Recurrent C. difficile Incidence is Rapidly Increasing, Underscoring Need For New Therapies

New research from the Perelman School of Medicine at the University of Pennsylvania (UPenn) presents startling new evidence on the most frequent healthcare-associated infection in the United States: Clostridium difficile.

The findings in question?

Incidence of “the most difficult of C. difficile cases,” multiple-recurring C. difficile infections (mrCDI), is rapidly increasing, thus, underscoring the need for new, effective therapies. This is according to the UPenn study, which was recently published in the journal Annals of Internal Medicine.

C. difficile is capable of being “relatively resistant to normal sterilizing procedures,” because it tends to encapsulate itself within “hardy spores.” Although there are antibiotics currently available to treat these infections—metronidazole, vancomycin, fidoxamicin—about one third of individuals who are infected experience recurrence of infection after initial treatment.

In their study, the UPenn researchers analyzed the records of “a large, nationwide health insurance database,” consisting of over 40 million US patients, to examine CDI trends. They found that, between 2001 and 2012, mrCDI incidence “per 1000 persons-years” increased by 188.8% (from 0.0107 to 0.0309 cases). The researchers considered C. difficile cases to be mrCDI if “doctors treated [the patients] with at least 3 closely-spaced courses of CDI antibiotics.” In that same time period, they found that C. difficile infections (CDI) also increased—but only by 42.7% (from 0.4408 to 0.6289 cases).

Furthermore, the researchers noted differences between mrCDI patients and regular CDI patients, “whose infections cleared up after just 1 or 2 courses of therapy,” according to the press release. Firstly, mrCDI patients were older, with a median age of 56 compared with their CDI counterparts whose median age was 49; a total of 63.8% of mrCDI patients were female, compared with 58.7% of CDI patients; and mrCDI patients had an increased likelihood of having been previously exposed to “medications such as corticosteroids (18.3% vs. 13.7%), proton-pump inhibitors (24.6% vs. 18.2%), and antibiotics (72.3% vs. 58.8%),” within 90 days of CDI diagnosis, the researchers wrote.

Although they admitted that the reason for the increasing number of mrCDI cases is currently unknown, study author James D. Lewis, MD, MSCE, professor of Gastroenterology and senior scholar in the Center for Clinical Epidemiology and Biostatistics surmises it, “could be the recent emergence of new strains of C. difficile, such as NAP1, which has been shown to be a risk factor for recurrent CDI,” according to a quote by the professor in the press release.

Regardless of why the number of cases is growing, the fact remains that it’s a serious issue. Every year, half a million Americans suffer from CDI, and these infections result in tens of thousands of deaths. Not only that, but the financial burden on the nation’s healthcare system is estimated to be about $5 billion, according to the press release. The researches feel that this substantial burden underscores the need for new treatments against mrCDI. One such treatment that they feel may hold promise is fecal microbiota transplantation (FMT).

“The increasing incidence of C. difficile being treated with multiple courses of antibiotics signals rising demand for fecal microbiota transplantation in the United States,” Dr. Lewis said in the press release. “While we know that fecal microbiota transplantation is generally safe and effective in the short term, we need to establish the long-term safety of this procedure.”

Due to the fact that C. difficile “appears to thrive in people whose normal, healthy gut bacteria have been killed off or diminished,” gastroenterologists have started using FMT as an alternative to antibiotics for treating mrCDI patients. FMT involves extracting healthy bacteria from another individual’s fecal matter, and then processing and directly transferring that bacteria to the infected patient. According to the press release, “the aim is to help restore a normal gut bacteria population in the patient and thereby discourage C. difficile growth.”

The treatment has produced positive results in some patients and indeed, a smaller study conducted in 2013 highlighted that FMT may be a strong treatment option for those with mrCDI. The researchers in that study found that 1 FMT infusion “cleared up C. difficile diarrhea” in 81% of mrCDI; vancomycin, the standard treatment, cleared up the infection in only 31% of patients. Although the results of the 2013 study seem promising, Dr. Lewis stresses that researchers still need more information pertaining to long-term safety of this treatment option.

One initiative that may help in this regard is a formal registry that has recently been created by The American Gastroenterological Association. Through this registry, doctors can report the results of FMT procedures. “It’s a way in which practitioners who are performing fecal microbiota transplantation can contribute data to help answer these critical questions,” Dr. Lewis concluded in the press release.

As C. difficile rates continue to rise, researchers are looking for better ways to treat those who are infected. With the help of this registry, researchers hope to yield more information on FMT procedures in hopes that they could be used more as a means to cut down on incidence.