Biopollution: Antimicrobial resistance in the environment

Meeting report by Roger Reeve
ECG Committee Member
rgrreeve@gmail.com
ECG Bulletin July 2018

Joackim larsson

andrew singer

celia manaia

The topic for the 2018 Distinguished Guest Lecture and Symposium, held on March 28 2018, was the global problem of developing resistance to drugs and the importance of understanding the role that the environment plays in its control. Much of the popular media publicity has been centred on the over-use of antibiotics for medical prescriptions, but resolving the problem will be more complex.

Antimicrobial compounds can enter the water supply from hospitals and from domestic use via sewage treatment plants, and antimicrobial resistant organisms can therefore build up in the environment. From here, antibiotic-resistant genes can be transferred through the ecosystem and ultimately back to human pathogens with severe implications for healthcare. Of particular concern is the major use of antibiotics in the farming industry, often with similar compounds to those used in human healthcare. And, finally, the environment itself contains reservoirs of antibiotic resistant genes which also could be transmitted back to affect human healthcare.

The morning session was convened by Dr Zoë Fleming, chair of the ECG. The first presentation was by Dr Andrew Singer (Natural Environmental Research, Centre for Ecology and Hydrology) and gave ‘An Environmental Chemist’s Introduction to the Global Crisis of Antibiotic Resistance’. After an introduction to the different types of antimicrobials (chemicals that kill or inhibit viruses, bacteria, fungi, protists and worms), the talk concentrated on the specific problems of antibiotics. Different classes of antibiotics were introduced as well as the four main mechanisms by which resistance occurs. In the west, antibiotics from human use largely enter the environment through waste water treatment plants. Farming is an additional input into the environment.  A gap in current knowledge is the relative contribution of waste water treatment plants and farm run-off to antimicrobial resistance. In order to bridge this gap, Dr Singer’s group researches aquatic reservoirs of antibiotic resistant bacteria at the catchment scale. Monitoring around some sewage work outfalls has shown hotspots of resistance. Modelling is used to predict resistance build up, based on the antibiotic usage within the catchment and the impact of future reductions in usage. The importance of co-selectives, including metals and biocides, in resistance pathways is becoming apparent. Reductions in all uses of antimicrobials may be required to achieve sustainable reduction of drug-resistant infections in humans.

Professor Célia Manaia (Universidade Catolica Portuguesa) followed with a talk entitled ‘Antibiotic Resistance — from Nature to Environmental Contaminants’. Antibiotic resistance in the environment can be natural as well as anthropogenic. Entry to the environment following human use can occur via hospital effluent or waste water treatment plants. Waste water treatment plants are important resistance reservoirs in the urban environment. Improving waste water treatment needs to establish a compromise between chemical and biological control. Any disinfection such as ozonation or UV treatment must not be too aggressive towards the treatment plant microbiota. There is also an additional input to the environment from farm use of antibiotics. Mitigations suggested are the identification of critical control points and action at these points. Continual surveillance on an international scale is also necessary, and three current projects were mentioned. A question was asked concerning possible modification of sewage treatment plants. All options are expensive, so a cost benefit analysis is necessary during the selection. There are also some locations in the world where the agricultural input may be more important to control.

After a short break, the meeting continued chaired by the Distinguished Guest Lecture organiser, Dr Rowena Fletcher-Wood. Dr Lee Slater (Dept of the Environment, Food and Rural affairs) continued with ‘Anthropogenic Source Antimicrobial Resistance in the Environment— Implications to Policy and Environmental Management Practice’. By its nature, policy formulation takes many years. Development is within a continuous cycle—definition of issue, understanding the problem, control options, engagement with stakeholders, evidence and analysis, returning to a redefinition. Control of antimicrobial resistance is at the first ‘understanding the problem’ stage. Care has to be taken that a decision is not made to promote one direction that, with hindsight, proves to not be the most important action. This does not mean that there should be complacency – several examples were given of compounds which had unexpected consequences. The precautionary principle should be borne in mind, but this should only be on the basis of firm scientific principles. We can all help to formulate policy, as individuals, as leaders or future leaders, or as educators or as an industry. One delegate questioned the timescale involved in comparison with the proven need for action— no new antibiotics are in the pipeline and the lifetime of antibiotics before resistance is developed is only a few years. The response was encouraging that, although policy may take many years, it was an evolutionary process and interim guidance could be produced as evidence grows.

The Distinguished Guest Lecturer was Professor Joackim Larsson (University of Gothenburg). He is currently the Director of the Centre of Antibiotic Resistance involving more than 100 researchers from six faculties. The presentation started by giving the reasons to consider the importance of the environment in antibiotic resistance. Understanding environmental antibiotic resistance gives a possible indication of regional clinical resistance, defines transmission routes for resistant bacteria (human/animal to environment to human/animal) and could also have importance as an evolutionary arena for the emergence of new forms of resistance (favoured by a selection pressure from presence of antibiotics). There is evidence developing from studies in European counties showing a correlation between E. coli resistance in untreated sewage to resistance in clinical blood stream infections. Antibiotic resistance in the environment is ancient. Conditions to promote resistance build-up can happen anywhere and at any time. This may occur in the gut, but evidence is building that this also occurs in the environment due to background low concentrations of antibiotics.

Entry of waste water in the environment in the west is usually via sewage treatment plants. Determining the relative contribution of antibiotic concentrations and transfer of resistance is difficult as they have a common source. The overall effect of the treatment plants is complex and dependent on plant design and operation. One study of a plant with and without ozonation tertiary treatment showed that ozonation reduced antibiotics in effluents and downstream sediment to non-detectable levels, but the presence of resistant genes in downstream sediment was not affected.

Another inputs of antibiotics into the environment includes farming. In locations such as India or China, discharge from antibiotic production plants is important. High concentrations are found in surface, ground and drinking water and wildlife. India has produced a national action plan which includes setting antibiotic discharge limits from industry, farms, healthcare and veterinary care but is the only country so far to do so. This is also a recommendation in the recent O’Neil UK report.

Figure 1. Professor Joakim Larsson with his 2018 Distinguished Guest Lecture medal presented by Dr Rowena Fletcher-Wood. Photographed at the Royal Society of Chemistry Centre, Burlington House

A question followed defining the resistance issue – which area is of most concern within this highly complex problem? The most important areas may differ in different geographical locations. In the west, municipal waste treatment may be the most important, whereas in the east, more diverse environmental considerations may take priority.

The meeting concluded with the presentation of the 2018 Distinguished Guest Lecture medal to Professor Larsson.

The delegates left the meeting appreciating both the complexity of the problems and also the research currently underway to define areas of greatest importance as a step-forward to control of resistance.