. "It could be a complete stranger or somebody that you care about. The patient will identify a potential donor, often a family member, a spouse or a partner."

While researchers continue to look for more effective treatments for C. difficile – a few are in the research pipeline – others are looking for ways to prevent the infection from ever occurring.

Dr. Pierre-Jean Maziade, an infectious disease specialist at Pierre-Le-Gardeur Hospital in suburban Montreal, said doctors there began automatically prescribing a high-dose probiotic along with antibiotics after an August 2003 to February 2004 outbreak of C. difficile that was linked to the deaths of 20 elderly patients.

Following the decision to prescribe Bio-K Plus, which contains a number of "good" bacteria, cases dropped dramatically and the hospital has since recorded only two C. difficile-related deaths, he said.

A published study of the probiotic had shown it cut the risk of infection, so his hospital decided to try the product, said Maziade, who has no financial connection to the Canadian maker Bio-K Plus International Inc.

"We had to control the outbreak because we had a lot of mortality in the first six months and we can’t accept that. We wanted to try something to protect our patients."

Karen Madsen, a professor of medicine at the University of Alberta who studies probiotics, said scientific evidence is beginning to show the benefits of using various strains of probiotics to prevent C. difficile.

"I think it’s something that hospitals need to look at," Madsen said from Edmonton.

"If you take an elderly patient coming into the hospital who’s going to be on antibiotics, who is not immunocompromised, then yes, I think that population" should be given probiotics, she said. "It’s extremely low risk, it’s inexpensive and if you use the right probiotic at the right dose, there’s evidence that it significantly reduces the risk of contracting (C. difficile)."

"So it’s a no-brainer, really."