I have been slow at picking this ball up, but the book chapter that I coauthored with Stefanie Hess is now available online (and has been for almost a month). It is part of the book Antibiotic Drug Resistance, edited by José-Luis Capelo-Martínez and Gilberto Igrejas and was available in print on September 9th.
Our chapter deals with sources of resistant bacteria to the environment, and in particular the roles of sewage, wastewater and agriculture in resistance dissemination. Furthermore, the chapter discusses de novo selection of resistance and defines relevant risk scenarios. Finally, we outline the different management options available and discuss their feasibility.
The chapter boils down to that the available strategies for limiting antibiotic resistance dissemination and selection in the environment are overall quite clear. Larger problems that remain to be solved are how to prioritize between different strategies, which technologies that would provide the largest benefits and to achieve the political willingness to pursue these strategies. We note that several of the most efficient resistance prevention options involve high costs, investments in technology and infrastructure in other countries or proposals that are likely to be rather unpopular with the general public. For example, investing in sewage treatment and water infrastructure in low-income countries would likely be among the most effective means to reduce releases of resistant bacteria into the environment and reduced meat consumption would contribute to lower the use of antibiotics in animal husbandry, but neither is a very popular proposal for tax payers in high-income countries.
I have not yet read the entire book myself, but the table of content shows a very wide-reaching and comprehensive picture of the antibiotic resistance field, with a range of prominent authors. The editors have made a good job collecting this many interesting book chapters in the same volume!
Bengtsson-Palme J, Heß S: Strategies to reduce or eliminate resistant pathogens in the environment. In: Capelo Martinez JL, Igrejas G (Eds.) Antibiotic Drug Resistance, 637–673. Wiley, NJ, USA (2020). doi: 10.1002/9781119282549.ch24[Link]
I am happy to announce that Cancer- och Allergifonden [the Cancer and Allergy Foundation] have awarded me with the first Lennart Sparell prize. The prize was instated in memory of the foundations founder – Lennart Sparell, who passed away last year – and is awarded to researchers (or other persons) who have thought outside-of-the-box or challenged the current paradigms. A particular emphasis is given to research on environmental pollutants that affect human health through food or environmental exposure.
Naturally, I am honored to be the recipient of this prize. The award was motivated by the research I have done on the role of ecological and evolutionary processes in the external environment in driving antibiotic resistance development, and how that can have consequences for human health. Particularly, I am happy that the research that I, Joakim Larsson, Erik Kristiansson and a few others on the role of environmental processes in the development of antibiotic resistance and the recruitment of novel resistance genes are given attention. This view, which perhaps do not challenge the paradigm but at the very least points to an alternative risk scenario, has often been neglected when environmental antibiotic resistance has been discussed.
The prize will be awarded on a ceremony on June 10 in Stockholm, but I would already now take the opportunity to thank everyone who has been involved in the research being recognized, particularly Joakim Larsson and Erik Kristiansson – this award is to a very very large extent to your merit.
Time flies, and my first 2019 publication (wait what?) is now out! It’s a chapter in the book “Management of Emerging Public Health Issues and Risks: Multidisciplinary Approaches to the Changing Environment” (1), edited by Benoit Roig, Karine Weiss and Véronique Thireau. I have to confess to not having read the other chapters in the book yet, but I think the subject is exciting and hope for a lot of good reading over Christmas here!
My chapter deals with assessment and management of risks associated with antibiotic resistance in the environment (2), and particularly I make an attempt at clarifying the different types of risks and how to deal with them. In short, I partition resistance risks into two categories: dissemination risks and risks for acquisition of new types of resistance (see also 3). While the former category largely encompasses quantifiable risks, the latter is to a large extent impossible (or at least extremely hard) to quantify with current means. This means that we need to be a bit more creative in assessing, prioritizing and managing these risks. Some lessons can be learnt from other fields dealing with very uncertain (and rare) risks, such as asteroid impact assessment, nuclear energy accidents and ecosystem destabilization (4,5). Incorporating elements from such risk management schemes will be necessary to understand and delay emergence of novel resistance in the future.
All these aspects are further discussed in the book chapter (2), which I encourage everyone working with environmental antibiotic resistance risks to read!
- Roig B, Weiss K, Thoreau V (Eds.) Management of Emerging Public Health Issues and Risks: Multidisciplinary Approaches to the Changing Environment. Academic Press/Elsevier, UK (2019). doi: 10.1016/C2016-0-00995-6
- Bengtsson-Palme J: Assessment and management of risks associated with antibiotic resistance in the environment. In: Roig B, Weiss K, Thoreau V (Eds.) Management of Emerging Public Health Issues and Risks: Multidisciplinary Approaches to the Changing Environment, 243–263. Elsevier, UK (2019). doi: 10.1016/B978-0-12-813290-6.00010-X
- Bengtsson-Palme J, Kristiansson E, Larsson DGJ: Environmental factors influencing the development and spread of antibiotic resistance. FEMS Microbiology Reviews, 42, 1, 68–80 (2018). doi: 10.1093/femsre/fux053
- WBGU GACOGC: World in Transition: Strategies for Managing Global Environmental Risks. Springer
Berlin Heidelberg, Berlin, Heidelberg (2000).
- Government Office for Science: Blackett Review of High Impact Low Probability Events. Department for
Business, Innovation and Skills, London (2011).
Recently, Le Page et al. published a paper in Environmental International (1), partially building on the predicted no-effect concentrations for resistance selection for 111 antibiotics that me and Joakim Larsson published around two years ago (2). In their paper, the authors stress that discharge limits for antibiotics need to consider their potency to affect both environmental and human health, which we believe is a very reasonable standpoint, and to which we agree. However, we do not agree on the authors’ claim that cyanobacteria would often be more sensitive to antibiotics than the most sensitive human-associated bacteria (1). Importantly, we also think that it is a bit unclear from the paper which protection goals are considered. Are the authors mainly concerned with protecting microbial diversity in ecosystems, protecting ecosystem functions and services, or protecting from risks for resistance selection? This is important because it influence why one would want to mitigate, and therefore who would perform which actions. To elaborate a little on our standpoints, we wrote a short correspondence piece to Environment International, which is now published (3). (It has been online for a few days, but without a few last-minute changes we did to the proof, and hence I’m only posting about it now when the final version is online.) There is indeed an urgent need for discharge limits for antibiotics, particularly for industrial sources (4) and such limits would have tremendous value in regulation efforts, and in development of environmental criteria within public procurement and generic exchange programs (5). Importantly, while we are all for taking ecotoxicological data into account when doing risk assessment, we think that there should be solid scientific ground for mitigations and that regulations need to consider the benefits versus the costs, which is what we want to convey in our response to Le Page et al.
- Le Page G, Gunnarsson L, Snape J, Tyler CR: Integrating human and environmental health in antibiotic risk assessment: a critical analysis of protection goals, species sensitivity and antimicrobial resistance. Environment International, in press (2017). doi: 10.1016/j.envint.2017.09.013
- Bengtsson-Palme J, Larsson DGJ: Concentrations of antibiotics predicted to select for resistant bacteria: Proposed limits for environmental regulation. Environment International, 86, 140–149 (2016). doi: 10.1016/j.envint.2015.10.015
- Bengtsson-Palme J, Larsson DGJ: Protection goals must guide risk assessment for antibiotics. Environment International, in press (2017). doi: 10.1016/j.envint.2017.10.019
- Bengtsson-Palme J, Larsson DGJ: Time to limit antibiotic pollution. The Medicine Maker, 0416, 302, 17–18 (2016). [Paper link]
- Bengtsson-Palme J, Gunnarsson L, Larsson DGJ: Can branding and price of pharmaceuticals guide informed choices towards improved pollution control during manufacturing? Journal of Cleaner Production, 171, 137–146 (2018). doi: 10.1016/j.jclepro.2017.09.247
In two weeks time, on the 15th of June, I will participate in a seminar organised by Landstingens nätverk för läkemedel och miljö (the Swedish county council network for pharmaceuticals and environment; the seminar will be held in Swedish) in Stockholm. I will give a talk on our proposed emission limits for antibiotics published last year (the paper is available here), but there will also be talks on wastewater treatment, sustainable pharmaceutical usage and environmental standards for pharmaceuticals. The full program can be found here, and you may register here until June 9. The seminar is free of charge.
And if you are interested in this, I can also recommend the webinar given by Healthcare Without Harm next week (on June 8), which will deal with sustainable procurement as a means to deal with pharmaceutical pollution in the environment. I will at least tune in to hear how the discussion goes here.
First of all, I am happy to announce that the webinar I participated in on the (un)recognised pathways of AMR: Air pollution and food, organised by Healthcare Without Harm is now put online so that you can view it, in case you missed out on this event. To be honest it is probably not one of my best public appearances, but the topic is highly interesting.
Second, next week I am taking part in Vetenskapsfestivalen – the Science Festival in Gothenburg. Specifically, I will be on of the researchers participating in the Science Roulette, taking place in the big ferris wheel at Liseberg. This will take place between 17.00 and 18.00 on May 11th. The idea is that people will be paired with researchers in diverse subjects, of which I am one, and then have a 20 minute chat while the wheel is spinning. Sounds like potential for lot of fun, and I hope to see you there! I will discuss antibiotic resistance, and for how much longer we can trust that our antibiotics will work.
Sorry for the late notice, but if you have half an hour to spare later today I will discuss our findings on resistance genes in Beijing air on a webinar organised by Healthcare Without Harm on “The (un)recognised pathways of AMR: Air pollution and food“. Tune in a few minutes before 16.00 CEST!
After the usual (1,2) long wait between acceptance and publication, Science of the Total Environment today put a paper online in which I have played a role in the bioinformatic analysis. In the paper, we investigate whether antifouling paint containing copper and zinc could co-select for antibiotic resistance, using microbiological methods and metagenomic sequencing (3).
In this work, we have studied marine microbial biofilms allowed to grow on surfaces painted with antifouling paint submerged in sea water. Such antifouling paints often contain metals that potentially could co-select for antibiotic resistance (4). Using microbiological culturing, we found that the heavy-metal based paint co-selected for bacteria resistant to tetracycline. However, the paint did not enrich neither the total abundance of known mobile antibiotic resistance genes nor the abundance of tetracycline resistance genes in the biofilm communities. Rather, the communities from the painted surfaces were enriched for bacteria with genetic profiles suggesting increased capacity for extrusion of antibiotics via RND efflux systems. In addition, these communities were also enriched for genes involved in mobilization of DNA, such as ISCR transposases and integrases. Finally, the biofilm communities from painted surfaces displayed lower taxonomic diversity and were at the same time enriched for Gammaproteobacteria. The paper builds on our previous work in which we identify certain co-occurences between genes conferring metal and antibiotic resistance (4). However, the findings of this paper do not lend support for that mobile resistance genes are co-selected for by copper and zinc in the marine environment – rather the increase in antibiotic resistance seem to be due to taxonomic changes and cross-resistance mechanisms. The entire paper can be read here.
- Bengtsson-Palme J: Published paper: Community MSCs for tetracycline. https://microbiology.se/2016/03/22/published-paper-community-mscs-for-tetracycline/
- Bengtsson-Palme J: Published paper: Antibiotic resistance in sewage treatment plants . https://microbiology.se/2016/08/17/published-paper-antibiotic-resistance-in-sewage-treatment-plants/
- Flach C-F, Pal C, Svensson CJ, Kristiansson E, Östman M, Bengtsson-Palme J, Tysklind M, Larsson DGJ: Does antifouling paint select for antibiotic resistance? Science of the Total Environment, in press (2017). doi: 10.1016/j.scitotenv.2017.01.213 [Paper link]
- Pal C, Bengtsson-Palme J, Kristiansson E, Larsson DGJ: Co-occurrence of resistance genes to antibiotics, biocides and metals reveals novel insights into their co-selection potential. BMC Genomics, 16, 964 (2015). doi: 10.1186/s12864-015-2153-5 [Paper link]
I will give a short talk on our findings related to antibiotic resistance associated with pharmaceutical production facilities in India at a one-hour webinar arranged by Healthcare Without Harm, taking place on Thursday, November 3rd, 10.00 CET. The webinar will discuss “hot-spot” environments in which antimicrobial resistance can emerge, such as areas in which there are poor pharmaceutical manufacturing practices, where expired or unused drugs are disposed of in an inappropriate way (i.e. by flushing them down the toilet or sink, or disposing them in household rubbish), and areas in which pharmaceuticals are used for aquaculture or agriculture. This is an important aspect of the resistance problem, but to date most of the actions taken to tackle the spread of AMR don’t take into account this aspect of antimicrobials released into the environment. The webinar is co-organised by HCWH Europe and HCWH Asia, and aims to raise awareness about the issue of AMR and its environmental impact. It features, apart from myself, Lucas Wiarda (Global Marketing Director & Head of Sustainable Antibiotics Program at DSM Sinochem Pharmaceuticals) and Sister Mercilyn Jabel (Pharmacist at Saint Paul Hospital Cavite, Philippines).
Sign up here to learn about:
- Antibiotic pollution and waste
- Recent findings from India regarding antibiotic discharges in rivers from manufacturers and new mechanisms by which resistance spreads in the environment
- Sustainable antibiotics – how to support the proper and effective use of antibiotics and their responsible production
- How the pharmaceutical industry is addressing the environmental pollution that leads to AMR
- The best practices in managing infectious waste at hospital level
Me and Joakim Larsson wrote an opinion/summary piece for the APUA Newsletter, issued by the Alliance for Prudent Use of Antibiotics, that was published yesterday (1). The paper is essentially a summary of work included in my PhD thesis, and discusses how to establish minimal selective concentrations of antibiotics for microbial communities (2-4), how to identify risk environments for resistance selection (5-9), and which mitigation strategies that can be implemented (10-12). Partially, we also discussed these issues earlier in our paper in the Medicine Maker (10), but this paper goes deeper into why limiting antibiotic pollution is important to mitigate the accelerating antibiotic resistance problem. I recommend this short summary piece to anyone who would like a brief overview of our research on antibiotic resistance, and think that it can serve as a great starting point for further reading! In addition, this issue of the newsletter features very interesting pieces on reducing antibiotics use (and disposal) outside of the clinics (13) and revival of old antibiotics (14). Please go ahead to the APUA web site and read the entire newsletter!
- Bengtsson-Palme J, Larsson DGJ: Why limit antibiotic pollution? The role of environmental selection in antibiotic resistance development. APUA Newsletter, 34, 2, 6-9 (2016). [Paper link].
- Bengtsson-Palme J, Larsson DGJ: Concentrations of antibiotics predicted to select for resistant bacteria: Proposed limits for environmental regulation. Environment International, 86, 140-149 (2016). doi: 10.1016/j.envint.2015.10.015 [Paper link]
- Gullberg E, Cao S, Berg OG, Ilbäck C, Sandegren L, Hughes D, et al.: Selection of resistant bacteria at very low antibiotic concentrations. PLoS Pathogens 7, e1002158 (2011).
- Lundström S, Östman M, Bengtsson-Palme J, Rutgersson C, Thoudal M, Sircar T, Blanck H, Eriksson KM, Tysklind M, Flach C-F, Larsson DGJ: Minimal selective concentrations of tetracycline in complex aquatic bacterial biofilms. Science of the Total Environment, 553, 587–595 (2016). doi: 10.1016/j.scitotenv.2016.02.103
- Bengtsson-Palme J, Boulund F, Fick J, Kristiansson E, Larsson DGJ: Shotgun metagenomics reveals a wide array of antibiotic resistance genes and mobile elements in a polluted lake in India. Frontiers in Microbiology, 5, 648 (2014). doi: 10.3389/fmicb.2014.00648
- Bengtsson-Palme J, Hammarén R, Pal C, Östman M, Björlenius B, Flach C-F, Kristiansson E, Fick J, Tysklind M, Larsson DGJ: Elucidating selection processes for antibiotic resistance in sewage treatment plants using metagenomics. Science of the Total Environment, in press (2016). doi: 10.1016/j.scitotenv.2016.06.228
- Berendonk TU, Manaia CM, Merlin C, Fatta-Kassinos D, Cytryn E, Walsh F, et al.: Tackling antibiotic resistance: the environmental framework. Nature Reviews Microbiology, 13, 310–317 (2015). doi: 10.1038/nrmicro3439
- Martinez JL, Coque TM, Baquero F: What is a resistance gene? Ranking risk in resistomes. Nature Reviews Microbiology 2015, 13:116–123. doi:10.1038/nrmicro3399
- Bengtsson-Palme J, Larsson DGJ: Antibiotic resistance genes in the environment: prioritizing risks. Nature Reviews Microbiology, 13, 369 (2015) doi:10.1038/nrmicro3399‐c1
- Bengtsson-Palme J, Larsson DGJ: Time to limit antibiotic pollution. The Medicine Maker, 0416, 302, 17–18 (2016). [Paper link]
- Ashbolt NJ, Amézquita A, Backhaus T, Borriello P, Brandt KK, Collignon P, et al.: Human Health Risk Assessment (HHRA) for Environmental Development and Transfer of Antibiotic Resistance. Environmental Health Perspectives, 121, 993–1001 (2013)
- Pruden A, Larsson DGJ, Amézquita A, Collignon P, Brandt KK, Graham DW, et al.: Management options for reducing the release of antibiotics and antibiotic resistance genes to the environment. Environmental Health Perspectives, 121, 878–85 (2013).
- Theuretzbacher U: Optimizing the Use of Old Antibiotics — A Global Health Agenda. APUA Newsletter, 34, 2, 10-13 (2016). [Paper link].
- Amábile-Cuevas CF: Antibiotics and Antibiotic Resistance All Around Us. APUA Newsletter, 34, 2, 3-5 (2016). [Paper link].