Researchers have developed a new drug to fight one of the deadliest infections: Clostridium difficile.
It didn't kill the bacteria and that's a good thing, the researchers report. It’s not an antibiotic. Instead, it interferes with the toxic compounds made by the bug.
A new drug to fight C. difficile is badly needed. C. difficile infections kill 29,000 Americans a year and make 450,000 sick.
Right now, antibiotics can make patients even sicker because they kill not only the C. difficile, but so-called good bacteria that keep things in balance. Once they’re killed off, “C. diff,” as it’s commonly known, can come back and even proliferate — without competition.
But this new drug interferes with a toxin that C. diff makes.
“Unlike antibiotics — which are both the front-line treatment for C. difficile infection and, paradoxically, possibly its chief cause — the drug didn’t kill the bacteria,” said Matthew Bogyo, a professor of pathology and of microbiology and immunology at Stanford University who helped lead the study.
“We figured that a molecule that interfered with the pathogen’s virulence could prevent inflammation and the disruption of colon tissue without making the intestinal environment inhospitable to normal, beneficial bacteria the way antibiotics do,” said Bogyo. That would lay the groundwork for the “good guys” to make a comeback.
The team at Stanford University screened compounds, looking for something that already exists that could be expected to fit into the physical structure of C. diff’s main toxin and inactivate it.
They found 44 different compounds and one, of them, called ebselen, has already been tested in people.
“This compound is currently in phase 2 clinical trials for the treatment of chemotherapy-induced hearing loss,” Bogyo’s team wrote in their report, published in the journal Science Translational Medicine.
“We chose ebselen as our lead compound because it has a clean safety profile in humans, and human pharmacokinetic data are available, thus giving it high potential for clinical translation.”
Tests in mice suggest it can stop C. diff from damaging the inside of the intestine. That might help prevent the constant diarrhea and the sepsis that kills most patients.
The drug’s a small molecule, meaning it could be taken as a pill.
Dr. Alexander Khoruts, a gastroenterologist at the University of Minnesota, says if the drug does work, it could save lives.
"Clostridium difficile is currently one of the top three superbugs identified by the CDC. C. difficile bacteria produce toxins, which damage the colon lining and cause inflammation called ‘C. difficile colitis’,” he said in a statement.
“The main protection against C. difficile is our own microbes present in the colon which get killed by routine antibiotics and are the main triggers of C. difficile infection. Not surprisingly, antibiotics which also constitute the only standard, FDA approved treatment for this infection often fail and the infection comes back within one to three weeks. Therefore, there is a critical need for non-antibiotic alternatives.”
One promising treatment is a fecal transplant. This transfers healthy colon bacteria from a volunteer into the patient.
Khoruts says the next step will be to test the ebselen pill in people.
“There are many unknown questions, including the dose of the new drug, its potential toxicity, and the duration of treatment that will be necessary,” he said.