A study suggests that the rise of antibiotic resistance is linked to contamination

The rise of antibiotic-resistant microbes has put the world in jeopardy: superbugs already kill more than AIDS, malaria and some cancers. And the outlook in the short and medium term is not very encouraging. The World Health Organization (WHO) considers this phenomenon “one of the greatest threats to global health” and points to the improper and excessive use of antibiotics as an accelerator of these resistances. The inappropriate consumption of these drugs is under scrutiny, but it is not the only cause under study. New research, published Monday in The Lancet Planetary Health, has also found a correlation between antibiotic resistance and pollution: the more air pollution, the more resistance.

But the authors admit that their findings are only an association, causality cannot be established, and the exact mechanisms explaining this relationship are also unclear. The researchers defend, yes, that reducing air pollution levels could help reduce resistance to antibiotics and project that, if the WHO air quality guidelines are met, by 2050 these could be reduced by 17%. resistors.

Humans are exposed to superbugs through food or through direct contact with infectious sources, such as animals. Also by water, soil or air. “For example, resistant bacteria in hospitals or in livestock could be transmitted to water treatment facilities or ecosystems, and even be emitted from these environments into the atmosphere and exposed to humans through inhalation,” they exemplify. the authors in the article.

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Regarding the air, which is a vector for the dissemination of these resistances, the researchers focus in this study on one of the main pollutants, which are PM2.5 fine particles: “It has been shown that they contain various resistant bacteria and genes of resistance to antibiotics, which are transferred between environments and humans inhale them directly, causing respiratory tract lesions and infections”, they justify.

Based on this premise, they analyzed the available data from 116 countries between 2000 and 2018 —nine pathogens and 43 drugs were analyzed— and found that air pollution levels correlate with greater antibiotic resistance. For example, a 1% increase in PM2.5 was associated with a 1.49% increase in the resistance of Klebsiella pneumoniae bacteria to carbapenems, which are a type of broad-spectrum antibiotic. “Globally, a 10% increase in PM2.5 per year could lead to a 1.1% increase in aggregate resistance to antibiotics and 43,654 premature deaths attributable to antibiotic resistance,” they state in the article. The research concluded that antibiotic resistance stemming from PM2.5 fine particles caused around 480,000 premature deaths in 2018 worldwide.

“The main mechanism is that the high concentration of PM2.5 transports more antibiotic-resistant bacteria and genes”

Zhenchao Zhou, Universidad de Zhejiang

The authors also found differences by region. Africa and Asia are the areas where the increase in PM2.5 could cause the greatest increase in antibiotic resistance: in Saudi Arabia, for example, researchers calculate that a 10% increase in PM2.5 would imply a 3% increase in bacterial resistances.

The researchers believe that reducing air pollution can have a double advantage, as it can also prevent the harmful effects of poor air quality. The study modeled several future scenarios based on the fluctuation of several variables, such as air quality, health spending or the use of antibiotics. And he concluded that, if nothing is done in the coming decades (until 2050), resistance to antibiotics will increase by 17% and deaths attributable to this cause will grow by more than 56% globally —and, especially, in the Sub-Saharan Africa. If, on the other hand, PM2.5 is controlled at 5 μg/m³ —the threshold recommended by the WHO— global resistance to antibiotics could be reduced by 16.8% and prevented 23.4% of attributable deaths to this phenomenon in 2050.

The mechanism is not clear

The researchers admit limitations in their research. Starting with the data, since some countries did not provide all the necessary information and these deficiencies may influence the final results. They also state that there may be other factors that are inducing this resistance to antibiotics: “Additional social, economic and environmental factors must be introduced to comprehensively assess the association with antibiotic resistance, such as food intake, the use of veterinary antibiotics , exposure to other pollutants, extreme environmental events, habits and customs”; pick up the item.

The other big pending question, they assume, is that “the underlying mechanism of air pollutants affecting antibiotic resistance is still unclear and more medical evidence is still needed to verify this fact.” Zhenchao Zhou, a researcher at the Faculty of Environmental and Resource Sciences at Zhejiang University (China) and first author of the study, acknowledges the limitations and, in an email response, specifies: “We all know that correlation does not represent causation, and for the sake of rigorous science, we say that it ‘may be linked’. In our analysis, we could say that the correlation between air pollution and antibiotic resistance is strong and significant.”

“It was already known that elements related to antibiotic resistance could travel in airborne particles, but this is an interesting message”

Juan Pablo Horcajada, Hospital del Mar in Barcelona

Regarding how this relationship between contaminating particles and antibiotic resistance is explained, Zhou explains that, indeed, the “exact mechanism is not clear.” He adds: “According to reports from the existing literature, the main mechanism is that high PM2.5 concentrations carry more antibiotic-resistant bacteria and genes, and direct exposure to these substances can lead to increased antibiotic resistance. in the population”.

Zhou also recalls that it has already been shown that PM2.5 particles “could increase the permeability of the cell membrane to improve the efficiency of horizontal gene transfer, accelerating the evolution and exchange of antibiotic resistance elements in bacterial pathogens”.

More questions than answers

About five years ago, he says, he and his team collected about 100 PM2.5 air samples from hospitals, farms, and cities, and sputum samples from human respiratory tracts, and “surprisingly,” he admits, they found “that the abundance of antibiotic resistance genes in airborne PM2.5 was very high.” And those airborne antibiotic resistance genes, he explains, were going to be directly exposed to the human body. “We found that outdoor and indoor PM2.5 particles together contributed to 7% of antibiotic resistance genes in the airways of hospital patients, suggesting an important exchange between the air and human commensals. So we hypothesized that PM2.5 would affect antibiotic resistance, but at the time we didn’t know what kind of impact. Now, using big global data, we confirm that PM2.5 has a significant impact on antibiotic resistance”, he relates.

Juan Pablo Horcajada, head of the Infectious Diseases service at the Hospital del Mar in Barcelona, ​​describes this research as “innovative and provocative”, although he admits that it involves “correlations and deductions of data from very different databases”. “It was already known that elements related to antibiotic resistance could travel in airborne particles, but this is an interesting message,” he says. The infectologist argues that, if a causal relationship between contamination and antibiotic resistance is confirmed, the future impact of resistant microbes may be even greater than expected. “Antimicrobial resistance worries us a lot and is growing more and more. There are some bacteria that we no longer know what antibiotics to treat with. It is very worrying because (this phenomenon) is in hospitals, primary care and veterinary medicine ”, he explains.

Speaking to the Science Media Centre, Kevin McConway, Emeritus Professor of Applied Statistics at the Open University in the UK, cautions that the results of this research “require great care in interpretation” and notes that while the authors found “correlations and interesting associations”, “doubts remain about cause and effect”. McConway, who has not participated in the research, points out that the data is from entire countries, but within the same region there can be a lot of variability, for example, in air quality and the average results may not represent what what happens in general

The expert also warns that “it is likely that there are other possible confounding factors on which they could not collect any data and it is still possible that there are confounding factors at work and that these are involved in the causation of the level of resistance to the antibiotics of a country”. And he insists: “Overall, this analysis of observational data and modeling research indicates that the role of air pollution in relation to antibiotic resistance might well be worth looking into further, but at this stage there remains great uncertainty about what is really happening. He would say that the new research raises more questions than it answers.”

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