Multiple Recurring C. Diff. Infections on the Rise

The incidence of Clostridium difficile infections rose by 43% from 2001 to 2012, while the incidence of multiple recurring CDI rose by 189% over the same period.

Multiple recurring Clostridium difficile infections are becoming more common in the nation’s hospitals and researchers aren’t sure why.

In an analysis of a large, nationwide health insurance database, researcher’s at the University of Pennsylvania’s Perelman School of Medicine found that the annual incidence of multiple recurring C. difficile (mrCDI) increased by almost 200% from 2001 to 2012. During the same period the incidence of ordinary CDI increased by only about 40%. The study results were published this week in the Annals of Internal Medicine.

Related: C. Diff Infection Raises Hospital Costs by 40% per Case

The reasons for the sharp rise in mrCDI incidence is unknown. Researchers said the finding points to an increased burden on the healthcare system, including increased demand for new treatments for recurrent CDI. The most promising of these new treatments, fecal microbiota transplantation—the infusion of beneficial intestinal bacteria into patients to compete with C. difficile—has shown good results in small studies, but hasn’t yet been thoroughly evaluated.

“The increasing incidence of C. difficile being treated with multiple courses of antibiotics signals rising demand for fecal microbiota transplantation in the United States,” said study senior author James D. Lewis, MD, professor of gastroenterology and senior scholar in the Center for Clinical Epidemiology and Biostatistics.

Related: Intractable C. Diff Infection Linked to Multiple Care Settings

“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.”

In their analysis of CDI trends, the researchers examined records on more than 40 million patients enrolled in private health insurance plans. Cases of CDI were considered to have multiple recurrences when doctors treated them with at least three closely spaced courses of CDI antibiotics.

According to the analysis, the incidence of CDI rose by 43% percent from 2001 to 2012, while the incidence of mrCDI rose by 189% over the same period.

Compared to CDI patients whose infections cleared up after just one or two courses of therapy, patients with mrCDI were older (median age 56 vs. 49), more likely to be female (64% vs. 59%), and more likely to have been exposed, before their CDI, to medications such as corticosteroids, proton-pump inhibitors, and antibiotics, the researchers found.

Related: The Infection-Busting Treatment Payers Don't Want to Talk About

The rapid rise in the incidence of mrCDI may be due in part to Americans’ increasing use of such drugs. However, according to Lewis, it is likely that other causes are also involved.

“An additional driver of this rise in incidence 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,” he said.

C. difficile can encapsulate itself within hardy spores, making it relatively resistant to normal sterilizing procedures. It is notorious for spreading among vulnerable patients within hospitals. Infection causes diarrhea and severe gut inflammation, and can lead to sepsis, especially among the elderly.

The antibiotics metronidazole, vancomycin, and fidoxamicin are commonly used to treat CDI, but recurrence after initial treatment happens in roughly a third of cases.

Because C. difficile appears to thrive in people whose normal, healthy gut bacteria have been killed off or diminished, gastroenterologists recently have begun using fecal microbiota transplantation (FMT) as an alternative to antibiotics for recurrent CDI. Long used in veterinary medicine, FMT involves infusions of fecal matter from healthy intestines. The aim is to help restore a normal gut bacteria population in the patient.

A small study in 2013 found that a single FMT infusion cleared up C. difficile diarrhea in 81% of the recurrent-CDI patients who received it, whereas a standard treatment with the antibiotic vancomycin worked for just 31% of patients. Lewis said more needs to be known about FMT’s long-term safety.

The American Gastroenterological Association recently set up a formal registry for doctors to report their results with FMT procedures. “It’s a way in which practitioners who are performing fecal microbiota transplantation can contribute data to help answer these critical questions,” Lewis said.