You probably keep one in your handbag and another in your office drawer, just in case. When a headache hits or the first signs of a fever creep in, ibuprofen and other painkillers are the pills we reach for without thinking twice. And while these are best known for quick relief, emerging research is starting to uncover effects that go beyond pain control.

“Common over-the-counter painkillers like ibuprofen and acetaminophen can increase antibiotic resistance by increasing genetic mutation rates in bacteria such as E. coli,” says 

Dr Brian Honeyman, M.D., Ph.D., Clinical Advisor at iRely Recovery. 

With more than 73 million NSAID prescriptions written each year, and an estimated 30 million people using them daily, these familiar, easily accessible pills may be quietly contributing to a much bigger global health problem. 

But how can routine, over-the-counter painkillers nudge bacteria to become tougher, smarter, and harder to kill?

Antibiotic Resistance and Its Threat to Global Health

Antibiotic resistance occurs when bacteria in the body adapt to survive against medicine designed to kill them or stop their growth. As Dr Honeyman explains: “Antibiotic resistance occurs when bacteria evolve to defeat the drugs designed to kill them, turning treatable infections into major public health threats.”

It is one form of antimicrobial resistance, a broader problem that can also affect viruses, fungi, and parasites. Instead of being eliminated, these microbes evolve and become smarter, learning survival tricks that help them persist and spread so they are harder to defeat, creating a problem that is growing in scale. 

In a 2025 report, the World Health Organization (WHO) shared that one in six laboratory-confirmed bacterial infections causing common infections in people worldwide in 2023 were resistant to antibiotic treatments. 

This trend poses a major threat to the many gains of modern medicine. A person living with antibiotic resistance may find that common infections that are straightforward to treat, such as UTIs or minor wound infections, can become life-threatening when antibiotics stop working. The ripple effects stretch to routine medical care, where antibiotics are a safety net protecting people during surgeries, chemotherapy, or even childbirth. As resistance rises, this safety weakens, leaving doctors with fewer effective options. 

Some of the most worrying cases involve bacteria like E. coli and K. pneumoniae, both known to cause severe bacterial infections often resulting in sepsis, organ failure, and death. Today, more than 40% of E. coli and over 55% of K. pneumoniae globally are resistant to treatment.

The scale of this problem could very well worsen, with the potential to become one of the most serious threats to global health. By 2050, the United Nations projects that antibiotic-resistant bacterial infections could rival or exceed cancer as a leading cause of death. 

Painkillers and the Bacterial Stress Response

Discussions around antibiotic resistance have traditionally focused on antibiotic misuse: using these drugs when they aren’t needed, taking the wrong dose, or stopping treatment too early. But new findings from the University of South Australia paint a more complex picture, indicating that everyday painkillers like ibuprofen and acetaminophen can also influence how bacteria behave.

In laboratory experiments, each of these non-antibiotic medications (NAMs) was shown to contribute to antibiotic resistance on its own, with even stronger effects when certain painkillers such as ibuprofen and paracetamol were used together.

This impact appeared to grow stronger when painkillers were combined with antibiotics. As Dr Brian Honeyman explains, “when these non-antibiotic medications are taken with antibiotics like ciprofloxacin, they can trigger bacterial defense mechanisms.”

Unlike antibiotics, which drive resistance by killing off more vulnerable bacteria and giving naturally resistant strains room to multiply over time following misuse, painkillers don’t directly target bacteria. Instead, some painkillers appear to create a mild stress environment for bacteria.

To cope, bacteria may switch on protective systems that help them ride out threats, and, in some cases, become less sensitive to antibiotics. This stress can also increase the likelihood of genetic changes, allowing some bacteria to mutate in ways that help them withstand antibiotic treatment.

At the cellular level, painkillers have been shown to activate efflux pumps: tiny proteins bacteria use to flush out unwanted substances, which, unfortunately, includes antibiotics. 

Real-World Implications

To explore the connection between painkillers and antibiotic resistance, researchers at the University of South Australia examined the gut bacteria of older adults living in nursing homes, looking specifically at whether commonly used NAMs could influence how bacteria respond to antibiotics.

The focus on older adults is especially important. Seniors are among the most frequent users of both painkillers and antibiotics. Medications like paracetamol and ibuprofen are staples of elder care, often taken daily to manage chronic pain, arthritis, or post-surgical recovery. Over time, this regular use means gut bacteria are repeatedly exposed to conditions that may encourage antibiotic resistance. At the same time, age-related changes in immune function make older adults more vulnerable to infections, increasing the likelihood that antibiotics will be needed when illness strikes.

The connection between painkillers and antibiotic resistance carries consequences that extend past individual patients. As Dr Honeyman notes, “Beyond the human toll, antibiotic resistance is expected to strain global economies, potentially costing between $1 trillion and $3.4 trillion annually by 2030 due to increased healthcare expenditures and lost productivity.”

While the financial burden of antibiotic resistance is often discussed at a global level, many of its consequences emerge in everyday care settings. In long-term care facilities where residents live in close quarters and share common spaces, the combination of frequent painkiller use and antibiotic exposure can be especially risky. If everyday medications are quietly nudging bacteria to become more resilient or adaptable, the result may be repeated infections, harder-to-control outbreaks, and fewer effective treatment options when they’re needed most.

And this concern isn’t limited to senior communities. Across the wider population, non-antibiotic medications are used at a massive scale, often without a second thought. While these drugs aren’t the primary drivers of antibiotic resistance, the findings suggest they may accelerate bacterial changes that make infections harder to treat once antibiotics are eventually needed.

What Experts Recommend

So should you swear off painkillers and muscle your way through the next headache? Experts say no. “Researchers are not advising people to immediately stop using painkillers,” explains Dr Honeyman. “But it is important to regularly review medications.” 

In practice, this means treating pain relievers like any other medication: not a daily default, but an option used at the lowest effective dose, reassessed over time to make sure it’s still necessary. These reviews are especially important in long-term care settings such as nursing homes, where residents often take multiple medications at once. 

Deprescribing, when appropriate, can help to reduce unnecessary drug exposure that may place stress on gut bacteria and quietly encourage resistant behavior, Dr Honeyman adds.

Safeguarding against antibiotic resistance also requires careful antibiotic use. Experts continue to stress that antibiotics should be reserved for confirmed or strongly suspected bacterial infections, and only under the guidance of a healthcare provider. Avoiding self-medication or leftover prescriptions helps prevent the low-level drug exposure that gives bacteria opportunities to adapt.

Looking ahead, the future of prescribing will likely move beyond evaluating drugs in isolation and closer toward understanding how everyday medications interact within the body’s internal microbial environment. This broader perspective supports smarter prescribing, more thoughtful medication use, and better long-term protection against antibiotic resistance, without requiring patients to compromise on effective pain relief.