As the effectiveness of antibiotics meant to fight the deadly superbug Clostridioides difficile, or C. diff, wanes, a research team at the 91 is seeing positive results of a new antibiotic on the scene — ibezapolstat — which is proving successful in fighting these infectious bacteria in clinical trials.
C. diff is the nation’s leading cause of death from gastroenteritis causing an estimated 453,000 infections yearly and 29,300 deaths. It causes gastrointestinal illness ranging from diarrhea and abdominal pain to toxic megacolon, sepsis and death.
Until now the frontline treatments for C. diff have been the antibiotics vancomycin, with a sustained clinical cure of 42% to 71%, and fidaxomicin at 67%.
And yet, a superbug would not be so deadly if it was not able to outlive the very medicines meant to destroy it.
“Both vanco and fidaxo are associated with emerging antimicrobial resistance. C. difficile infection recurrence is associated with increased mortality, decreased quality of life and higher healthcare costs. New antibiotics are urgently needed.” said Kevin Garey, Robert L. Boblitt Endowed Professor of Drug Discovery at the University of Houston College of Pharmacy and senior author on recent clinical trial results with ibezapolstat published in .
C. diff infections often return when the natural balance in the gut stays disrupted — good bacteria like Bacillota, Bacteroidota, and Actinomycetota are reduced, while harmful types like Pseudomonadota increase. These changes can weaken the gut’s defenses, causing a loss of the kind of bacteria that helps break down bile acids. When that happens, harmful bacteria can easily take over.
“Ibezapolstat’s mechanism of action helps restore the healthy microbiota that causes C. diff recurrence” said study lead author Taryn A. Eubank, research assistant professor of Pharmacy Practice and Translational Research at UH.


Enter ibezapolstat
Ibezapolstat has a way of working that kills harmful C. difficile bacteria without harming the good bacteria in the gut that protect against C. diff infections.
“A randomized, double-blind, active-controlled study showed high rates of initial clinical cure in participants treated with ibezapolstat, with no recurrence,” reports Garey.
“Ibezapolstat was found to be safe, well tolerated, and was associated with the preservation of key health-promoting bacteria responsible for bile acid homoeostasis, a key component in preventing recurrent C. difficile infection.”
Eubank added, “This helps confirm the important anti-C diff recurrence properties of Ibezapolstat.”
Ibezapolstat is being developed by Acurx Pharmaceuticals progressing towards phase III clinical trials. The study was conducted at 15 centers, primarily outpatient clinics and hospitals in the United States. Participants were aged 18–90 years, with diarrhea and a confirmed diagnosis of mild or moderate C. difficile infection.
“The findings of our study support further clinical development of ibezapolstat into phase III clinical trials and eventual use in our patients,” said Garey.