The study, published in PLOS ONE, demonstrates that the drug niclosamide can suppress the growth of methicillin-resistant Staphylococcus aureus ( MRSA) cultures in both laboratory dishes and infected nematode worms.
A veterinary parasite drug called oxyclozanide was also found to be effective. Both drugs are part of a larger family of medicines known as salicylanilide anthelmintics and worked well in tests against another pathogen called Enterococcus faecium.
"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," explains lead author Rajmohan Rajamuthiah, from Brown University and Rhode Island Hospital.
MRSA was associated with 80,461 life-threatening infections in the US in 2011, resulting in 11,285 fatalities. The bacteria's resistance to traditional antibiotics is driving a need for new
treatment strategies and forms of anti-infective medication.
Previous research from Rajamuthiah and his team testing over 600 different drugs found that another salicylanilide
anthelmintic drug - closantel - was protective for nematode
worms that were infected with MRSA. This finding led the team to test niclosamide and oxyclozanide.
In the new study, both drugs left large areas of growth
inhibition in petri dishes containing MRSA cultures. More than 90% of nematode worms infected with MRSA survived after receiving even low concentrations of each drug.
Oxyclozanide was more effective at killing MRSA than niclosamide, which was more bacteriostatic (good at
suppressing bacterial growth) than bactericidal. However,
Rajamuthiah believes that this may still be enough to control
the spread of MRSA infection, giving the immune system time
to deal with the infection itself.
Further studies required due to 'low level of systemic circulation'
The drugs were also tested on the red blood cells of sheep and
cancerous human liver cells. The sheep cells were unaffected by either drug, whereas the researchers found that niclosamide was toxic to the cancer cells.
Although other studies have previously demonstrated the
toxicity of niclosamide, the drug has already been approved for use in humans by the US Food and Drug Administration (FDA).
There are a number of problems that the researchers will need
to investigate further. Niclosamide is known to clear out of people's system quickly and is inefficient when it comes to moving from the bloodstream and deep into tissues where
infection may 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," suggest the authors of the study.
There are also limitations to what can be found by only testing the drugs on cultures in petri dishes and nematode worms.
"Further studies should include the evaluation of these
compounds in systemic and localized infection models in
rodents," write the authors, and rodent experiments are
currently being planned.
However, Rajamuthiah suggests that the manner in which
niclosamide leaves the body quickly is not necessarily a bad
thing, as it may limit the toxicity of the drug. Additionally, it is unknown whether quick clearance would reduce the drug's
effectiveness in treating MRSA.
The researchers also discovered that oxyclozanide attacks
bacteria by disrupting their cellular membranes. By attacking these instead of their metabolic pathways, Rajamuthiah suggests it may be more difficult for the
bacteria to become resistant to the drug.
If further testing - and approval for human use in the case of oxyclozanide - proves successful, the two drugs could present clinicians with useful new options in their battle with this infection.
"The relatively mild toxicity of oxyclozanide is encouraging
based on in vitro tests," Rajamuthiah concludes. "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."
Recently, Medical News Today reported on a study in which
researchers identify a dosing strategy that could revive first-line antibiotics and preserve last-resort antibiotics in the fight against drug-resistant bacteria.
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