Antibiotic resistance is one of the greatest challenges in modern medicine. Antibiotic resistance is indeed a major cause of mortality worldwide, causing more deaths than AIDS and malaria. This risk is increasing rapidly and is expected to cause the death of nearly 40 million people by 2050. Fighting antibiotic resistance is undoubtedly urgent and is becoming a scientific priority, with the development of new antibiotics which could replace the old ones, which are now ineffective.
But this fight also requires reducing the risks of antibiotic resistance, and one of these risks is polypharmacy, that is, taking several medications simultaneously. According to a new study from the University of South Australia, even seemingly harmless drugs can promote antibiotic resistance in bacteria if they are administered at the same time. The study was published on August 25, 2025, in the journal npj Antimicrobials and Resistance.
Some drugs help bacteria protect themselves from antibiotics
The researchers studied the effect of nine drugs (including paracetamol, ibuprofen, tramadol, and metformin) on antibiotic resistance, whether or not they were used in conjunction with the antibiotic ciprofloxacin, which is commonly used for urinary tract infections, among other conditions. Two different strains of the bacteria E. coli were treated with these drug combinations, showing that some of these mixtures help the bacteria defend themselves against the antibiotic. And this is even when these drugs are administered has concentrations similar to those found in the intestines of a person who has taken them.
In isolation, none of these drugs had any effect on these bacteria. Only in the presence of ciprofloxacin did any effect appear. Thus, paracetamol and ibuprofen increased the growth rate of the bacteria. despite the action of the antibiotic, compared to what was observed with the latter alone.
Paracetamol and ibuprofen promote bacterial mutagenesis in the presence of an antibiotic
This protection is thought to be partly due to a higher mutation rate in the presence of these drugs and the antibiotic. After culturing the bacteria with one of these drugs and the antibiotic for 48 hours, the researchers identified a large number of mutants that were partially resistant to the antibiotic. For these, the antibiotic dose had to be increased up to 16 times to kill them. Worse, this resistance created in the presence of ciprofloxacin was valid not only against this antibiotic, but also against others, such as levofloxacin andecefepim.
And this antibiotic resistance effect was even higher when several drugs were present at the same time (for example, paracetamol simultaneously with ibuprofen and the antibiotic). According to the authors, this underlines the risk of antibiotic resistance in polypharmacy, when a person receives several treatments at the same time.This is very common in nursing homes, as they are often treated with different medications at the same time, including antibiotics, painkillers, sleep aids, and more., recalls the study's director, Henrietta Venter, in a press release. This is an ideal context for the emergence of antibiotic-resistant bacteria.”
These mutations promote antibiotic resistance
The researchers sequenced the genomes of these resistant mutants to identify the genes altered by these mutations. Several of these involved proteins related to the stress response, as well as efflux pumps, which bacteria use to expel toxic compounds. These mutations increased the expression of these pumps, which would allow the bacteria to get rid of the antibiotic. This hypothesis was confirmed by treating the bacteria with a blocker of these efflux pumps: without them, the bacteria's antibiotic resistance disappeared or decreased significantly.
“This study reminds us that it is important to consider the risks of using several medications at the same time., underlines Henrietta Venter. This does not mean that we should stop these treatments, only that we should be careful about how they might interact with antibiotics.”
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