Doctors Discover New Treatment for “Superbug” C. difficile

As so-called “superbug” bacteria continue to develop new ways of resisting antibiotics, scientists are on the search for new and alternative treatments. Promising news from a recent study is now showing that we may be able to battle the most virulent strains of Clostridium difficile bacteria with a class of drugs already on the market.

Marking a somewhat surprising discovery by two researchers from The Skaggs Institute for Chemical Biology and The Worm Institute of Research and Medicine at The Scripps Research Institute, a new paper published in the journal Scientific Reports details new findings on the effective use of deworming drugs on a broad range of C. difficile strains.

According to the Centers for Disease Control and Prevention (CDC), the threat of infections caused by the pathogen has reached an urgent hazard level in the United States, causing nearly 500,000 infections, 15,000 deaths, and costing $1 billion in excess medical expenses each year.

People suffering from C. difficile infections experience life-threatening diarrhea, often brought on after a hospital visit or treatment for other infections with antibiotics. The bacteria cause illness by releasing disease-inducing toxins A and B, and infections can be persistently recurring and hard to treat. Strains of the bacteria have proven resistant to antibiotic drugs such as fluoroquinolone, clindamycin, and moxifloxacin, and with some strains causing particularly deadly outbreaks in hospitals around the country, the medical community has been on the hunt for alternative treatments against C. difficile, investigating small molecule and biotherapeutic strategies.

Enter researchers Kim D. Janda, PhD, and Major Gooyit, PhD. A press release issued by The Scripps Research Institute explains how after personally dealing with a difficult infection from C. Difficile, Dr. Janda became keen on researching better drugs to fight the illness. In seeking a new weapon, the researchers made a novel discovery on the effectiveness of salicylanilide anthelmintics—a class of veterinary drugs commonly used for deworming cattle, sheep and goats—against the bacteria. They knew salicylanilides have antimicrobial properties and low oral bioavailability, and had shown promise in fighting Staphylococcus infections, and so the researchers began testing several forms of the drug.

“We started looking at other compounds for their effects on C. difficile and happened to be using a salicylanilide called closantel as a control,” said Dr. Janda, and the drug showed a surprising effectiveness.

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.