The antibiotic EVG7, developed in Leiden, has proven capable of fighting the dangerous gut bacterium C. difficile with only a minimal dose. What's more, the bacterium is far less likely to return, a major issue with existing antibiotics. The research was published in Nature Communications.
C. difficile is a persistent intestinal bacterium that can cause severe illness, particularly in older people and those with weakened health. The bacterium produces a toxin that leads to severe diarrhea. Current treatments are not always effective, as the infection often returns.
The new antibiotic EVG7, recently developed in Professor Nathaniel Martin's research group at the Institute of Biology Leiden (IBL), could change that. EVG7 is a stronger and more efficient version of the commonly used antibiotic vancomycin.
'With existing antibiotics, C. difficile sometimes reappears just weeks after treatment,' says researcher and lead author Elma Mons. This happens partly because the bacterium leaves behind spores, which can develop into new bacteria. Causing the infection to return.
Much lower dose, yet more effective
Mons and her team investigated the effect of EVG7 on C. difficile. Because the antibiotic is many times more potent than vancomycin, they administered a much smaller dose in a study on mice. The results were striking: the C. difficile bacteria were far less likely to return. A lower dose of vancomycin did not have the same effect, nor did a higher dose of EVG7. A low dose of EVG7 turned out to be the golden combination.
To understand why, the researchers examined the microbiome of the treated mice: the collection of bacteria living in their intestines. They found that mice given a low dose of EVG7 retained far more beneficial bacteria (from the Lachnospiraceae family). 'Those bacteria actually protect against C. difficile,' says Mons.
In other words: while existing treatments tend to kill many bacteria essential for good health, a low dose of EVG7 leaves most of them intact. These beneficial bacteria help prevent the infection from recurring by keeping residual spores from growing into harmful C. difficile bacteria. 'That approach fits a growing trend among doctors to preserve the microbiome as much as possible,' Mons explains
Lower risk of resistance
In theory, using lower antibiotic doses can promote resistance. 'That happens when you don't completely kill the bacteria but merely irritate them,' Mons says. 'They can then come back stronger.' That's not the case with EVG7: even a low dose is strong enough to kill C. difficile effectively. Moreover, EVG7 appears less prone to inducing resistance.
Mons hopes that sufficient funding will become available for the next stages of development. After the required toxicity studies, the drug could be tested in humans 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.'
Still, the researchers hope that EVG7 will eventually top the list of treatments for C. difficile. '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 on the 10th of October 2025 in Nature Communications. The research was carried out in collaboration with the groups of Wiep Klaas Smits (Leiden University Medical Center) and Casey Theriot (North Carolina State University).
