New "super antibiotic" stops deadly gut infection without destroying the microbiome

C. difficile is a stubborn intestinal bacterium that can cause serious illness, especially in older adults and people with weakened health. It releases toxins that trigger severe diarrhea and inflammation in the gut. Although antibiotics are commonly used to treat the infection, many patients experience relapses after treatment.

The experimental antibiotic EVG7 was created in the research group of Professor Nathaniel Martin at the Institute of Biology Leiden (IBL). The drug is designed as a more powerful and efficient version of the widely used antibiotic vancomycin.

"With existing antibiotics, C. difficile sometimes reappears just weeks after treatment," says researcher and lead author Elma Mons. This is partly because the bacterium forms spores that can survive treatment and later grow into new bacteria. Causing the infection to return.

Low Dose Antibiotic Shows Strong Results

Mons and her colleagues studied how EVG7 affects C. difficile infections in mice. Because the drug is far more potent than vancomycin, the researchers tested it at a much smaller dose. The results were notable. The infection was much less likely to come back in mice treated with a low dose of EVG7.

Other combinations did not work as well. A reduced dose of vancomycin failed to prevent relapse, and a higher dose of EVG7 also produced weaker results. The researchers found that a low dose of EVG7 delivered the best outcome.

Protecting the Gut Microbiome

To understand why the lower dose worked so well, the team analyzed the microbiome of the treated mice. The microbiome refers to the community of bacteria that naturally live in the intestines. Mice treated with a small dose of EVG7 kept far more beneficial bacteria, especially members of the Lachnospiraceae family.

"Those bacteria actually protect against C. difficile," says Mons.

In contrast, many existing antibiotics wipe out large portions of the microbiome, including helpful microbes that support gut health. EVG7 appears to leave most of these protective bacteria intact. These microbes help stop leftover spores from growing into harmful C. difficile bacteria and triggering another infection. 'That approach fits a growing trend among doctors to preserve the microbiome as much as possible,' Mons explains

Lower Risk of Antibiotic Resistance

Using smaller antibiotic doses can sometimes raise concerns about antibiotic resistance. "That happens when you don't completely kill the bacteria but merely irritate them," Mons says. "They can then come back stronger."

According to the researchers, EVG7 does not appear to have that problem. Even at a low dose, the drug is powerful enough to effectively eliminate C. difficile. Early findings also suggest that the antibiotic is less likely to drive resistance.

Next Steps Toward Human Trials

Mons hopes funding will become available so the research can move forward. Before the drug can be tested in people, scientists must first complete toxicity studies. If those studies are successful, clinical trials could begin within a few years.

"But that means finding investors," she adds. "For antibiotics, that's not easy. Pharmaceutical companies make far less profit on them than on, say, cancer drugs, so interest is limited."

Despite these challenges, researchers believe EVG7 could eventually become a leading treatment for C. difficile infections. "If a patient relapses and needs another hospital admission, that's costly too," Mons points out.

The paper 'Experimental glycopeptide antibiotic EVG7 prevents recurrent Clostridioides difficile infection by sparing members of the Lachnospiraceae family' was published in Nature Communications. The research involved collaboration with the groups of Wiep Klaas Smits (Leiden University Medical Center) and Casey Theriot (North Carolina State University).