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Study Testing Repurposed Drugs with Resistant Bacteria

C. difficile bacteria

Yellow-green fluorescence of C. difficile bacteria (Centers for Disease Control and Prevention)

21 August 2017. A university team is investigating two current drug compounds for their ability to take on a new task, fighting bacteria becoming resistant to antibiotics. The five-year project led by Mohamed Seleem, a professor of microbiology at Purdue University, is funded by a $1.6 million grant from National Institute of Allergy and Infectious Diseases, part of National Institutes of Health.

Seleem and colleagues from Purdue’s veterinary medicine school in West Lafayette, Indiana are looking into expediting the search for new ways of treating three bacterial diseases becoming more resistant to existing antibiotics. One of the bacteria is Clostridium difficile or C. difficile. According to Centers for Disease Control and Prevention, almost a half-million C. difficile infections occurred in the U.S. in 2011, leading to 29,000 deaths within 30 days of diagnosis. The infections are often contracted in health care facilities, such as clinics and hospitals, causing inflammation in the colon, and symptoms including watery diarrhea, abdominal pain, nausea, loss of appetite, and fever.

Another particularly troublesome bacterium is methicillin-resistant Staphylococcus aureus or MRSA, implicated in outbreaks found both in community and health care settings, leading to sepsis, pneumonia, and bloodstream infections. CDC says MRSA infections in health care settings are declining, but remain a major threat to patients. The agency does not have data on MRSA infections acquired in community settings.

The third bacterium is vancomycin-resistant enterococcus, or VRE, also found in health care settings. Enteroccocci bacteria are often found in the intestines and the female genital tract, with many current strains now resistant to the antibiotic vancomycin, a first-line treatment for infections from this bacterium.

The Purdue team already screened some 4,000 current drugs that graduated from patent protection for potential antimicrobial activity, to find compounds that can be repurposed against these three bacteria. The main goal in this project is to short-cut the drug-development process, with compounds whose safety are proven. “It can take 15 years or longer to move a new drug through the approval pipelines,” says Seleem in a university statement. “The solution is to find drugs that we already know are safe.”

The two drugs being investigated are auranofin and ebselen. Auranofin is currently approved by FDA as a treatment for rheumatoid arthritis, while ebselen is a promising antioxidant compound, but not yet approved by FDA. The researchers say their tests in lab cultures and animals show the two compounds are superior against the three target bacteria than current antibiotics of choice.

The new project is expected to validate the team’s earlier studies of thee compounds for systemic, superficial, and intestinal infections. The researchers note that FDA granted orphan drug status to auranofin as a treatment for two other bacteria causing intestinal infections, which also validates their approach.

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