Nearly half a million Americans get infected in a single year by Clostridium difficile, a dangerous bacteria that causes life-threatening diarrhea. It kills 15,000 people a year. It's the most common cause of health-care associated infections in U.S. hospitals.
Now researchers from Stanford say they have found a way to disarm a C. diff toxin that makes people sick, but in a way that doesn't harm those good gut microbes. The study uses a drug-like molecule called ebselen. The study was done in mice, but researchers say it could be moved quickly into human trials because ebselen is already being tested in clinical trials to treat other, unrelated conditions.
The study was published online Wednesday in Science Translational Medicine.
"This allows you to treat the symptoms without using a broad spectrum antibiotic that also kills off the good bacteria in the gut," said the study's senior author, Matthew Bogyo, a professor of pathology and of microbiology and immunology at Stanford University's School of Medicine.
Experts say the findings add to several encouraging approaches to fighting an infection that recurs in 1 out of every 5 patients who get it, according to the Centers for Disease Control and Prevention.
An experimental antibody developed by Merck was shown to significantly reduce the recurrence of C. diff infections, according to results presented by the company at a recent medical meeting in San Diego. Sanofi Pasteur is also developing a vaccine that directs the immune system to produce antibodies against C. diff toxins. Another study has shown that giving a nontoxic strain of C. diff appears to protect against recurrence of infection.
Current treatments for C. diff infections include stopping antibiotics, using appropriate antibiotics, and fecal transplants, in which the bacteria from a healthy gut are implanted into an unhealthy one.
Bogyo and others used a compound called ebselen to target a toxin produced by C. diff. Ebselen is already being used in clinical trials for chemotherapy-related hearing loss and stroke; preclinical testing shows it is safe and tolerable, he said.
Researchers treated the mice with multiple rounds of antibiotics, then introduced a virulent, multi-drug-resistant strain of C. diff. Then they gave the mice oral doses of ebselen. They found a nearly complete block of inflammation and damage to colon tissue as a result of the ebselen treatment.
Bogyo said ebselen disables the toxin's "on switch." He said the molecule is not expensive to make, and hopes researchers can move rapidly into clinical trials for treating C. diff infections.
L. Clifford McDonald, a medical epidemiologist and the CDC's leading C. diff expert, said the targeted approaches to disable the C. diff toxin are important because "the toxin is the way you develop this disease."
McDonald, who is not involved in the ebselen study, said it "looks very promising and interesting," but added that more needs to be known about ebselen in humans.