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expert reaction to UNEP report on environmental dimensions of antimicrobial resistance

The UN Environment Programme (UNEP) has published a report on environmental dimensions of antimicrobial resistance (AMR).

 

Dr Chris Connolly, Independent Scientist, The International Union of Basic and Clinical Pharmacology (IUPHAR), said:

“This is a very important report that highlights an underappreciated danger from surplus antibiotic present in the environment after medicinal and agricultural use. It reports that antibiotic resistance may be developing within microbes in the environment. Importantly, the environmental contribution to this major threat to human health may be much larger than anticipated. Finally, the report recognises the need for a ‘One Health’ response where reducing the environmental load is the key to controlling this growing threat.

“In addition to secondary contamination, chemicals with anti-microbial properties are also released directly into the environment (eg. fungicides and sewage used on crops). The problem of antibiotic resistance mirrors the concurrent development of pesticide resistance in crop pests, where options may also become restricted.

“A key point made is that our understanding of the impact of antibiotics on biodiversity, and consequently on ecosystem functions, is the need to monitor environmental contamination from all sources. This doctrine should be expanded to include all chemicals found in the environment (eg. medicine, veterinary medicine, agriculture, industrial chemicals and algal bloom toxins).

“However, to be scientifically credible, monitoring needs to be expressed in terms of bioactivity (for multiple bystander species) rather than by the weight of chemicals applied/detected. The weight of chemicals required decreases as more highly potent versions are developed but the level of bioactivity and toxicity may be rising. By expressing contamination as bioactivity levels, it will be easier to pollution levels to biological threat (eg. loss of bees and beneficial microbiomes) or to the selective pressure on resistance in pathogenic bacteria).

“Only with knowledge on bioactivity (pharmacology) could we hope to understand the threats from polypharmacy (exposure to chemical cocktails). A pharmacological understanding of drug action is used in medicine to dose patients with the appropriate drugs needed, while avoiding unacceptable side-effects. Maybe it’s time we treat the environment as a patient in poor health.”

 

Dr Lindsey Ann Edwards and Professor Debbie L Shawcross from King’s College London, said:

For five thousand years, the size and vitality of cities, economies, and empires were determined by infectious diseases. In the past centuries, unprecedented technological and medical revolutions had allowed humanity to free itself from the grip of epidemic cycles. Antimicrobials have been essential in reducing the burden of infectious diseases in humans, animals and plants. The two leading killers worldwide at the start of the twenty-first century were heart attacks and strokes and infections were in decline. However, antimicrobial effectiveness is now in jeopardy because several antibiotic, antiviral, antiparasitic and antifungal treatments no longer work because of antimicrobial resistance (AMR).

“The Lancet published in 2022 that Drug-resistant infections are now once again a leading cause of death worldwide. The Covid-19 pandemic is a terrible reminder that our victory against infection is far from complete. Today the United Nations Environment Programme published a report that states that “The climate crisis” and AMR are intimately linked and “two of the greatest and most complex threats the world currently faces. Both have been worsened by, and can be mitigated by, human action”. “To reduce superbugs, the world must cut down pollution”.

“The triple planetary crisis entails higher temperatures and extreme weather patterns, land-use changes that alter its microbial diversity, as well as biological and chemical pollution. All these contribute to the development and spread of AMR.

“We are in full support of playing our part in implementing the report’s comprehensive set of global solutions. This encompasses the strengthening of environmental action in the ‘One Health’ response to AMR which will not only help reduce the risk and burden of AMR on societies but will also help address the triple planetary crisis. The time to act is now!”

 

Professor Till Bachmann, Deputy Head of Infection Medicine & Personal Chair of Molecular Diagnostics and Infection, University of Edinburgh, said:

What does the report tell us?

“There is a huge problem already today (‘4.95 million deaths worldwide were associated with bacterial AMR in 2019’) in relation to drugs to treat infectious diseases and it is expected to rise significantly in the future (‘by 2050 up to 10 million additional direct deaths’). When these drugs don’t work anymore it is called Antimicrobial Resistance (AMR). This is a problem usually associated with human medicine but also strongly considered in veterinary medicine. Increasingly, it is understood that the environment plays a big role in this. The main human contribution to AMR through the environment is through taking antibiotic drugs (what goes in, comes out again), run off from pharmaceutical manufacturing, and veterinary/agricultural use of antibiotics. The concept which factors in human, animal and environmental sector to research and tackle AMR is called ‘One Health’. Traditionally, the environmental sector has been underrepresented in this discussion. The new UNEP report will help raising the profile of the environment in this discussion.

“Organizations tackling AMR across the globe are increasingly putting One Health at the forefront of their strategies (see https://www.jpiamr.eu/activities/one-health-amr/, I am chair of the JPIAMR SAB) , The UNEP report strongly links the AMR problematic to the ‘triple planetary crisis’ (climate change, pollution and biodiversity loss). Climate change and pollution facilitate the emergence of AMR and antibiotic overuse facilitates biodiversity loss (e.g. in the human gut) which in turn facilitates AMR. All these together have a high risk to make infectious diseases worse for humans, animals and plants, i.e. more diseases, less/more expensive food.

“The report describes a range of actions to tackle AMR from an environmental perspective which include stronger international collaboration, stronger implementation of rules and regulations, much stronger focus on prevention (e.g. through the well-known WASH concept (water, sanitation, hygiene)), awareness raising and stronger financial incentives to fund and invest in alternative strategies with less impact on AMR.

How does this report collate all the evidence on the environmental dimensions of AMR?

“Through consultation with experts from the field (existing evidence, i.e. what is already known) and in close collaboration with the other UN Organizations which are part of the Quadripartite (‘This report reviews the available evidence on environmental dimensions of AMR. It was prepared through a consultative and extensive review process that engaged more than 50 experts and stakeholders from countries around the world, including from the Quadripartite organizations: the Food and Agriculture Organization of the United Nations (FAO), the United Nations Environment Programme (UNEP), the World Health Organization (WHO) and the World Organization for Animal Health (WOAH)’)

Is there anything new this report can tell us?

“It seems that the report has collated what was already known and combined it into the presented document. As far as I can see, there were no new data generated but the value lies in the integrated presentation. The report highlights key areas of emerging attention including the link to climate change, pollution and biodiversity loss as well as including plants/crops and other pathogens than bacteria into the consideration such as fungi.

Does this report suggest there any changes in consensus on AMR?

“The environment traditionally tends to be a relatively neglected area in the field of AMR. This report helps raising the profile as core component of the One Health concept (human + animal + environment) and links it with the ‘triple planetary crisis’ (climate change, pollution and biodiversity loss).

Any other comments on the report or its implications?

“In short, the report excellently shows how ‘everything is connected’. Human actions have consequences and do backfire. There is a long-term accumulation of small problems which already today lead to substantial problems around the world (‘the silent pandemic’) but are likely to get worse through the contribution of other crises the world is facing. A holistic approach and global collaboration and local action is needed to tackle AMR – as outlined by the UNEP report.

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“The publication of the UNEP Report ‘Bracing for Superbugs: Strengthening environmental action in the One Health response to antimicrobial resistance’ sends a strong message. The report is a powerful collection of overwhelming evidence that AMR needs to be tackled in a One Health context – human, animal and environmental domains together. It rightly urges that we factor in the interdependencies with the triple planetary crisis of climate change, pollution and biodiversity loss. I am delighted to see strong representation of diagnostics and surveillance throughout the report. Rapid on-site diagnostics and detection of antibiotic residues, AMR or pathogens – like the tests we are developing in the DOSA project – have a strong contribution to make in tackling AMR in the environment as well as human and veterinary medicine. For example, a diagnostic test done in primary care or on farms can help reducing antibiotic use and the demand for antibiotic manufacturing and thereby help reducing the discharge of antibiotic residues into the environment altogether. In turn, diagnostics and detection done in the environment can inform practises in the human and veterinary sector.”

 

Dr Sam Willcocks, Lecturer in Biosciences, Brunel University London, said:

The United Nations Environment Programme report rightly shines a light on the importance of environmental pollution in driving, sustaining and spreading antimicrobial resistance (AMR). In recent years, the threat of AMR to our modern way of life has been championed by countries such as the UK and has gained prominence at the highest level, including at the United Nations. This has resulted in many countries signing up to so-called ‘National Action Plans’ to tackle AMR through multi-faceted approaches and agreeing to ongoing surveillance and scrutiny of their efforts. Until now, however, the focus has been on the health sector and in agriculture. The living and non-living environment can be considered the ‘missing link’ that connects these two with wider aspects including climate change, sanitation and industry. There is consensus in modern research that the state of the microbial world around us can directly affect human health, and is in turn directly affected by our activity. Together, we call this the ‘One Health’ paradigm. In this context, the UN report is a welcome spotlight on the issue that should encourage individual countries to co-ordinate efforts to implement their recommendations. In the absence of any legislative framework, however, its success will be limited by the willingness of countries and the private sector to undertake these changes voluntarily.  

 

Dr Shan Goh, Senior Lecturer in Microbiology, University of Hertfordshire, said:

“This comprehensive report is impressive in scope and depth, it has left no stone unturned and has addressed the complex problem of AMR in One Health, with a focus on drug-resistant bacteria, by gathering evidence in relevant literature spanning microbiology, human science, animal science, plant science, environmental science, pharmaceutical science, medicine, economics, and probably a few other areas I have missed. Although the focus is on the environmental component of One Health, it being the most overlooked of the Human-Animal-Environment circle, because these three dimensions are interconnected, all subject groups related to environmental health had to, and was rightly, scrutinized. Evidence has been analyzed by experts in respective fields and importantly, connections have been made between relevant strands to synthesize a coherent and insightful roadmap of what needs to be done to reduce AMR and protect ourselves from the dire situation of triple planetary crisis that we are heading towards. The report has strengthened previous acknowledgements of the environment being a source and a sink for AMR, hence current practice in contamination and adding to the sink is unsustainable and hazardous to living organisms. The novelty of the report is in its recommendations on managing this complex situation from multiple angles (“systems approach”) and with options on “comprehensive” or “minimum strategy” because it acknowledges that there is no “one size fits all”, particularly for low/low and middle-income countries who are disproportionally affected by AMR. Another important aspect that this report addressed was gender equality, where there is evidence that AMR disproportionally impacts women in some situations, but there are gaps in knowledge that the report has encouraged to investigate. This report has clarified the responsibilities of governments, sectors, and citizens. There is much to be done and a concerted effort is the only way forward to tackling AMR.”

 

Prof Mathew Upton, Professor of Medical Microbiology, University of Plymouth, said:

“The report covers the need to regulate and monitor antimicrobials in the environment from the point of manufacture all the way through to use in humans and animals and on into our waste streams that contain antimicrobials that we consume or dispose of inappropriately. Environmental pollution with antimicrobial-containing waste is a key risk driving the selection of future-resistant bacteria and fungi. Also discussed is the need to support and incentivize good practice in the manufacture, sales and use of antimicrobials to reduce environmental exposure.

“One area where antimicrobial use has a direct impact on the environment is in farming. Although the situation is improving in some parts of the world, vast amounts of antimicrobials are used to treat and prevent infections in food animals. The report describes how improved husbandry and other infection prevention and control methods like vaccination should be used to reduce infections and the need for antimicrobial use, which in turn limits environmental pollution with antimicrobials, antimicrobial residues and resistant microbes. This is particularly applicable in aquaculture, which is going to be a major source of aquatic protein by 2050.

“This is a very timely report and it is encouraging to see the focus on the environment as we can only have a genuine chance of addressing the global threat of AMR by working together in human, animal and environmental settings and much previous attention has been directed at AMR in animals and humans. AMR is such a complex problem that interlinks all these settings, with human or animal activity and antimicrobial consumption directly impacting the environment where selection for resistance happens. Resistant bacteria or fungi (or parasites) in the environment are then picked up by humans or animals, which can then result in drug-resistant infections; the environment is key to development and transmission of AMR.”

 

Dr Lisa Avery, Senior Environmental Microbiologist at The James Hutton Institute, said:

“This report explains the role the environment plays in the development of AMR. The environment can act as a mixing pot of chemicals that drive antimicrobial resistance and microorganisms that can acquire that resistance. As humans and animals then come into contact with these resistant organisms, some could cause diseases for which our treatments no longer work.

“As someone working in this field, the report doesn’t tell us anything new. But by collating existing evidence, it shows that we need to be tackling the environmental dimension of AMR. The role of the environment has tended to be neglected in favour of a focus on human and veterinary medicine and prescribing. This report makes it clear that AMR in the environment must be addressed.

“The report highlights particular activities such as sewage and industrial wastewater release and run-off from agriculture that increase the number and frequency of resistant organisms in the environment. The risk to human health depends on exposure. Although we do not yet understand exactly how AMR in the environment translates into antimicrobial-resistant infections in humans or animals, the pathways are there. If we wait to act until we fully understand the relationship, we risk undermining the effectiveness of the antimicrobial medicines we rely on.

“The report usefully emphasizes that tackling the human activity that drives other planetary crises can also mitigate AMR spread. For example, measures that protect biodiversity, such as reducing pollution of watercourses, could also reduce the development of AMR in those water courses. But it’s important to be clear that AMR is also a naturally occurring phenomenon. What is important to understand is “How much AMR in the environment is too much?”. The development of environmental standards for monitoring of AMR, mentioned in the report, is key to this.”

 

Dr Andrew Singer, a Senior Scientist at the UK Centre for Ecology & Hydrology, said:

“The UN report provides a holistic perspective on the environmental dimension of AMR. It is quite possibly the most comprehensive report of its kind. It restates the importance of addressing the drivers of AMR in the environment using the most recent of academic studies from the literature. In short, it confirms that, globally, the environmental dimension of AMR has not been a priority for national AMR action plans. The delay in integrating the environment into national action plans is a serious one, which will have economic as well as human life consequences. The report makes the case that sufficient evidence exists in the literature for demanding greater action and that the long-term costs of inaction will greatly exceed the short-term cost of action.

“The many authors conducted a literature review, focusing primarily on recent academic papers in the area of environmental AMR. They appear to have consulted with additional scientists in the field and relevant stakeholders, including environmental regulators across many countries.

“For those who have been embedded in the field, there is nothing terribly new to this report other than it is a hugely comprehensive and a holistic summary of the problem. There is a recognition that wastewater surveillance, as developed during the COVID-19 pandemic, could become a useful tool for developing a global monitoring network for antimicrobials, antimicrobial-resistant microorganisms, and antimicrobial-resistance genes.

“Perhaps the best way to view this report is that it is trying to present a rationale for action with respect to the environmental dimension of AMR—which the authors hope translates into a more purposeful and thorough integration of the environment in governmental planning and national action plans. The authors call to maintain a holistic understanding of the interconnectedness of many sectors of society as well as the world—and that any mitigations that are put in place must be designed in recognition of these local, regional and international connections. For example, international travel and commerce has shown itself time and time again as being one of the most important vehicles for the global spread of AMR, whether it be by means of a pathogen in a human’s gut or a pathogen that was found in the sewage-contaminated sea and was subsequently ingested into the ballast tank of a supertanker that travels across the globe, depositing this contaminated ballast water in each port it reaches.

“It is hopeful that governments will respond to this report by taking seriously the call for integration of the environmental dimension into the national action plans and the need to have a holistic vision of addressing the many drivers of AMR, whether it be from combined sewer overflows laden with antimicrobial-resistant bacteria contaminating a river, to importing fish grown with the obligate use of several antimicrobials, to the challenge of using antifungals in crops that drive fungal pathogens to become resistant to treatment in the clinic.”

 

Prof Oliver Jones, Professor of Chemistry at RMIT University in Melbourne, Australia, said:

“This comprehensive, well-written, and very welcome report on the issue of environmental pollution from antimicrobial compounds. 

“Science has known for some time that the effectiveness of antimicrobials is waning as things bacteria, viruses, and even parasites and fungi, have become resistant to existing treatments. What has not perhaps yet sunk into the public consciousness is just how big a problem this could be for society in the very near future, in terms of both human health and effects on agriculture, so it is really good to see this topic getting some attention.

“We tend to think of antibacterial resistance as being a problem associated with hospitals. What this report shows is that antibiotics and other medications ending up in the environment is a major factor in the spread of antibiotic resistance and something we need to pay attention to sooner rather than later.

“This is obviously a sensitive subject given human health is generally given priority over environmental concerns. Drawing expertise from scientists all over the world the report this report does an admirable job of breaking down the science into understandable conclusions and making sensible suggestions about actions we could take to try and reduce potential future impacts from pharmaceutical pollution on our health and food systems, which is something we haven’t often seen before).

“If we are going to address the problem of antibiotic resistance, we need to know the full range of sources of the issue and their relative risk. This report is a welcome step in that direction”.

 

Dr Simon Clarke, Associate Professor in Cellular Microbiology at the University of Reading, said:

“This detailed and timely report highlights the close connections between damage to the environment and future risks to human health from new superbugs that could be potentially deadly to humans.

“When we think about pollution, many people think about plastic in the ocean or fumes from cars and factories. But this report highlights that the pollution we can’t see in water, soil and air is potentially more damaging. This can be both from antimicrobial resistant bugs seeping into rivers from badly treated sewage, or from chemical spills that cause mutations in naturally occurring communities of microbes. 

“This report highlights not only the scale of the problem, but the many actions the world needs to take to reduce the risk of a worst-case scenario in which 10 million people die each year by 2050 from untreatable infections. Many of these actions come hand in hand with developments to tackle the climate crisis and biodiversity loss. They will also provide millions of people with cleaner water to drink and bathe in, and protect animals and plants including those we rely on for food. And crucially, as the Covid-19 pandemic reminded us, we need to act globally to keep our own nations and families safe.

“Because of the effectiveness of antibiotics, we have perhaps forgotten the deadly impact that many infections had in the past. The risk of doing nothing is that every injury, operation or routine trip to hospital comes with the risk of picking up a lethal infection.”

 

Dr Catrin Moore, Senior Lecturer, St George’s, University of London, said:

“The report highlights the importance of environmental factors in the spread of resistant pathogens and further highlights the need to have a multi-sectoral response to combat AMR.

“This report assimilates evidence from the scientific community – both manuscripts and expert elicitation in addition to policy reports and evidence from Quadripartite organizations in a consultative review process. It is an encompassing report calling for priority action to address key pollution sources from all sectors (environment, aquaculture, animal, plants and human sectors). It calls for an increase in global efforts to improve integrated water management and promote water, sanitation and hygiene to limit the development and spread of AMR in the environment. It asks for international standards to be established and to have an understanding of good microbiological indicators of AMR from environmental samples – this information can be used to guide risk reduction decisions and measure potential interventions to reduce AMR.

“This report highlights the mounting evidence environmental drivers play in the development, transmission and spread of AMR, including back to humans and animals. The report describes the anthropological nature of AMR and links the challenges to the triple planetary crisis of climate change, biodiversity loss and pollution and waste, which are all driven by human activity.

“While the report doesn’t suggest any changes in consensus on AMR in my view, it does remind us that more action is needed, and that environmental regulators should strengthen the framework to protect the environment from AMR and antimicrobial pollutants. Antimicrobial pollutants (and the degradation of antimicrobials in the environment) and their selective pressure on microorganisms increasing the levels of resistance are often forgotten.

“This report reminds me that high levels of AMR could ultimately be on my doorstep, and in the water that I swim through with untreated human waste being released into local waterways. Although the highest burden of AMR is found in low- and middle-income countries, and resistant bacteria can be spread easily – they show no respect to country borders. Ultimately if resistant pathogens are increasing in my local environment, reducing the burden of mortality and morbidity due to AMR will be an impossible task.”

 

 

Bracing for Superbugs: Strengthening environmental action in the One Health response to antimicrobial resistance’ was published by UNEP at 14:30 UK time Tuesday 07 February 2023.

 

 

Declared interests

Dr Lisa Avery is a senior environmental microbiologist in The James Hutton Institute’s Environmental and Biochemical Sciences group and leads the Centre for Human and Animal Pathogens in the Environment (HAP-E) – a cross-institute interdiscpilinary hub drawing together those working in this field. She completed a PhD in environmental microbiology in 2001 at the University of Nottingham and worked at Bangor University and Cranfield University prior to taking up her post in catchment microbiology at the Macaulay Institute, now part of The James Hutton Institute, at the end of 2006. In 2011 she joined the James Hutton Institute where she works primarily on prevalence and transport of pathogens and antimicrobial resistance (AMR). She also has expertise in water and waste treatment and reuse, in particular the use of low-tech systems in the UK and developing countries.

Prof Mathew Upton: “my research is focused on antibiotic discovery programmes and I have collaborative projects in vaccine development for use in agriculture and previous research interests in transmission of resistant bacteria.”

Dr Andrew Singer: “I have no COI in relation to this topic.”

Prof Oliver Jones: “I don’t have any conflicts of interest to declare, although I did do my PhD on the topic of pharmaceutical pollution in the environment.”

Dr Simon Clarke: “No DoIs to make.”

Dr Shan Goh: “I have no conflict of interest.”

Professor Till Bachmann: “Chair of Scientific Advisory Board of the Joint Programming Initiative for AMR

Judge for Longitude Prize on Antibiotics

AMR Strategy Lead Edinburgh Infectious Diseases

Chair Edinburgh AMR Forum

Director Fleming Fund Fellowship Scheme for Edinburgh Infectious Diseases

Coordinator DOSA – Diagnostics for One Health and User Driven Solutions for AMR project https://dosa-diagnostics.org/

Partner VALUE-Dx Innovative Medicines Initiative project

Advisor (current) CARB-X, Sefunda AG”

For all other experts, no reply to our request for DOIs was received.

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