With the ever persistent threat of bacterial drug-resistance looming like a carrion bird waiting for a meal, scientists are continually on the hunt for new therapeutics to thwart infections like those caused by methicillin-resistant Staphylococcus aureus (MRSA). Fortuitously, scientists from Brown University have come across two drug compounds that are already in use to treat human tapeworm infections, which they report in a new study show great promise in stopping MRSA infections.
The findings from this study were published recently in PLOS ONE under an article entitled “Repurposing Salicylanilide Anthelmintic Drugs to Combat Drug Resistant Staphylococcus aureus.”
The Brown researchers screened over 600 drugs for effectiveness against MRSA, using an in vivo assay that cultures live nematode worms infected with the drug-resistant bacteria. The investigators found two compounds niclosamide, which is on World Health Organization's list of essential medicines, and oxyclozanide, a closely related veterinary drug, were effective at suppressing MRSA cultures. Moreover, both drugs were observed to be as effective as the current last-line clinical treatment, vancomycin.
“Since niclosamide is FDA approved and all of the salicylanilide anthelmintic drugs are already out of patent, they are attractive candidates for drug repurposing and warrant further clinical investigation for treating staphylococcal infections,” explained Rajmohan Rajamuthiah, Ph.D. a postdoctoral scholar in the Warren Alpert Medical School of Brown University and first author on the current study.
Dr. Rajamuthiah and his colleagues found that oxyclozanide was more effective at killing MRSA, while niclosamide was more bacteriostatic—effectively suppressing, but not completely eradicating the bacteria. However, the researchers speculate that niclosamide may still provide enough of a kick to keep MRSA at bay while the immune system gets up to speed handling the infection.
While results from the current study are very encouraging and have Dr. Rajamuthiah and his colleagues feeling optimistic, the researchers did point out a caveat that the feel warrants further analysis. Drugs such as oxyclozanide and niclosamide are rapidly cleared by the body and are less effective at diffusing out of the bloodstream and into peripheral tissues, where some MRSA infections could reside.
“The low level of systemic circulation coupled with the rapid elimination profile of niclosamide suggests the necessity for further testing of the potential of niclosamide and oxyclozanide for treating systemic infections,” wrote the scientists. “Further studies should include the evaluation of these compounds in systemic and localized infection models in rodents.”
However, the flipside of the rapid clearance scenario is that drugs may impart very limited toxicity to patients. In order to determine the actual effects of these drugs in mammals, the researchers have planned a series of experiments in rodents to determine the two compounds efficacy and overall toxicity, when used to treat MRSA infections.
“The relatively mild toxicity of oxyclozanide is encouraging based on in vitro tests,” stated Dr. Rajamuthiah. “Since it has never been tested in humans and since it belongs to the same structural family as niclosamide, our findings give strong impetus to using oxyclozanide for further investigations.”