A MAJOR international study has linked rifaximin with the global rise of a multidrug-resistant bacterial pathogen, vancomycin-resistant Enterococcus faecium (VREfm), a high-priority pathogen and leading cause of nosocomial infections.
The study, conducted by researchers from the University of Melbourne’s Doherty Institute and Austin Health, reveals that rifaximin, an antibiotic used prophylactically to prevent hepatic encephalopathy in patients with liver disease, may drive resistance to daptomycin, one of the last-resort antibiotics effective against VREfm infections.
Spanning 8 years, the authors utilised molecular microbiology, bioinformatics, and clinical science to analyse genetic changes in daptomycin-resistant VRE strains, changes absent in non-resistant variants. Results confirmed that rifaximin use induced amino acid changes within the bacterial RNA polymerase of VREfm, causing upregulation of a previously uncharacterised operon (prdRAB) that leads to cell membrane remodelling and cross-resistance to daptomycin through reduced binding of the antibiotic. Alarmingly, VREfm with these mutations were found to be spread globally, making this a major mechanism of resistance.
Until now, rifaximin had been considered ‘low risk’ for the development of antibiotic resistance. Glen Carter, Senior Research Fellow at the Doherty Institute, noted the significance of these results: “We’ve shown that rifaximin induces a type of daptomycin resistance that we haven’t observed before. This resistance could even spread to other hospital patients, an area we’re currently investigating.” Given these findings, clinicians may need to verify daptomycin’s efficacy before treating VRE in patients previously exposed to rifaximin.
The extensive use of rifaximin, especially among patients with liver cirrhosis, could be jeopardising the effectiveness of daptomycin, a crucial last-resort treatment for multidrug-resistant infections. These findings reveal how unexpected cross-resistance to antibiotics can disrupt global efforts aimed at preserving critical antibiotics.
These efforts reinforce the recent United Nations (UN) High-Level Meeting on antimicrobial resistance, where leaders pledged to reduce the 4.95 million annual deaths tied to antimicrobial resistance by 10% by 2030.
Reference
Turner AM et al. Rifaximin prophylaxis causes resistance to the last-resort antibiotic daptomycin. Nature. 2024; DOI:10.1038/s41586-024-08095-4.
