A recent study reveals that an antibiotic used for liver disease patients may increase their risk of contracting a dangerous superbug.
An international team of researchers has discovered that rifaximin, a commonly prescribed antibiotic for liver disease patients, is contributing to the global rise of a highly resistant strain of vancomycin-resistant Enterococcus faecium (VRE). This superbug, which frequently causes severe infections in hospitalized patients, is becoming increasingly difficult to treat.
The study, published in Nature, reveals that rifaximin use is accelerating resistance to daptomycin—one of the last remaining effective antibiotics against VRE infections.
Led by scientists from the University of Melbourne’s Peter Doherty Institute for Infection and Immunity (Doherty Institute) and Austin Health, the research underscores the urgent need for a more comprehensive understanding of the unintended consequences of antibiotic use. It highlights the critical importance of responsible antibiotic prescribing to mitigate the spread of antimicrobial resistance.
Their findings reinforce the recent political declaration of the UN General Assembly High-Level Meeting on Antimicrobial Resistance (26 Sept 2024), where world leaders committed to decisive action on antimicrobial resistance, including reducing the estimated 4.95 million AMR-associated human deaths annually by 10 per cent by 2030.
How Rifaximin Promotes Antibiotic Resistance
The eight-year study drew on several disciplines, including molecular microbiology, bioinformatics and clinical science. Using large-scale genomics – the study of an organism’s DNA makeup – the scientists were able to identify changes in the DNA of daptomycin-resistant VRE that were absent in susceptible strains. Subsequent laboratory experimentation and clinical studies showed that rifaximin use caused these changes and resulted in the emergence of daptomycin-resistant VRE.
The University of Melbourne’s Dr Glen Carter, a Senior Research Fellow at the Doherty Institute and senior author of the study, said the research challenges the long-held belief that rifaximin poses a ‘low risk’ for causing antibiotic resistance.
“We’ve shown that rifaximin makes VRE resistant to daptomycin in a way that has not been seen before,” Dr Carter said.
“It is also of concern that these daptomycin-resistant VRE might be transmitted to other patients in the hospital; a hypothesis that we are presently investigating.”
A “Supercharged” Resistance Mechanism
The University of Melbourne’s Dr Adrianna Turner, a Research Officer at the Doherty Institute and first author of the study, said rifaximin triggers specific changes in an enzyme called RNA Polymerase within the bacteria. These changes “upregulate” a previously unknown gene cluster (prdRAB) leading to alterations in the VRE cell membrane and causing cross-resistance to daptomycin.
“When bacteria become resistant to an antibiotic, it’s a bit like gaining a new ability in a video game, like super-speed. But when exposed to rifaximin, the VRE bacteria don’t just get one boost – they gain multiple abilities, like super-speed and super-strength, allowing them to easily defeat even the final boss, which in this case is the antibiotic daptomycin,” Dr Turner said.
“In other words, rifaximin doesn’t just make bacteria resistant to one antibiotic; it can make them resistant to others, including critical last-resort antibiotics like daptomycin.”
Associate Professor Jason Kwong, Infectious Diseases Physician at Austin Health and lead investigator of the clinical studies, emphasized two critical implications of the findings.
“Firstly, clinicians must exercise caution when treating VRE infections in patients who have been taking rifaximin, since daptomycin’s efficacy may be compromised, necessitating laboratory verification before use,” Associate Professor Kwong said.
“Secondly, the findings underscore the importance of regulatory bodies considering ‘off-target and cross class’ effects when approving new drugs. For antibiotics, this means understanding whether exposure to one agent, like rifaximin, could induce resistance against other antibiotics – even those that work differently.
“Rifaximin is still a very effective medication when used appropriately and patients with advanced liver disease who are currently taking it should continue to do so. But we need to understand the implications going forward both when treating individual patients and from a public health perspective.”
The University of Melbourne’s Dr Claire Gorrie, a senior bioinformatician from the Doherty Institute and co-senior author, said the research highlights how cutting-edge technologies, combined with interdisciplinary collaboration, can uncover exactly how and why bacteria develop resistance to antibiotics – even those they’ve never encountered.
“These insights are crucial for developing smarter, more sustainable strategies for antibiotic use, especially as these life-saving drugs become an increasingly precious resource,” Dr Gorrie said.
Professor Benjamin Howden, the Director of the Microbiological Diagnostic Unit Public Health Laboratory at the Doherty Institute and an Infectious Diseases Physician at Austin Health, whose laboratory led the project, said the research will help ensure daptomycin remains an effective antibiotic for treating severe VRE infections in hospitals in Australia and around the world, particularly in the most vulnerable patients.
“Our findings highlight the critical need for effective genomics-based surveillance to detect emerging antimicrobial resistance. They also underscore the importance of judicious antibiotic use to safeguard vital last-resort treatments like daptomycin,” Professor Howden concluded.
Reference: “Rifaximin prophylaxis causes resistance to the last-resort antibiotic daptomycin” by Adrianna M. Turner, Lucy Li, Ian R. Monk, Jean Y. H. Lee, Danielle J. Ingle, Stephanie Portelli, Norelle L. Sherry, Nicole Isles, Torsten Seemann, Liam K. Sharkey, Calum J. Walsh, Gavin E. Reid, Shuai Nie, Bart A. Eijkelkamp, Natasha E. Holmes, Brennan Collis, Sara Vogrin, Andreas Hiergeist, Daniela Weber, Andre Gessner, Ernst Holler, David B. Ascher, Sebastian Duchene, Nichollas E. Scott, Timothy P. Stinear, Jason C. Kwong, Claire L. Gorrie, Benjamin P. Howden and Glen P. Carter, 23 October 2024, Nature.
DOI: 10.1038/s41586-024-08095-4
The team’s main collaborators were Bio21 Molecular Science and Biotechnology Institute; University Medical Center, Regensburg, Germany; The University of Queensland; and Flinders University, Adelaide.
The study was funded by the National Health and Medical Research Council.

News
Repurposed drugs could calm the immune system’s response to nanomedicine
An international study led by researchers at the University of Colorado Anschutz Medical Campus has identified a promising strategy to enhance the safety of nanomedicines, advanced therapies often used in cancer and vaccine treatments, [...]
Nano-Enhanced Hydrogel Strategies for Cartilage Repair
A recent article in Engineering describes the development of a protein-based nanocomposite hydrogel designed to deliver two therapeutic agents—dexamethasone (Dex) and kartogenin (KGN)—to support cartilage repair. The hydrogel is engineered to modulate immune responses and promote [...]
New Cancer Drug Blocks Tumors Without Debilitating Side Effects
A new drug targets RAS-PI3Kα pathways without harmful side effects. It was developed using high-performance computing and AI. A new cancer drug candidate, developed through a collaboration between Lawrence Livermore National Laboratory (LLNL), BridgeBio Oncology [...]
Scientists Are Pretty Close to Replicating the First Thing That Ever Lived
For 400 million years, a leading hypothesis claims, Earth was an “RNA World,” meaning that life must’ve first replicated from RNA before the arrival of proteins and DNA. Unfortunately, scientists have failed to find [...]
Why ‘Peniaphobia’ Is Exploding Among Young People (And Why We Should Be Concerned)
An insidious illness is taking hold among a growing proportion of young people. Little known to the general public, peniaphobia—the fear of becoming poor—is gaining ground among teens and young adults. Discover the causes [...]
Team finds flawed data in recent study relevant to coronavirus antiviral development
The COVID pandemic illustrated how urgently we need antiviral medications capable of treating coronavirus infections. To aid this effort, researchers quickly homed in on part of SARS-CoV-2's molecular structure known as the NiRAN domain—an [...]
Drug-Coated Neural Implants Reduce Immune Rejection
Summary: A new study shows that coating neural prosthetic implants with the anti-inflammatory drug dexamethasone helps reduce the body’s immune response and scar tissue formation. This strategy enhances the long-term performance and stability of electrodes [...]
Scientists discover cancer-fighting bacteria that ‘soak up’ forever chemicals in the body
A family of healthy bacteria may help 'soak up' toxic forever chemicals in the body, warding off their cancerous effects. Forever chemicals, also known as PFAS (per- and polyfluoroalkyl substances), are toxic chemicals that [...]
Johns Hopkins Researchers Uncover a New Way To Kill Cancer Cells
A new study reveals that blocking ribosomal RNA production rewires cancer cell behavior and could help treat genetically unstable tumors. Researchers at the Johns Hopkins Kimmel Cancer Center and the Department of Radiation Oncology and Molecular [...]
AI matches doctors in mapping lung tumors for radiation therapy
In radiation therapy, precision can save lives. Oncologists must carefully map the size and location of a tumor before delivering high-dose radiation to destroy cancer cells while sparing healthy tissue. But this process, called [...]
Scientists Finally “See” Key Protein That Controls Inflammation
Researchers used advanced microscopy to uncover important protein structures. For the first time, two important protein structures in the human body are being visualized, thanks in part to cutting-edge technology at the University of [...]
AI tool detects 9 types of dementia from a single brain scan
Mayo Clinic researchers have developed a new artificial intelligence (AI) tool that helps clinicians identify brain activity patterns linked to nine types of dementia, including Alzheimer's disease, using a single, widely available scan—a transformative [...]
Is plastic packaging putting more than just food on your plate?
New research reveals that common food packaging and utensils can shed microscopic plastics into our food, prompting urgent calls for stricter testing and updated regulations to protect public health. Beyond microplastics: The analysis intentionally [...]
Aging Spreads Through the Bloodstream
Summary: New research reveals that aging isn’t just a local cellular process—it can spread throughout the body via the bloodstream. A redox-sensitive protein called ReHMGB1, secreted by senescent cells, was found to trigger aging features [...]
AI and nanomedicine find rare biomarkers for prostrate cancer and atherosclerosis
Imagine a stadium packed with 75,000 fans, all wearing green and white jerseys—except one person in a solid green shirt. Finding that person would be tough. That's how hard it is for scientists to [...]
Are Pesticides Breeding the Next Pandemic? Experts Warn of Fungal Superbugs
Fungicides used in agriculture have been linked to an increase in resistance to antifungal drugs in both humans and animals. Fungal infections are on the rise, and two UC Davis infectious disease experts, Dr. George Thompson [...]