Researchers: Fecal transplants promising treatment for antibiotic-resistant bacteria

Clostridiodes difficile (C. diff) is the most common health care-acquired infection in the U.S. It affects nearly half a million patients each year and becomes a recurring infection for nearly a third of them. If untreated, C. diff can lead to sepsis and death.

A recent article in The Journal of the American Osteopathic Association examines how the bacteria functions and the treatment decisions it imposes on physicians.

“Twenty-five years ago, C. diff infections were easier to manage and often resolved with discontinuation of the initiating antibiotic,” says Robert Orenstein, DO, an infectious disease specialist at Mayo Clinic and the article’s lead author. “We’re not sure what changed, but infections have become increasingly common and pernicious.”

The standard FDA-approved treatment for C. diff is an oral course of the antibiotic vancomycin or fidaxomicin. However, antibiotic treatment of C. diff can also perpetuate the infection by killing off beneficial gut microbes.

“Think of your gut as a forest and C. diff as a weed,” says Dr. Orenstein. “In a thriving forest, weeds barely get a foothold. But if you burn the forest down, the weeds are going to flourish.”

New options often out of reach

Newer antibiotics, like fidaxomicin, that more specifically target C. diff, are now available but are often prohibitively expensive, he adds. A 10-day course of treatment with fidaxomicin can cost up to $3,000.

Transplanting human donor fecal microbiota into the colon of an affected patient may be the best treatment for those not helped by C. diff targeted antibiotics. Unlike antibiotics, which destroy both good and bad bacteria, fecal microbial transplants (FMT) help restore the structure and function of the gut.

By rapidly replenishing the gut ecosystem with a diverse group of microbes, the host may then block C. diff’s spore from germinating and propagating disease via its toxins.

Microbial transplants can be delivered by several methods, including enemas, capsules or direct instillation, to replace the diverse flora that maintain immune and metabolic function. Despite the popularity of FMT, the procedure is considered investigational and there are currently no FDA-approved fecal transplant products.

Several companies have microbial replacement products in Phase 3 clinical trials that could potentially come to market as early as 2020, Dr. Orenstein notes. For this reason, he strongly urges health care providers to refer patients with recurrent C. diff for these trials. In the meantime, the FDA enforcement discretion policy reserves fecal transplants for patients experiencing their second recurrence (third episode) of C. diff infection.

Difficult decisions

C. diff is common in health care settings. The bacteria rarely cause problems in people with healthy gut microbiota and immune systems, according to researchers. However, people who are already ill and taking antibiotics, chemotherapy, or proton pump inhibitors—which all greatly disrupt the gut ecosystem—are at risk.

This poses a problem for hospitals, which can receive lower reimbursement when C. diff infection rates rise. Physicians must make a difficult cost/benefit analysis when treating patients, especially elderly people who are particularly vulnerable to more severe outcomes.

“Due to the high cost of fidaxomicin, we aren’t supposed to prescribe it before giving vancomycin a fair shot,” says Dr. Orenstein. “But there are other costs and risks to consider that may well dwarf the initial $3,000 for fidaxomicin.”

He explains that physicians have to consider that vancomycin treatment has up to a 30 percent C. diff recurrence rate after the first course and a 40 to 60 percent recurrence rate after the second. Depending on the patient’s insurance, those prescriptions can be between $100 and $1,000 each. All the while, the patient is suffering and may require hospitalization—which has its own extensive subset of costs and risks—and is actively shedding the C. diff spores, which may infect others.

Prevention above all

Dr. Orenstein believes the newer treatment options will improve outcomes, but patients and physicians need to assume greater responsibility for prevention.

“One of the most effective things physicians can do is become more responsible with antibiotic prescriptions,” says Dr. Orenstein. “That means only prescribing when they are clearly indicated, not for colds or viral sinus infections. We also must be especially judicious with elderly patients.”