Introduction
The sixth edition of the Environmental Dimension of Antibiotic Resistance symposium was held in Gothenburg, Sweden, from Thursday, the 22 of September to the 27th after two postponements due to the coronavirus pandemic. It is part of a series of conferences, the largest scientific meetings that address the environment's role in antimicrobial resistance (AMR).
The Centre for Antibiotic Resistance research (CARe) organised the conference with sponsorship from the city of Gothenburg, the University of Gothenburg, the region of western Sweden, and the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR). Prof. Joakim Larsson chaired the hybrid event with over 50 online and 250 physical attendees from 41 countries.
Highlighted below are some of the interesting presentations made:
The first day started with a keynote speech titled “Interesting Compounds From Microbiome Mining” by Prof. Kim Lewis, Director of the antimicrobial discovery center at Northeastern University. He takes advantage of the environment as a source of novel antibiotics. His famous discovery of teixobactin was only possible because he and his team figured out how to cultivate environmental bacteria that was not possible previously and limited our ability to understand the role of the environment in the development of antimicrobial resistance.
The speech covered the history of antibiotic discovery and how the probability of discovery has reduced with time - advanced technology approaches working better for cancer and heart disease therapies but not antibiotics. For the study, they decided to explore uncultured bacteria in the environment and learned how to cultivate them. Part of this included making an advert on craigslist paying people to send a soil sample from their backyard. They realized that there are still more compounds with antimicrobial properties yet to discover in nature.
After the keynote speech, we received a welcome note from the deputy Lord mayor, Pär Gustafsson, and Regional council President, Annika Tärnström.
We then listened to a digital presentation by Andrea Hinwood, a chief scientist from the United Nations Environment Programme (UNEP) who joined us from Nairobi, Kenya. She shared a status report on AMR from the United Nations Environment Programme after the environmental dimension of AMR was recognized as an issue of concern in the UNEP frontiers 2017 report. UNEP is working to provide science-based evidence that can inform strategies on AMR, ensuring that the environmental dimensions are reflected adequately in the one health response to AMR. She highlighted the work currently being done to raise awareness of environmentally persistent pharmaceutical pollutants (EPPPs); the need for sustainable food systems; pesticides, waste, and wastewater management, which form a nexus for antimicrobial resistance. UNEP is educating people on AMR - specifically targeting policymakers and environmental practitioners, supporting the government of India in the new National Action Plan on AMR preparation, and creating a database of experts in different regions. The UNEP is partnered with the World Health Organisation (WHO), World Organisation for Animal Health (OIE), and Food and Agriculture Organisation (FAO) to form a quadripartite collaboration for one health response to AMR. This collaboration is part of a one health joint action plan which involves:
Enhancing capacity to strengthen health systems
Reducing the risk of emerging and re-emerging zoonotic epidemics and pandemics
Controlling and eliminating endemic zoonotic, neglected tropical and vector-borne diseases
Strengthening the assessment, management, and communication of food safety risks
Curbing the silent pandemic of AMR
Integrating the environment into one health
Finally, she talked about a spotlight report on the environmental dimensions of AMR that should be published soon. Some actions identified for reducing the risk of AMR include assessment, regulation, industry action and partnerships, planning, monitoring, financing, and unused antimicrobials collection and management systems.
On Friday, Connor Brown, a Ph.D. candidate from Virginia Tech in the United States, made a presentation titled Development And Application Of MobileOG-db, A Unified MGE Database And Ontology, For Tracing The Fate Of MGE-borne ARGs In Hospital Sewage.
It was about the MobilOG-db application, a new resource and potential upcoming tools centered on horizontal gene transfer, environmental microbiomes, and Mobile Genetic Elements (MGEs) that mediate horizontal gene transfer. They created mobileOG-db, a unified database for MGEs, due to the difficulty in working with MGEs in a very refined way. You can try to build your database from publicly available databases but are likely to get false positives because these tend to include antibiotic resistance genes and how messy biology is. MobilOG-db includes over 6000 manually curated protein families as MGE hallmarks; it retains the original database labels that allow us to look for the MGEs simultaneously. The application also allows us to look for antibiotic resistance genes associated with the different types of MGEs. Connor and his colleagues will be looking to integrate the application into tools for detecting horizontal gene transfer in the future.
The following day, we had a presentation by Prof. Celia Manaia from Universidade Católica Portuguesa; titled Addressing Antibiotic Resistance Emissions In The Context Of Urban Wastewater Treatment. She shared some concerning facts: more than 45% of the global population are not connected to wastewater treatment, and 10% consume products irrigated by wastewater, the majority of these people are in developing countries. During the research, she analysed 195 wastewater treatment plants in different countries and found that membrane filtration technology was the most efficient but not the most popular. She also said that with current knowledge, it is impossible to establish antibiotic resistance limit standards but can recommend a minimum reduction percentage - possibly 1.5 - 2.0 log units of the indicator. The most common indicator species in wastewater treatment is Escherichia coli but unlike antimicrobial resistance, it is not found everywhere: so we could use antimicrobial resistance genes such as Int1 as an indicator. She recommended qPCR use in preference to metagenomics because it can target specific genes and facilitates integrated monitoring and data sharing. Antibiotic resistant bacteria are not the only pollutants in wastewater; this makes their removal a complex issue. Disinfection of biosolids is still a challenge witnessed by high costs and low returns.
We also had a presentation titled - Policy Levers To Address The Environmental Dimensions Of AMR by Prof. Sabiha Essack, a research chair in antibiotic resistance and one health at the University of Kwazulu-Natal in South Africa. Her presentation focused on policy levers to address the environmental dimensions of antimicrobial resistance. She talked about how India became the first country in the world to introduce regulations on pharmaceutical antibiotic pollution. The policy failed because of lobbying by the Indian drug manufacturers association regardless of the fact that the Union ministry of environment, forests, and climate change said it was due to limited research. These regulations covered most of the recommendations made by the UNEP.
Some of the policy levers she highlighted include procurement power, investor action, transparency, advocacy from Non-Governmental Organisations, leveraging other cognate issues to antimicrobial resistance such as climate change, behavioural change, and implementation research. We know what to do but have to make a behavioural change in our approach through implementation science which looks at the structure, culture, networks, and readiness for change within the implementing organisation. Policy success is contingent on; stakeholder ownership, enforcement capacity, substantive punitive action for non-compliance, trade-offs, alignment with other global issues, behavioural change, and implementation research approach.
Joakim Larsson's commentaries on this presentation agreed with what we already know: that the antibiotic pollution limits set by the antimicrobial alliance were not science-endorsed, lacked transparency, and were made by the pharmaceutical industry itself. The estimates made in the Wellcome Trust report, which analysed the economic impact of antibiotic pollution regulation on pharmaceutical industries, are based on interviews with the industry which generally overestimate costs when facing regulation.
On the fourth day, Luther King Abia Akebe from the antimicrobial unit of the university of Kwazulu-Natal, South Africa, made a presentation titled The afterlife resistome: Cemeteries as potential reservoirs and sources of multidrug-resistant pathogenic bacteria. He talked about how people in Africa, particularly in his locality, have high regard for their ancestors and therefore were displeased about him disturbing the cemeteries. He also highlighted how only conventional settings, such as wastewater, are currently considered when investigating the environmental dimensions of AMR, and issues like airborne AMR remain a relevant component but receive much less attention.
In his study, he made a soil and water analysis using collected soil and leachate samples from different cemeteries and microbial survival analysis by replicating cemetery conditions; it lasted six months. He examined leachate samples for antimicrobial resistance and pathotypes: and found that E. coli and a majority of the microbes were pathogenic, with 72% of isolates multidrug-resistant; found that the 2m soil samples have lower biodiversity than samples collected from lower depths. He noted that the hydrogeological conditions of an area should be considered when choosing a study site. In conclusion, Akebe and colleagues found that cemeteries are potential environmental reservoirs of antimicrobial resistant bacteria.
On the fifth day, Amy Pruden from Virginia Tech in the United States made a presentation titled Coordinating local and Global wastewater based surveillance of AMR: thoughts and considerations. Amy and colleagues proposed the water research foundation, after they asked for guidance in AMR monitoring. They submitted a successful proposal in 2019; in the following years, the coronavirus brought about the unprecedented collaboration of wastewater surveillance, so they took the opportunity to highlight its use in AMR monitoring. It became apparent that there was not one answer on what to monitor and therefore focused on four questions;
Monitoring ARB and ARGs circulating in the human population
Quantifying ARB and ARGs evading treatment
Quantifying ARB and ARG removal efficiencies
Assessing the evaluation of new resistant pathogens and mobile ARGs
As a method: they selected shot-Gun metagenomic sequencing because it is non-target but requires a high level of expertise and has high costs. There is a need to share surveillance data from different areas; this includes temporal data, temperature, latitude, and longitude. She highlighted the benefits of surveillance which include; identifying the hotspots for the evolution and spread of AMR, assessing treatments and interventions that most effectively mitigate AMR spread, and informing a risk assessment.
She made a special note on risk - the term used loosely and yet there are different types such as quantitative microbial risk assessment versus the evolutionary risk that apply to different situations.
The team from AMR Think-Do-Tank also made presentations - these are;
Mrs. Natukunda Michelle (AMR TDT)
Antimicrobial resistance as a precursor for microbial diversity loss at wastewater treatment plants
Microbial diversity, in particular, is vital to the functioning of all other organisms in the ecosystem. As urban areas expand, the production of wastewater increases, and its composition becomes more complex. Wastewater treatment processes such as activated sludge utilise microbes to break down organic matter and can have a microbial ecosystem with high diversity. Wastewater treatment plants are a necessary infrastructure, but inadequate treatment and disposal of wastewater are significant pathways for the environmental dissemination of antimicrobial resistance.
This review investigated how different wastewater treatment technology – namely: microfiltration, membrane bioreactor, chlorination, constructed wetland, biofilm, activated sludge, and sand filtration, act as a stressor for the selection of resistant microbes, bacteria in particular. Data were derived from journal articles of various wastewater treatment plant studies published between 2017 and 2022.
Findings show how conventional treatment technology like activated sludge removes the majority of susceptible bacteria but has little effect on the resistant microbes; this leaves room for them to thrive in the treated effluent and multiply in the environment. Traditionally designed to remove total coliforms, conventional treatment plants are not adapted to eliminating antimicrobial/antibiotic resistant bacteria. Resistant microbes evolved more to survive treatment processes. Overall, this study highlights the need for advanced wastewater treatment technology, such as microfiltration, capable of eliminating resistant microbes and thus preventing their proliferation into the environment.
Dr Jane Kengeya-Kayondo & Dr Arno Germond (AMR TDT)
Implementation Research - Bridging the "Know-Do" gap in Environment-driven Antimicrobial Resistance
Most AMR comes from the environment. It comes from: neglected ventilation systems, winds, waterways, soil, the dumping of pesticides and garbage, untreated dumping of waste from pharmaceutical industries, animal husbandry waste dumping, poorly treated municipal waters, untreated hospital waste, the food chain, the environment we live in, the animals we feed, the plants we depend upon to live, and the waste-water we generate.
The AMR Think-Do-Tank Geneva International is focused on advocacy, and action for mitigation, control, and monitoring of AMR in the Environment including Implementation Research (IR) on new or improved interventions, implementation strategies, policies, intersectoral dialogue, and engagement approaches. IR uses scientifically sound methodologies to produce real-life evidence for priority setting, public health action, and policy and regulation decisions.
The Think Tank is in the process of composing a multisectoral IR interest group whose first responsibility is to define an IR agenda for AMR and the Environment. This agenda will form the basis for competitively funded projects. A community of practice will provide support & mentorship to these projects. The projects will be embedded into national AMR programs, and capacity strengthening for research teams, implementers, and policymakers will be an integral part of the projects.
Final Panel discussion
This interactive session was led by Joakim Larsson along with a panel of experts namely; Sophie Gay, Will Gaze, Ed Topp, Sabiha Essack, Heike Schmitt, Christain Munthe, and Frank Aarestrup. Attendees participated using the menti website that followed a question-and-answer format. The questions, answers, and discussion points covered will be included in a report produced by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR), they included;
What are the knowledge gaps that relate to environmental dimensions of AMR and surveillance?
What are the "normal" levels of AMR in the environment
Standardizing the definition of surveillance
Surveillance for low resource settings
How other pollutants, excluding antibiotics, are affecting AMR
Why do we not have global AMR surveillance?
There is no proactive responsibility to do it, every agency tends to cover its segment: but now that the UNEP has joined the quadripartite, the infrastructure should be developed.
We need to understand what constitutes environmental surveillance, for example, monitoring wastewater influents may be considered an aspect of monitoring by certain agencies, which then conclude that they are carrying out environmental surveillance, but is it?
It is better to start with what we have but the microbiome is different in every region hence some target genes may function well in one area but not optimally in another.
We need to develop cheap and easily transferable surveillance methods.
2. What are the key knowledge gaps in environmental dimensions of AMR and transmission and evolution?
What are the important environments for AMR evolution
The scale at which AMR occurs
Our understanding of how antibiotic concentration affects the development of resistance may be overturned in the future because we are yet to understand how the synergies of different combinations of chemicals affect the evolution of AMR.
There is a need to develop robust models to predict trends, especially in cases where it is not possible/feasible to collect samples continuously.
3. Knowledge gaps that relate to environmental dimensions of AMR and therapeutics
An economic model to prevent drug discharge
Possibility of Phage therapeutics
We know little about the incentives that would motivate industries to improve their antibiotic production practices without having them choose to instead shift to other products.
Need for more resistant crops even if they are GMOs so that the need for fungicides is limited.
4. Knowledge gaps that relate to environmental dimensions of AMR and diagnostics
A faster way to screen for drug resistance
Possibility of diagnostics for AMR in crops
5. Knowledge gaps that relate to environmental dimensions of AMR and prevention and interventions
Methods for removing ARGs from wastewater
We need to improve the methods for implementation research because the solutions developed to work in high-income settings may not necessarily work in low-income settings.
EDAR 7, Montreal
The conference series will continue in 2024 and will be back in Canada, where it started. EDAR 7 will be held in Montreal, Canada, and hosted by McGill University. The conference will carry on with the one health agenda; break disciplinary silos and connect with public health, social sciences, and industry partners. It will cover the following issues;
Fundamental scientific aspects of the ecology and biology of AMR in the environment
Integration of wastewater and environmental surveillance
Experiences to mitigate environmental AMR
Translations of risk science into policy recommendations
Behavioural and economic dimensions of changing policy
AMR development in fungal, parasitic, and viral pathogens
Lessons learnt
Approaches for controlling antimicrobial resistance genes should work simultaneously with other pollutants' removal, such as COD - Chemical Oxygen Demand.
China stopped colistin use in animal feed in 2016 which reduced the prevalence of colistin resistance and has now banned the use of all animal feed antibiotics.
Antidepressants can enhance gene transfer in gut bacteria.
Socioeconomic factors are more influential in antimicrobial resistance development than antibiotic usage.
Wastewater treatment plant workers are safer than expected and not constantly exposed to antimicrobial resistance agents.
Even in good water quality conditions, people still ingest antimicrobial resistance genes during recreational activities and bathing.
Nomenclature needs to be addressed.
Many thanks to all the people attending this conference on site and online !
If you are interested in joining AMR TDT, our Think-Do-Tank is specifically looking for volunteers to help us with the communication efforts, and also experts in the following areas:
1. Healthcare environments – their contamination makes an important contribution to hospital-acquired multi-drug resistant infections.
2. Sewage - wastewater generated from domestic dwellings.
3. Wastewater Treatment Plants - Wastewater from non-residential and industrial sources
4. Airborne transmission.
please contact us !
Article by Natukunda Michelle
Edited & translated by Arno Germond
October 14, 2022