‘Almost untreatable’ superbug linked to common antibiotic

New research has highlighted the ‘critical need for a deeper understanding of the negative impacts of antibiotic use’ after an ‘almost untreatable’ superbug has been linked to a common antibiotic.

Newly published Australian-led research has revealed rifaximin, the antibiotic used for people with liver disease, is triggering resistance to another antibiotic, causing cross-resistance and an emergence of an ‘almost untreatable form’ of the antimicrobial resistant superbug, vancomycin-resistant enterococcus faecium (VRE).
 
Known to cause serious infections in hospitalised patients, VRE infections are treated as a last resort with daptomycin, for which the authors say resistance is ‘widely reported but unexplained’.
 
Now, they have discovered that the unrelated, previously considered ‘low-risk’ antibiotic rifaximin – used to prevent hepatic encephalopathy in patients with liver disease – can cause daptomycin-resistant VRE, raising concerns it could be transmitted to other patients in hospital.
 
Coming from the Doherty Institute, Melbourne University and Austin Health, the research team say the findings are a reminder of the need for better understanding of the negative impacts of antibiotic use, and reinforce the importance of antibiotic stewardship in clinical practice.
 
Co-author and infectious diseases physician, Associate Professor Jason Kwong, said the research has important clinical implications.
 
‘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,’ he 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.’
 
Conducted over eight years, the study used large-scale genomics to identify changes in the DNA of daptomycin-resistant VRE that were absent in susceptible strains, showing that rifaximin use caused such changes and resulted in the emergence of daptomycin-resistant VRE.
 
Rifaximin was found to trigger specific changes in the enzyme RNA polymerase within the bacteria, changing 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,’ lead author Dr Adrianna Turner said.
 
‘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.
 
‘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.’
 
Rifaximin has been considered ‘low risk’ for the development of antibiotic resistance, according to the authors, who debunk this theory and instead state 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’.
 
The research comes as the threat from antimicrobial resistance continues to rise globally with the World Health Organization warning it poses a significant threat. In 2019, and estimated 1.27 million deaths can be attributed.
 
In Australia, a recent report shows that antibiotic use in hospitals is ‘substantially higher’ than in comparable European countries and Canada. Meanwhile, Australia has one of the highest rates of resistance to VRE compared with almost all European countries.
 
Last month world leaders committed to ‘decisive action on antimicrobial resistance’ at the UN General Assembly High-Level Meeting on Antimicrobial Resistance. This includes reducing by 10% the estimated 4.95 million deaths associated with antimicrobial resistance per year, by 2030.
 
With findings from the Australian-led study demonstrating how ‘unanticipated’ antibiotic cross-resistance can undermine global strategies of antimicrobial stewardship, the authors conclude that their insights are ‘crucial for developing smarter, more sustainable strategies’ for life-saving antibiotics.
 
They highlight that patients with liver disease receiving rifaximin have been identified as a primary source for the emergence and spread of daptomycin-resistant VRE, and while effective for hepatic encephalopathy prophylaxis, rifaximin could be considered as a second-line option after other therapies for this indication.
 
‘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,’ Associate Professor Kwong said.
 
‘But we need to understand the implications going forward both when treating individual patients and from a public health perspective.’
 
Log in below to join the conversation.

antibiotic stewardship antibiotics antimicrobial resistance daptomycin hepatic encephalopathy liver disease rifaximin