University of Houston reports breakthrough antibiotic effective against C. difficile

Researchers at the University of Houston have reported that ibezapolstat, a novel antibiotic developed by Acurx Pharmaceuticals, has shown strong clinical trial results against Clostridioides difficile infection. The drug demonstrated high cure rates, no recurrence, and preservation of healthy gut bacteria, offering a potential alternative to vancomycin and fidaxomicin as resistance continues to rise.

The effectiveness of existing antibiotics to combat the superbug Clostridioides difficile (C. diff) has continued to decline but a research team at the University of Houston, Texas, has reported encouraging results from clinical trials of a novel treatment, ibezapolstat.

C. diff is a leading cause of death from gastroenteritis worldwide, with an estimated 453,000 infections and 29,300 deaths each year in the United States alone. The infection can cause diarrhoea and abdominal pain and progress to more serious conditions such toxic megacolon, sepsis and death. Current frontline treatments include vancomycin, which achieves a sustained clinical cure rate of between 42 and 71 per cent, and fidaxomicin at only two in three patients.

“Both vanco and fidaxo are associated with emerging antimicrobial resistance. C. diff infection recurrence is associated with increased mortality, decreased quality of life and higher healthcare costs. Novel antibiotics are urgently needed,” said Dr. Kevin Garey, Robert L. Boblitt Endowed Professor of Drug Discovery at the University of Houston College of Pharmacy and senior author of the paper.

Recurrent C. diff infections often occur when unbalance remains in the patient’s gut microbiota. Beneficial bacteria such as Bacillota, Bacteroidota and Actinomycetota are reduced, while harmful groups such as Pseudomonadota increase. This disruption weakens gut defences and prevents the breakdown of bile acids, allowing harmful bacteria to dominate.

“Ibezapolstat’s mechanism of action helps restore the healthy microbiota that causes C. diff recurrence,” said study lead author Dr. Taryn A. Eubank, research assistant professor of Pharmacy Practice and Translational Research at the University of Houston.

Unlike current therapies, ibezapolstat selectively kills C. diff while sparing protective bacteria in the gut.

“A randomised, double-blind, active-controlled study showed high rates of initial clinical cure in participants treated with ibezapolstat, with no recurrence,” said 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. diff infection,” he added.

Ibezapolstat is in development by Acurx Pharmaceuticals and is progressing towards phase III clinical trials. The phase II trial was conducted across 15 centres, mainly outpatient clinics and hospitals in the US, with enrolled participants aging between 18 and 90 with diarrhoea and a confirmed diagnosis of mild or moderate C. diff infection.

“This helps confirm the important anti-C diff recurrence properties of ibezapolstat,” added Eubank.

“The findings of our study support further clinical development of ibezapolstat into phase III clinical trials and eventual use in our patients,” said Garey.

For further reading please visit: 10.1016/j.lanmic.2025.101126