Small-Molecule Drug Disarms Deadly C. difficile Bacteria by Inactivating Its Toxins; Collateral Damage Associated with Antibiotic Treatment Is Not Seen, Stanford Study Shows

A drug that blocks the pathology of the intestinal pathogen Clostridium difficile (C. difficile) without killing resident, beneficial microbes may prove superior to antibiotics, currently the front-line treatment for the infection,according to results of a recent study by researchers at the Stanford University School of Medicine. The drug, ebselen, inactivates two toxins produced by the bacterium, halting the pathology, without killing the bacterium. By not aiming to kill the pathogen with antibiotics, scientists were able to avoid wiping out sizable numbers of beneficial gut microbes. And while their study was performed in mice, the drug used has already been tested in clinical trials to treat other, unrelated conditions. Consequently, the researchers believe it could be moved rapidly into human trials for the treatment of C. difficile, as well. The findings, published online on September 23, 2015 in Science Translational Medicine, constitute the first-ever demonstration of a small molecule’s ability to disarm C. difficile without provoking the collateral damage caused by antibiotics. The article is titled “A Small-Molecule Antivirulence Agent for Treating Clostridium difficile Infection.” C. difficile is responsible for more than 250,000 hospitalizations and 15,000 deaths per year in the United States, costing the country more than $4 billion in health-care expenses, said the study’s senior author Matthew Bogyo, Ph.D., Professor of Pathology and of Microbiology and Immunology. Lead authorship of the study is shared by Kristina Bender, Ph.D., a former postdoctoral scholar in Bogyo’s lab, and Megan Garland, a student in Stanford’s Medical Scientist Training Program. “Unlike antibiotics — which are both the front-line treatment for C.
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