Turner, Adrianna M. and Li, Lucy and Monk, Ian R. and Lee, Jean Y. H. and Ingle, Danielle J. and Portelli, Stephanie and Sherry, Norelle L. and Isles, Nicole and Seemann, Torsten and Sharkey, Liam K. and Walsh, Calum J. and Reid, Gavin E. and Nie, Shuai and Eijkelkamp, Bart A. and Holmes, Natasha E. and Collis, Brennan and Vogrin, Sara and Hiergeist, Andreas and Weber, Daniela and Gessner, Andre and Holler, Ernst and Ascher, David B. and Duchene, Sebastian and Scott, Nichollas E. and Stinear, Timothy P. and Kwong, Jason C. and Gorrie, Claire L. and Howden, Benjamin P. and Carter, Glen P. (2024) Rifaximin prophylaxis causes resistance to the last-resort antibiotic daptomycin. NATURE, 635 (8040). ISSN 0028-0836, 1476-4687
Full text not available from this repository. (Request a copy)Abstract
Multidrug-resistant bacterial pathogens like vancomycin-resistant Enterococcus faecium (VREfm) are a critical threat to human health1. Daptomycin is a last-resort antibiotic for VREfm infections with a novel mode of action2, but for which resistance has been widely reported but is unexplained. Here we show that rifaximin, an unrelated antibiotic used prophylactically to prevent hepatic encephalopathy in patients with liver disease3, causes cross-resistance to daptomycin in VREfm. Amino acid changes arising within the bacterial RNA polymerase in response to rifaximin exposure cause upregulation of a previously uncharacterized operon (prdRAB) that leads to cell membrane remodelling and cross-resistance to daptomycin through reduced binding of the antibiotic. VREfm with these mutations are spread globally, making this a major mechanism of resistance. Rifaximin has been considered 'low risk' for the development of antibiotic resistance. Our study shows that this assumption is flawed and that widespread rifaximin use, particularly in patients with liver cirrhosis, may be compromising the clinical use of daptomycin, a major last-resort intervention for multidrug-resistant pathogens. These findings demonstrate how unanticipated antibiotic cross-resistance can undermine global strategies designed to preserve the clinical use of critical antibiotics. Rifaximin use, particularly in patients with liver cirrhosis, may be compromising the clinical use of daptomycin.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SEQUENCE TYPING SCHEME; ENTEROCOCCUS-FAECIUM; MECHANISMS; ALIGNMENT; EMERGENCE; ALGORITHM; PACKAGE; TREE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Aug 2025 07:14 |
| Last Modified: | 20 Aug 2025 07:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65599 |
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