Symptoms of C. difficile span mild diarrhea to life-threatening colitis and death. Every year, around 500,000 patients are affected by the bacterium in the US, of which 30,000 cases are lethal. Antibiotics like oral vancomycin are among the standard of care treatments for C. difficile infections; however, they carry relapse rates of up to 25% within 2-8 weeks after treatment, with risk of recurrence increasing with each episode. Higher rates of resistance to current treatments underscore the need for new antibiotics.
EVG7 is a semisynthetic derivative of vancomycin that has previously outperformed vancomycin against drug-resistant gram-positive pathogens. In the current study, researchers investigated its effects on C. difficile. In vitro tests showed that C. difficile isolates are up to 16 times more sensitive to EVG7 than vancomycin.
The researchers also tested the drug in mouse models of C. difficile infection. Low-dose EVH7 was more effective at treating the infection and preventing recurrence than a 10-fold higher dose of vancomycin. Microbiome analyses and in vitro susceptibility testing also showed that EVG7 preserves Lachnospiraceae, a family of bacteria linked to protection against C. difficile colonization.
Toxicity studies are needed before the drug can move to human trials, said lead author Dr. Elma Mons of the Biological Chemistry Group at Leiden University in the Netherlands, in a press release.
"But that means finding investors. For antibiotics, that's not easy. Pharmaceutical companies make far less profit on them than on, say, cancer drugs, so interest is limited,” she added.
Mons and colleagues nevertheless believe that EVG7 could eventually become a leading treatment for C. difficile.
Sources: Science Daily, Nature Communications
