Non-antibiotic drug holds promise for fighting superbug
A new mouse study suggests that a drug with a known safety record in humans might be a new weapon in the fight against the potentially deadly intestinal infection known as C. difficile.
The drug is called ebselen, and it was well-tolerated in humans when tested as a possible treatment in a variety of clinical trials, including for stroke and bipolar disorder. Although ebselen has never been approved as a treatment for any condition in humans, the current research team thought the drug might help prevent the spread of infection in people with C. difficile.
When the researchers gave ebselen to infected mice, the drug appeared to knock out the toxic activity of C. difficile without inflicting the collateral damage on good bacteria that's normally associated with antibiotic treatment, the study reported.
The results were "very encouraging," said study senior author Matthew Bogyo, a professor of pathology and of microbiology and immunology in the department of pathology at Stanford University's School of Medicine. "Specifically, we find that oral [ebselen] dosing of mice infected with C. difficile resulted in nearly complete blockage of the damage to gut tissues that cause the symptoms in humans," Bogyo said.
It's important to remember, however, that research done in animals doesn't always turn out the same in humans. So, right now, it's unknown whether ebselen would be effective or safe in treating people with C. difficile.
The study, which was funded by the U.S. National Institutes of Health, was published in the Sept. 23 online issue of Science Translational Medicine.
C. difficile -- or Clostridium difficile -- is a bacterial infection that targets the intestine causing watery diarrhea, fever, loss of appetite, nausea and abdominal pain. This pathogen caused an estimated 500,000 hospitalizations and 29,000 deaths in the United States in 2011, according to the U.S. Centers for Disease Control and Prevention.
Currently, the infection is treated with specific antibiotics. But antibiotics kill "both the 'bad' pathogenic bacteria as well as the 'good' native gut bacteria that help to keep us healthy," Bogyo said.
The result is a weakened gut environment that puts the general population at a higher risk for getting C. difficile in the first place, while undermining the effectiveness of antibiotic treatment once an infection takes hold, he explained.
"This is why people who get C. difficile tend to relapse and get it again and again," Bogyo said.
Fecal transplantation, in which good bacteria is harvested from a healthy patient and placed inside a sick patient's gut, is one non-antibiotic treatment. However, Bogyo cautioned that the long-term ramification of this process remains unclear.
So, Bogyo and his colleagues turned to ebselen, a non-antibiotic compound designed to block the toxic activity of C. difficile, without actually killing it altogether.
The study involved a number of rounds of laboratory and animal testing, with focus centering on ebselen's impact on the activity of "Toxin B." Toxin B is C. difficile's main toxin.
Mice injected with ebselen-treated Toxin B molecules survived. Mice exposed to untreated molecules died within two days, according to the report.
Similarly, the researchers found that when mice with an antibiotic-resistant strain of C. difficile were treated with oral doses of ebselen, they experienced almost no cell damage.
"While we can only know how effective the strategy will be in humans once we start a clinical trial, we feel that our results strongly suggest that the drug will be effective, and should help to treat symptoms while allowing the good bacteria to return and control the infection," Bogyo said.
Philip Tierno, a professor of microbiology and pathology with the NYU School of Medicine at NYU Langone Medical Center in New York City, described the findings as "very important."
"It's not a new concept," Tierno said. "The notion that one could attack the infectious process by focusing on a bacteria's virulence, rather than on killing it off, dates back many decades," he explained.
"But it's taken us 70 or so years of antibiotic overuse and resistance for us to finally realize that the paradigm has to change. That you can achieve effective control of an infection by using blocking agents that neutralize the toxic aspect of bacteria, without actually having to kill it and all the healthy flora around it. And the use of this drug for this infection seems to do just that," Tierno added.
"Of course this was done in a mouse model," he cautioned. "So you have to wait until you complete trials in humans. But cells are cells and bacteria are bacteria, so if we can affect the same mechanism in our body, this should work."