*Clostridioides difficile* — better known as C. diff — is one of the most feared infections in hospitals worldwide. It causes severe, sometimes fatal diarrhoea, primarily in older and immunocompromised patients. And its most frustrating characteristic? Even after successful treatment, it keeps coming back.
A new antibiotic developed at **Leiden University** in the Netherlands may finally change that. Called **EVG7**, it can eliminate C. diff at a remarkably low dose — and crucially, it does something no antibiotic has managed before: it leaves the beneficial gut bacteria that prevent relapse almost completely intact.
The findings were published in *Nature Communications*.
**The Problem with Current Treatments**
C. difficile infects around **500,000 Americans each year**, causing an estimated 15,000–30,000 deaths. The standard treatment is vancomycin — but there's a catch. Vancomycin kills C. diff, but it also destroys many of the other gut bacteria that normally act as a natural defence against the pathogen.
When those protective bacteria are gone, C. diff spores that survive in the gut can germinate and restart the infection. **One in five patients experiences a relapse within 30 days**. Some patients cycle through multiple rounds of infection and treatment, each time weakening their gut microbiome further.
It's a trap that existing antibiotics can't escape — because the very act of treating C. diff creates the conditions for it to return.
**EVG7: A Different Approach**
EVG7, developed in Professor Nathaniel Martin's research group at the **Institute of Biology Leiden (IBL)**, is a more potent and targeted derivative of vancomycin. The key insight wasn't just making it stronger — it was making it *smarter*.
Because EVG7 is many times more potent than vancomycin, researchers could administer a **much smaller dose**. And that smaller dose turned out to be the key. In mouse studies infected with C. diff:
- A low dose of EVG7 cleared the infection and **prevented it from returning** - A higher dose of EVG7 did *not* produce the same lasting protection - A comparable low dose of vancomycin had no lasting effect
The 'sweet spot' of EVG7 at low doses appeared to be the golden combination — effective enough to eliminate C. diff, gentle enough to preserve the microbiome.
**Why the Microbiome Matters**
When researchers examined the guts of treated mice, they found that those given low-dose EVG7 retained far more bacteria from the **Lachnospiraceae family** — a group of beneficial microbes that play a direct protective role against C. difficile reinfection.
These bacteria appear to physically outcompete C. diff spores, preventing them from germinating into new active bacteria. When they survive treatment, the infection doesn't come back.
'With existing antibiotics, C. difficile sometimes reappears just weeks after treatment,' said lead author Elma Mons. 'A low dose of EVG7 turned out to be the golden combination.'
**Less Likely to Cause Resistance**
There's another advantage: EVG7 appears **less prone to inducing antibiotic resistance** than existing treatments — a crucial feature as antibiotic resistance becomes a global health crisis.
The drug is still in preclinical development. Next steps include toxicity studies and human trials, which could begin within a few years if funding is secured. But the principle it proves — that precision antibiotics can distinguish between bacteria we want to kill and bacteria we need to protect — is one of the most exciting ideas in medicine right now.
For the hundreds of thousands of patients who experience the misery of C. diff infection every year — and the one-in-five who live through it twice — that would be transformative. 💊
*Sources: Leiden University Institute of Biology · Nature Communications, October 2025 · universiteitleiden.nl*
