The rise of an almost untreatable superbug has been linked to a common antibiotic, an Australian-led study has found.
The study – published in Nature – found that rifaximin, an antibiotic used to treat liver disease, causes resistance to another antibiotic, daptomycin.
Daptomycin is one of the few drugs that is effective against vancomycin-resistant enterococcus (VRE), a contagious bacterial infection that can cause serious reactions in hospitalised patients.
Dr Adrianna Turner, the study’s lead author, said the “really surprising” finding was the first recorded instance of an antibiotic causing resistance to one in a different class. It was previously thought that the risk of antibiotic resistance only applied to the one antibiotic.
The findings also overturned the widely held idea that rifaximin was a low-risk antibiotic.
Last month international leaders committed to decisive action on antimicrobial resistance – the development of bacteria to resist treatment. This included the aim of reducing the estimated global 4.95m deaths associated with antimicrobial resistance annually by 10 percentage points by 2030.
Turner said when bacteria became resistant to an antibiotic, “it’s a bit like gaining a new ability in a video game”.
“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.”
Rifaximin use triggers changes in an enzyme within the bacteria, which then leads to changes in the VRE’s cell membrane, causing cross-resistance, researchers from the Doherty Institute and Austin Health found.
Turner did not rule out the possibility that other antibiotics could create resistance to antibiotics in different classes.
Researchers are now investigating whether daptomycin-resistant strains of VRE may be transmitted to other patients within the hospital.
The eight-year study involved genomic analyses of isolates from patients from Australia and Germany, and used animal models to support the hypotheses.
Turner said the findings highlighted the need for surveillance and investigation into how bacteria become antibiotic-resistant, allowing researchers to create diagnostic tests and genomic surveillance to understand the prevalence of such bacteria.
Prof Jason Kwong, from Austin Health, emphasised that rifaximin is still effective when used appropriately and those taking it to treat advanced liver disease 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,” he said.
He advised clinicians treating patients with VRE who have taken rifaximin to confirm that daptomycin is working via a lab test, as its efficacy may be affected.
Kwong emphasised the importance of drug regulators considering whether the use of one drug makes another less effective when approving new drugs.
Prof Martina Sanderson-Smith, a molecular bacteriologist at the University of Wollongong, said the finding that antibiotic resistance can affect different types of antibiotics was “really concerning and interesting”.
She said the findings highlighted the difficulties in the responsible use and prescription of antibiotics, and the need to balance safety with clinical need.
“We need to better understand the possible sort of consequences of prescribing all classes of antibiotics on this idea of shared resistance across antibiotic classes, so that clinicians can make more informed decisions,” she said.
