Non-antibotic drug shows promise in deadly C. difficle infections

By Julie Steenhuysen

A non-antibiotic drug already tested in people for other uses may be active in treating Clostridium difficile.

Studies in mice by researchers at Stanford University School of Medicine showed that the drug ebeselen, a compound being studied in clinical trials for a variety of other conditions, blocked infections by disabling the bacteria's toxins.

The study was published September 23 in Science Translational Medicine.

C. difficile is an antibiotic-resistant infection that can cause diarrhea, colitis, the inflammation of the colon. It infects nearly half a million people in the United States each year and contributes to 29,000 deaths.

Patients who get these infections are treated with antibiotics, which wipe out friendly bacteria and contribute to antibiotic resistance.

In the new study, led by Kristina Oresic Bender and colleagues at Stanford, the team looked for compounds that would simply keep the bacteria from making people sick, allowing normal, protective gut bacteria to remain intact.

The team searched through a federal library of compounds for drugs that targeted C. difficile's toxins.

They settled on ebselen, an antioxidant tested in late-stage trials by Daiichi Sankyo as a stroke treatment, but never reached the market and is now off patent.

In studies in mice, the compound curbed infections, including those caused by a drug-resistant strain of C. difficile, blocking both inflammation and colon damage in treated mice.

The Stanford team hopes to move the drug rapidly into clinical trials for treating C. difficile infection.

Dr. Alexander Khoruts, a C. difficile expert from the University of Minnesota who was not involved in the research, said the approach of targeting toxins instead of trying to wipe out bacteria "seems promising" in animals.

But Khoruts said many questions remain. He said studies in people need to determine the most effective dose and duration of treatment, as well as establish potential toxicity of the compound.

Several groups are working on alternatives to antibiotics for C. difficile. Last week, Merck & Co said its experimental antibody cut the risk that C. difficile infections would return. Others are working on vaccines to fight the infections.

Doctors also treat patients with "stool transplants" - inserting fecal material from a healthy person into the gut of someone with severe diarrhea to restore friendly bacteria.

SOURCE: http://bit.ly/1V9FLij

Sci Transl Med 2015.

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