Penn State researchers have discovered that sevelamer, a medication commonly prescribed for kidney disease patients on dialysis, may offer a promising new weapon in the fight against antimicrobial resistance—a crisis the Centers for Disease Control and Prevention has labeled "one of the world's most urgent public health problems."
The research team, led by Amir Sheikhi, assistant professor of chemical engineering at Penn State, found that sevelamer effectively captures "off-target" antibiotics in the gut, potentially preventing bacteria from developing resistance to these critical medications.
How Antibiotics Drive Resistance
When patients receive intravenous antibiotics to treat infections, approximately 5-10% of these medications escape the bloodstream and end up in the gastrointestinal tract. These "off-target" antibiotics encounter large populations of bacteria in the gut, where they exert selective pressure but aren't present in sufficient concentrations to eliminate all bacteria.
"Antibiotics drive antibiotic-resistance," explained Andrew Read, senior vice president for research at Penn State and co-author of the study. "If you can inactivate antibiotics where they are not needed, you eliminate the driver of antibiotic resistance."
This problem is particularly concerning in healthcare settings, where patients often receive extended antibiotic treatments. The surviving bacteria evolve resistance mechanisms, creating increasingly dangerous pathogens that can cause serious infections throughout the body.
Sevelamer as an "Anti-Antibiotic"
The research, published in the journal Small, demonstrates that sevelamer can function as an "anti-antibiotic" by binding to vancomycin and daptomycin—two antibiotics commonly used against serious gram-positive bacterial infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA) and resistant enterococci.
In laboratory experiments, sevelamer captured low concentrations of daptomycin within minutes and vancomycin within hours. The drug successfully blocked antibiotic activity of daptomycin in vitro and vancomycin both in vitro and in live animal models.
"To the best of our knowledge, this is the first demonstration that an FDA-approved drug can effectively block vancomycin-driven resistance emergence in live organisms, presenting a novel and scalable strategy to combat antimicrobial resistance in health care settings," said Sheikhi.
Building on Previous Research
This work builds upon earlier studies by Read's team that showed cholestyramine—an FDA-approved drug for high cholesterol—could inactivate daptomycin. However, cholestyramine failed to remove vancomycin, leading researchers to investigate sevelamer as an alternative.
In the current study, researchers administered vancomycin or saline solution via injection to mice with Enterococcus faecium, a gut bacterium known to rapidly develop antibiotic resistance. Simultaneously, they fed the mice oral suspensions of sevelamer and later analyzed genetic material in the animals' fecal matter.
Clinical Implications
The findings have significant implications for human medicine. Since sevelamer is already FDA-approved for treating high phosphorus levels in dialysis patients, it has a well-established safety profile, making it a strong candidate for clinical application in combating antibiotic resistance.
"Developing anti-antibiotics, instead of new antibiotics, may be able to protect the effectiveness of current antibiotics," said Sheikhi, who is also affiliated with Penn State's Departments of Biomedical Engineering, Chemistry, and Neurosurgery.
This approach represents a paradigm shift in addressing antimicrobial resistance. Rather than focusing solely on developing stronger antibiotics—which bacteria eventually evolve to resist—researchers are exploring ways to preserve the effectiveness of existing medications.
Next Steps
The research team plans to conduct clinical trials to evaluate sevelamer's effectiveness in human patients receiving vancomycin or daptomycin. They also intend to explore whether sevelamer might prevent resistance evolution against other types of antibiotics excreted into the gastrointestinal tract.
The team is actively seeking collaborators with experience in clinical trials for antimicrobial resistance evaluation to advance this promising research.
This innovative approach could provide a valuable tool in the ongoing battle against antibiotic resistance, potentially extending the useful life of critical antibiotics and improving patient outcomes in healthcare settings worldwide.
