Researchers have discovered that a drug currently used to treat people with tapeworms may have the potential to be used to fight the notorious MRSA bacteria as well.
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.
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.