Researchers found certain forms of deworming medications were able to halt C. difficile growth.
In the journal Scientific Reports, researchers from The Scripps Research Institute (TSRI) in San Diego, CA, reveal that some forms of the deworming medications salicylanilides stopped the growth of numerous C. difficile strains - even some that cause recurrent infections.
According to a 2015 study from the Centers for Disease Control and Prevention (CDC), C. difficile is estimated to have caused almost half a million infections in a single year in the United States, and around 29,000 patients died from the infection within 30 days of diagnosis.
For primary C. difficile infection, antibiotic treatment is often the first port of call. But the CDC note that infection returns for around 20 percent of patients, due to the emergence of what are called "hypervirulent" strains.
Making treatment of C. difficile infection even more challenging is that an increasing number of strains are developing antibiotic resistance; the situation has become so serious that the CDC deem C. difficile as an "urgent threat" to public health.
Now, senior author Kim D. Janda - director of the Worm Institute for Research & Medicine (WIRM) and the Ely R. Callaway, Jr. professor of chemistry at TSRI - and team suggest salicylanilides may be a feasible treatment for C. difficile infection.
Salicylanilides halted C. difficile growth
Spurred by his own experience of hard-to-treat C. difficile infection, Janda - alongside first author Major Gooyit, a research associate in Janda's lab - began testing a number of compounds for their effects on C. difficile.
By doing so, they found that a salicylanilide called closantel - used to treat worms in cattle, sheep, and goats - showed some effectiveness in halting growth of the bacterium.
On testing a further three salicylanilides on various lab-cultured C. difficile strains - rafoxanide, niclosamide, and oxyclozanide - they saw the same effect.
These deworming medications even stopped the growth of a C. difficile strain called BI/NAP1/027 - a strain known to be hypervirulent - and they were just as effective as antibiotics currently used to fight this strain, and even more effective in some cases.
Further testing revealed that closantel and rafoxanide were best for halting C. difficile growth, and they even demonstrated some effectiveness against deadly "stationary-phase" C. difficile cells.
Stationary-phase cells produce the toxins that trigger inflammation of the colon in C. difficile infection. In hypervirulent strains of the bacterium, these cells can be so active that they lead to patient death.
What is more, stationary-phase cells produce the bacterial C. difficile "spores" that persist on toilets, washbasins, and other surfaces, contributing to high transmission rates in healthcare settings.
Drugs could be quickly repurposed to treat C. difficile
While the researchers are unable to explain precisely how salicylanilides halt C. difficile growth, they point to previous research that suggests the compounds modify the electrical properties of bacterial cell membranes, which can hinder their survival.
With this in mind, Janda and Gooyit created new salicylanilide compounds, incorporating structures that boost their cell membrane-altering effects. This, they found, increased their growth-halting effects against C. difficile, even in strains with stationary-phase cells.
Additionally, the researchers found that the new compounds appeared to have little impact on beneficial gut bacteria, and C. difficile showed no signs of evolving to develop resistance to the drugs.
According to the team, one additional benefit of salicylanilides for C. difficile infection is that in pill form, they take a long time to be absorbed into the bloodstream. This means they reside in the gut, where they are needed to fight infection.
The researchers say they are now testing the newly developed salicylanilide compounds in animal models of C. difficile, and they are already in the process of negotiations to license salicylanilides for further development as a treatment for the infection.
"These salicylanilide compounds have all the right features, and they've long been used in animals, so I think they can be quickly repurposed against C. difficile infections in people."
Kim D. Janda