In a Ukrainian hospital, wounded soldiers languish with stubborn bacterial infections. In Liberia, a young mother's surgery wound refuses to heal after a C-section. Superbugs hiding in eyedrops imported from India cause multiple deaths and many more cases of blindness.

Worldwide, the toll of drug-resistant infections has only been growing. A study published last year found that 1.27 million people died in 2019 from infections resistant to antimicrobial drugs. The annual death toll could reach 10 million by 2050, according to the United Nations.

Now a new study highlights a surprising potential vector for the spread of antimicrobial resistance (AMR): air pollution.

"Airborne fine particulate matter, we usually call it PM2.5, contains a cocktail of microorganisms," says Hong Chen, professor of environmental engineering at Zhejiang University and corresponding author of the study.

It has long been suspected that particulate air pollution could transport antimicrobial-resistant bacteria that leak into the environment from farming, aquaculture, wastewater treatment and hospitals. The new research, from a team at Zhejiang University in China and the University of Cambridge in the United Kingdom, set out to quantify the role of air pollution in the growing global AMR problem. The team found a strong association between particulate air pollution [in a given country and reports of clinical antibiotic resistance.

Using data from published studies as well as disease surveillance networks, clinical trials and diagnostic labs, the researchers tried to untangle which factors were most important in driving up global antimicrobial resistance over the period from 2000-2018 (CQ). Ultimately, they say the air pollution association accounts for some 12% of the increase during that time, adding up to 480,000 premature deaths and economic costs of $395 billion in 2018 alone.

"The analysis suggests that PM2.5 is one of the leading factors driving clinical antibiotic resistance," says Chen.

Drug-resistant bacteria in the soil, in water, in sewage

Drug-resistant microbes multiply when a course of medication, such as an antibiotic, kills off susceptible bacteria and spares the few who happen to be hardier. Those resistant bacteria are then free to thrive and spread.

Widespread use of antibiotics in human health care, as well as in animal farming and aquaculture, deposit lots of resistant bacteria in the soil, waterways and sewage treatment facilities. Also mixed in with the microorganisms is free-floating genetic material, including some that carry genes for resistance to antimicrobials. Those genes can spread resistance on their own as bacteria take up the DNA from their environment, swap genes with other microorganisms or pass the resistant genes along through viruses.

Ultimately all that material doesn't stay in the soil or the waterways but catches rides on particles and aerosols into the air, where people can inhale them.

The remaining particles "can then return to the earth's surface through deposition in snow and rain, connecting the atmosphere and the earth's surface and creating a global [antimicrobial resistant gene] cycle," says Chen.

Investigating the link between air pollution particles and antibiotic resistant microbes

The scope of the new study is unprecedented, researchers say: "This study is the most comprehensive analysis of the burden of AMR to date, producing estimates for 204 countries and territories, 23 bacterial pathogens, and 88 pathogen–drug combinations."

The study reveals that low-income regions tend to face higher burdens of both pollution and antimicrobial resistant infection, with sub-Saharan Africa the most affected, followed by south Asia.

The study nails down an association between particulate air pollution and AMR, but the researchers say it does not establish causality or reveal the biological mechanism at play. Elena Buelow, a postdoctoral researcher at the University of Grenoble Alpes in France, says it's an important relationship to probe, but she's yet not convinced that air pollution is the ultimate culprit.

"I would be careful to draw conclusions on the causal relationship," says Buelow. "There's an increase in antimicrobial resistance in the past 20 years. There's an increase in pollution in the past 20 years. There's also an increase in population growth in the last 20 years. There's a strong correlation, and we have to continue to study this. But I'm not sure we can conclude from this study that this is a causal relationship."

The researchers adjusted for other factors that could be affecting the rates of AMR, such as socioeconomic status, health expenditures and education. The air pollution link persisted, and in fact strengthened over time, they say.

For Buelow, it will be important to more firmly establish what the actual mechanism is for spreading AMR to actual people through the air.

"For bacteria, these [particles] are big islands. It's kind of fascinating that they attach to this tiny surface, and they can form little tiny multispecies colonies and be transported this way. That is true, but to what degree this causes carriage of antimicrobial resistant bacteria within individuals, we don't know that," says Buelow.

However, the authors concede that data is incomplete in many of those same regions, where disease surveillance systems tend to be more sparse. And Elena Buelow points out that the measurements used by various countries differ, making country-by-country comparisons difficult.

Another reason to curb air pollution

The link suggests that curbing air pollution could be another lever for controlling the spread of antimicrobial resistance (in addition to all the other downsides of particulates). The study calculates that bringing global air pollution down to the WHO's target levels by 2050 would cut global antibiotic resistance by 16.8% and avoid nearly one in four premature deaths attributable to AMR.

"This means if we can control PM 2.5, then we can have a twofold result," says Chen.

Elena Buelow agrees that studies like Chen's can help us see the problems holistically.

"This is all correlated and it's important to bring awareness to that so that people and policymakers are woken up."