New research has found that ibuprofen and paracetamol may be contributing to antimicrobial resistance – particularly when used in combination.
Researchers from the University of South Australia conducted a study in residential aged care facilities (RACFs) on antimicrobial resistance, looking at the interactions between organisms such as Escherichia coli, non-antibiotic medicines and the broad-spectrum antibiotic ciprofloxacin, Lead Researcher Associate Professor Rietie Venter told Australian Pharmacist.
‘We also looked at an antibiotic-sensitive microorganism we isolated from a resident and we treated this microorganism with nine medications which are frequently used in the older population,’ she said.
The microorganisms were treated with the medicines – including ibuprofen, diclofenac, paracetamol, furosemide, metformin, atorvastatin, tramadol, temazepam and pseudoephedrine – both individually and in combinations of two.
Paracetamol and ibuprofen were found to increase ciprofloxacin resistance in this gut bacterium separately, and even more so when combined.
‘When bacteria were exposed to ciprofloxacin alongside ibuprofen and paracetamol, they developed more genetic mutations than with the antibiotic alone, helping them grow faster and become highly resistant,’ A/Prof Venter said.
‘Worryingly, the bacteria were not only resistant to the antibiotic ciprofloxacin, but increased resistance was also observed to multiple other antibiotics from different classes.’
How do paracetamol and ibuprofen increase antimicrobial resistance?
Sequencing in follow-up studies revealed how the organism acquired mutations, A/Prof Venter said.
‘Evolution is turbocharged in these little microbes; under ideal conditions, organisms like the one we used double every 20 minutes,’ she said.
‘If they get stressed by the addition of paracetamol and an antibiotic, they mutate. While some of those mutations make them more vulnerable, many might actually make them resistant.’
Mutations conferring resistance to ciprofloxacin were identified, along with efflux pumps – membrane proteins that expel antibiotics before they can reach their targets.
‘When used in combination, a synergy between the two medicines causes increased mutations, leading to higher levels of resistance.’
On a positive note, none of the other nine medicines analysed in the research increased antimicrobial resistance in the gut bacteria.
‘None of the other medications, when combined with ibuprofen, were worse than ibuprofen by itself,’ she said.
Are there certain populations who could be more at risk?
Older Australians, particularly those in RACFs, are a reservoir for antimicrobial resistance.
‘Older people are more likely to be prescribed multiple medications – not just antibiotics, but also medicines for pain, sleep, or blood pressure – making them an ideal breeding ground for gut bacteria to become resistant to antibiotics,’ A/Prof Venter.
While more research is needed before any policy change may be considered, A/Prof Venter thinks it’s important to understand why these analgesics are being taken together and to consider alternative options.
‘We would love to do more research to see if there is a way we can exchange an [analgesic] for another pain medication that doesn’t cause the enhanced antimicrobial resistance, or if there’s a certain time between taking them that’s better.’
What advice should pharmacists provide to patients?
It’s common for antibiotics to be combined with over-the-counter analgesics. For example, a woman with a urinary tract infection who is taking an antibiotic might also take an analgesic for pain relief, or a child with a bacterial infection such as tonsillitis who is prescribed azithromycin could be administered ibuprofen and paracetamol to manage a high fever.
The research provides an opportunity for pharmacists to raise awareness among patients about the risks of antimicrobial resistance, A/Prof Venter said.
‘It’s well known that the use of antibiotics may cause antimicrobial resistance,’ she said. ‘But it’s not considered that these frequently used medications can also increase antimicrobial resistance.’
The paracetamol scheduling changes introduced earlier this year are also an important step in building public awareness that these medicines are not as harmless as they might appear, A/Prof Venter believes.
‘Compared to many other medications, people tend to think of [paracetamol and ibuprofen] as completely harmless,’ she said. ‘So strategies such as smaller pack sizes can lead to changes in behaviour.’
PSA’s Medicine safety: Child and adolescent care report found that pharmacists have an increasing role in helping patients use common analgesics safely, with approximately 16% of pharmaceutical poisoning hospital admissions in children under 5 years of age being attributed to paracetamol.
‘By limiting the maximum pack sizes of paracetamol, we are opening the door to have a conversation about the risks and benefits of these medicines – both in the pharmacy and at home – and take steps as a community to promote the safe use of medicines,’ said PSA National President Associate Professor Fei Sim FPS.
‘By involving pharmacists in the supply of paracetamol in larger pack sizes, we strike the right balance between access and safety, giving pharmacists the opportunity to help patients manage their pain effectively while reducing the risk of misuse and harm.’
