A drug approved to fight tapeworms in people may also be a powerful way to treat MRSA infections, which kill thousands of people a year in the United States alone.
A new study shows that niclosamide, which is on the World Health Organization’s list of essential medicines, suppressed the growth of dozens of methicillin-resistant Staphylococcus aureus (MRSA) cultures in lab dishes and preserved the lives of infected nematode worms.
In these tests, both niclosamide and a closely related veterinary parasite drug, oxyclozanide, proved to be as effective (at lower concentrations) as the current last-resort clinical treatment, vancomycin.
The drugs both belong to a family of medicines called salicylanilide anthelmintics and have both also trounced another “gram positive” pathogen, Enterococcus faecium, in lab tests.
Why these 2 drugs?
“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,” writes lead author Rajmohan Rajamuthiah, a postdoctoral scholar in the Warren Alpert Medical School at Brown University.
Last year the team reported that after screening more than 600 drugs against infected nematode worms, the salicylanilide anthelmintic drug closantel appeared to be protective for the worms. That led to the new research, where they tested niclosamide and oxyclozanide.
In their experiments, reported in the journal PLOS ONE, even low concentrations of the drugs allowed more than 90 percent of MRSA-infected worms to survive, compared to less than 20 percent survival among controls. In the petri dishes the drugs cleared gaping zones of growth inhibition in MRSA culture spread over the plate, while a control substance did nothing.
Between the two, oxyclozanide proved to be a more effective MRSA killer, while niclosamide effectively suppressed MRSA growth but did not completely eradicate the bacteria. Although niclosamide proved to be “bacteriostatic” instead of “bactericidal” like oxyclozanide, it may still pack plenty of punch to keep MRSA in check and give the body’s immune system the upper hand, Rajamuthiah says.
Petri dishes aren’t people
The researchers tested the effects of the drugs on mammalian cells, including sheep red blood cells (which fared just fine) and cancerous human liver cells (which happen to be easier to use than healthy liver cells). Niclosamide proved to be significantly toxic against the cancer cells, which other studies had shown before.
The team also tested a hypothesis about how the drugs attack the bacteria. As they suspected, oxyclozanide appeared to work by disrupting the bacterial cell’s membranes, but there was no sign that niclosamide worked the same way.
Petri dishes and worms aren’t substitutes for people, and some issues need further investigation, the researchers say. For example, people have been shown to clear niclosamide out of their systems quickly, and the drug does a poor job of working its way out of the bloodstream and deep into tissues.
Will it be toxic?
But there may also be an upside to the rapid clearance, Rajamuthiah says. That might limit the toxicity of the drug, and until it is tested, it’s not clear that quick clearance would undermine the drug’s performance against MRSA.
“Remember that no one has ever tested niclosamide for treating bacterial infections,” he says.
If niclosamide, which is already used in humans for one purpose, can also help them fight off a superbug, or if it’s apparently more effective and less toxic cousin oxyclozanide can gain approval for human use, doctors could obtain much needed ammunition against MRSA.
“The relatively mild toxicity of oxyclozanide is encouraging based on in vitro tests,” Rajamuthiah says. “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.”
Particularly important is that because oxyclozanide attacks the cell membrane instead of metabolic pathways, it may be more difficult for MRSA to develop resistance, Rajamuthiah says.
The National Institutes of Health funded the work.
Source: Brown University