Examining 16 isolates of C. difficile
for in vitro susceptibilities to the salicylanilides closantel, rafoxanide, niclosamide, and oxyclozanide, the researchers found they displayed broad activity against the pathogen. The strategy was to target the vulnerability of the membrane of C. difficile
, an approach taking into account the importance of the microbial membrane in both metabolizing and non-growing cells and the associated cellular effects that could limit the likelihood of bacteria to develop resistance, as membrane-active compounds have a low propensity for resistance. They found that closantel adequately penetrated the target site; the active drug achieves therapeutic levels in the colon to repress or eliminate the outgrowth of toxigenic C. difficile
rather than activating orally.
“We show that the salicylanilide derivatives efficiently inhibited the growth of C. difficile
via membrane depolarization, and more importantly, killed both logarithmic- and stationary-phase cells in a concentration-dependent manner,” explain the authors. “The bactericidal property against stationary-phase C. difficile
could in principle lower the production of toxins and spores, which may in turn lead to improved response and mitigate CDI recurrence.”
With their findings, the researchers say they have developed new salicylanilides with improved anti-C. difficile
properties and plan to license one of these compounds to a pharmaceutical company for further development into a new drug.
While novel treatments are in development and can take time to reach the market, the CDC offers a prevention toolkit
and recommends the following measures to reduce the chance of transmitting C. difficile
, especially in healthcare settings:
- Perform hand hygiene using an alcohol-based hand rub or soap and water.
- If your institution experiences an outbreak, consider using only soap and water for hand hygiene when caring for patients with C. difficile infection; alcohol-based hand rubs may not be as effective against spore-forming bacteria.
- Environmental cleaning and disinfection strategies.
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