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Tape Worm Drug Shows Promise Against MRSA ‘Superbug’

Niclosamide as effective as vancomycin in early investigation

A new study provides evidence from lab experiments that a drug already used in people to fight tapeworms might also prove effective against strains of the “superbug” methicilin-resistant Staphylococcus aureus (MRSA), which kills thousands of people a year in the U.S.

The paper, published in PloS One, showed that niclosamide, which is on the World Health Organization’s list of essential medicines, suppressed the growth of dozens of MRSA cultures in lab dishes and preserved the lives of nematode worms infected with the bug. 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 medications called salicylanilide anthelmintics, and they both also trounced another Gram-positive pathogen, Enterococcus faecium, in lab tests.

“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,” wrote lead author Dr. Rajmohan Rajamuthiah.

Last year, the team reported that after screening more than 600 drugs against infected nematode worms, it had found that the salicylanilide anthelmintic agent closantel appeared to be protective for the worms. That led to the new research, in which the scientists tested niclosamide and oxyclozanide.

In their experiments, even low concentrations of the drugs allowed more than 90% of MRSA-infected worms to survive compared with a survival rate of less than 20% among controls. In petri dishes, the drugs cleared gaping zones of growth inhibition in MRSA culture spread over the plate, the authors said, whereas a control substance did nothing.

Between the two agents, oxyclozanide proved to be a more-effective MRSA killer, wheras 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 enough punch to keep MRSA in check and give the body’s immune system the upper hand, Rajamuthiah said.

The researchers tested the effects of the drugs on mammalian cells, including sheep red blood cells and cancerous human liver cells. Niclosamide proved to be significantly toxic against the cancer cells, but the drug is already approved for human use.

The team also tested a hypothesis about how the drugs attack MRSA. As they suspected, oxyclozanide appeared to work by disrupting the bacterial cells’ membranes, but there was no sign that niclosamide worked the same way.

The researchers acknowledge that petri dishes and worms are not substitutes for people, and that some issues need further investigation. 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.

“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,” they wrote. “Further studies should include the evaluation of these compounds in systemic and localized infection models in rodents.”

“The relatively mild toxicity of oxyclozanide is encouraging based on in vitro tests,” Rajamuthiah said. “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.”

Because oxyclozanide attacks cell membranes instead of metabolic pathways, it might be more difficult for MRSA to develop resistance to it, Rajamuthiah added.

Sources: Brown University; April 23, 2015; and PLoS One; April 21, 2015.

 

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