What to do about antibiotics and drug resistance? University of Illinois chemists and their collaborators have an idea…repurposing! There are drugs already approved to treat things such as parasitic infections and cancers, that—lo and behold—just may work as antibiotics agents against staph infections.
Strategy for Antibiotic Resistance: Repurposing
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The work, which was led by Eric Oldfield, Ph.D., a chemistry professor at the University of Illinois, was published in the Proceedings of the National Academy of Sciences.
According to the news release, “The researchers were interested in finding compounds that sabotage the bacteria’s energy production line, shutting down cellular processes within the bacterium. These agents, called uncouplers, are already used to treat parasitic infections. Inspired by clofazimine, a leprosy drug that is now being used to treat tuberculosis, the researchers searched among drugs that are either already available or in development to find uncouplers based on their chemical structures.” (Liz Ahlberg, December 22, 2015)
Dr. Oldfield told OTW, “It is important to understand that we are focusing on new leads having multiple mechanisms of action and that it will be challenging to optimize such compounds. Then again, Sir James Black, winner of the 1988 Nobel Prize in Physiology and Medicine, famously stated that, ‘The most fruitful basis for the discovery of a new drug is to start with an old drug.’”
“About a decade ago we discovered that some drugs like amiodarone and dronedarone (heart drugs) acted as uncouplers (as well as sterol biosynthesis inhibitors in parasitic protozoa). More recently we found that the fertility drug clomiphene was also an uncoupler and was also found to kill staph, blocking cell wall biosynthesis (like penicillin). Screening several of these sorts of drugs led us to discover numerous potential leads that work by targeting both enzymes as well as cell energetics.”
“It is possible that some of the leads might be developed to treat nosocomial staph infections (post surgery); and there are definitely new drugs needed for osteomyelitis, gunshot wounds etc.”
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Discussion
This is a fascinating development. In my practice we've seen similar outcomes with the revised protocol. The key differentiator seems to be patient selection criteria. Has anyone else noticed the correlation with BMI thresholds?
Great point. I'd push back slightly on the conclusion, the sample size in the cited study is too small to draw population-level inferences. That said, the directional signal is compelling and worth a larger RCT.
We implemented a similar approach last year. Early results are promising but we're still gathering 12-month follow-up data. Happy to share our protocol if anyone is interested.
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