To address the growing antimicrobial resistance problem, scientists have been searching nature in attempts to find new classes of antibiotics, optimizing existing ones, or designing new antimicrobial molecules. These efforts all focus on one thing: finding stronger, newer antibiotics.
Unnecessary exposure to antibiotics enables bacteria to evolve defenses and increases resistance risks. While caution in prescribing antibiotics is an important part of limiting unnecessary antibiotic exposure, another strategy hinges on limiting where antibiotics can exist in the body. This means, making sure antibiotics don’t make their way to other places in the body beyond the infection sites.
An example of “off target” antibiotics is when antibiotics are used to treat bloodstream infections. Two antibiotics – vancomycin and daptomycin – are used to treat multidrug-resistant Enterococcus infections when all other antibiotics have failed. These antibiotics are given intravenously and any excess is eliminated in urine. However, up to 10% of the antibiotic enters the gastrointestinal tract where it can drive gut microbes to evolve resistance against the antibiotic.
A recent study found that the FDA-approved dialysis drug, sevelamer, could inactivate vancomycin and daptomycin in the gut. The drug inactivates vancomycin within hours and daptomycin within minutes. They studied this effect in mice colonized with intestinal bacteria by treating mice with vancomycin for five days, collecting fecal samples throughout this period, and quantifying the levels of vanA gene in the fecal samples. The vanA gene gives bacteria vancomycin resistance so presumably, higher levels of this gene means more resistance to vancomycin. While on vancomycin, some mice got sevelamer, while others did not. They found that sevelamer prevented the development of vancomycin resistance in the mice. In fact, a twice-a-day treatment of sevelamer reduced vanA levels by 75%.
A previous study from the research group found that the cholesterol drug, cholestyramine, inactivated daptomycin, but not vancomycin.
Sevelamer and cholestyramine already have the FDA’s stamp of approval for different applications, so they could be strong candidates for future clinical trials to test their effectiveness in humans receiving these antibiotics for bloodstream infections.
While the results of the study are interesting on its own, I’m curious about how such a concept could be applied to other antibiotics and in other settings. For infections like ear infections or sinus infections, doctors prescribe oral antibiotics that first need to make their way into the intestines before they travel through the bloodstream, are metabolized, and finally, reach the sites of infection. This seems like it’s more difficult to ensure antibiotics only reach their intended sites. Other antibiotics, like topicals, also get absorbed in the bloodstream, even if they are only needed on the skin – could there be a way to prevent it from making it into the bloodstream?
I’m very curious what’s next for this type of research. As antibiotic resistance becomes more and more of a problem, we must explore new strategies beyond reducing antibiotic overprescribing to prevent the spread of resistance genes.
Further reading:
Polymeric Anti-Antibiotic Microparticles to Prevent Antibiotic Resistance Evolution. Small. 2025.
Featured image by Fayette Reynolds.
