The reservoir of resistance genes in waterways is increasing

Sample collection downstream from a waste water treatment plant | © Karin Beck, Eawag

Waterways play a key role in the spread of antibiotic resistance in and through the environment. From 16 to 19 September, over 40 international scientists met in Ascona to discuss measures to mitigate resistance in this area.

In an interview, Helmut Bürgmann, chief organiser of the HEARD (Halting Antimicrobial Resistance Dissemination in Aquatic Environments) conference and NRP 72 researcher, reflects optimistically about specific approaches to solutions that science will be able to deliver relatively quickly – provided the political will is there.

At the HEARD conference, you and your colleagues from all over the world conferred for four days about the current state of knowledge of antimicrobial resistance in water systems. Where do we stand with respect to measures for fighting resistance?

Our research field is very young, but in recent years it has made great progress. In particular, methods are developing rapidly, which in turn makes a variety of applications possible.

Could you give me one specific example?

Researchers have detected antibiotic-resistant Escherichia coli bacteria and a large variety of resistance genes in general in samples from toilets and sewage works at a German airport. Thanks to rapid genetic analyses, it is now possible to routinely monitor and promptly detect cases of resistant pathogens spreading internationally through airport sewage systems.

Is that easy to do?

For such a system to function across borders, we first need a standard international definition of what exactly it is we are looking for. We also need to know the precise markers that signal clinically relevant resistance. Indeed, the current discussion keeps coming back to the definition of reliable threshold values, i.e. the question of when resistance is critical. At the HEARD conference we were presented with many good examples from studies that use very powerful methods and produce lots of information. But whether generally applicable tools will emerge from this remains to be seen. In any case, it is also very important to develop simple test procedures that can easily be applied by practitioners in cantonal laboratories, for example.

This issue of simplified methods was a big topic in small group discussions at the HEARD conference.

Close interactions are very important in this field, because you’re looking at the practical aspects of a range of methods. And sometimes you happen to come upon unexpected solutions that you won’t find in any scientific journal, but which can be decisive for the problem you’re working on. That’s the advantage and the charm of a small conference like ours: the participants have enough time for personal discussions. By the way, that was also true between leading research figures and younger scientists, who accounted for around a third of the participants.

Especially in human medicine, many new and simple testing tools are currently being developed for rapid detection of resistance. Do these tools also benefit environmental research?

In the environment we are dealing with a much greater variety of microorganisms than in human medicine. Clinical approaches therefore require considerable adaptation to be useful to us. It becomes even more difficult if we want to go beyond mere monitoring and clarify fundamental questions, such as which types of transport are responsible for spreading resistance in the environment, or how antibiotic combinations affect an ecosystem. Here we benefit from the fact that gene analysis in general has made enormous progress and that today we can identify all the resistance genes in a sample or even an ecosystem in a very short amount of time.

Why is that important?

Because resistance is not only spread by pathogens but also by other bacteria. So we need a broader picture of resistant bacteria in order to understand the development and spread of resistance in the environment.

Another aspect, which you are also investigating in the context of NRP 72, is how to assess the risks arising from resistance in waterways. Where does that research now stand?

You have to differentiate: we divide the risk analysis roughly into two categories, which differ primarily in their complexity and communicability. We already have a good basis for determining immediate risks, such as the risk of becoming infected with resistant bacteria while swimming. The spread of pathogens in water and the associated risk of infection are a consequence of the amount of pollution. With appropriate backing from lawmakers at the national, European and even global level, suitable methods and limit values could be determined within a reasonable period of time.

Once you have identified specific risks, how do you reduce them?

If the levels are too high downstream of wastewater treatment plants, temporary bans on swimming could be imposed. Another alternative is disinfection processes, for example in systems in which ozonation has already been put in place for the removal of micropollutants. In India and South-East Asia, which have far greater problems in this area, risks could be reduced efficiently and relatively cheaply by introducing sanitary facilities.

You mentioned other groups of risks.

Right. I was referring to long-term risks, which are difficult to measure and hard to understand. The reservoir of resistance genes in waterways and the environment in general is constantly increasing through the introduction of ever greater amounts of faecal bacteria, antibiotic residues, disinfectants, pharmaceutical waste and so on. Future pathogens can exploit this reservoir. The rather random process by which a pathogen acquires new resistance becomes more probable because the number of transfers between resistance genes increases. We are dealing with an ever growing “bow wave” that could inundate us.

Yet you can’t estimate the precise risks?

They can only be roughly estimated. We will probably never be able to develop tools that are 100% accurate. And naturally that makes it even harder to communicate the specific risks related to these already complex processes.

Are there any specific actions that can be taken vis-à-vis this resistance reservoir in order to prevent the development of new antibiotic resistance?

As far as the most important measures are concerned, the situation in Switzerland and Europe is relatively good at the moment. A whole package of measures has already gone into effect or is being implemented, ranging from regulating the use of antibiotics in humans and animals to wastewater treatment to proper hygiene for food and drinking water. On the other hand, anecdotal evidence from other parts of the world, such as South-East Asia, shows that poor sanitation, combined with high population density, a different approach to animals and much more frequent use of antibiotics, greatly increases the risks. So there is substantial scope for intervention there. Generally speaking, it’s always a question of reinforcing barriers along the likely route of spread. That applies to both the infection risk and the reservoir risk.

However, the impact of any single measure on the resistance reservoir is much less clear than for infection risks.

Where do you still see gaps in knowledge?

We understand relatively well how resistance genes from humans or animals get into the environment. Less clear is the link in the other direction. How do resistance genes from the environment get into the intestinal flora? And can they become established there over the longer term? The chain of effects between waterways, groundwater, soil and food is long, and causal only to a limited extent. However, we know that everything is connected: one health, one water, one world.

• Website HEARD *HEARD (Halting Environmental Antimicrobial Resistance Dissemination) is an international collaborative of 14 partner institutions focused on quantifying the role that wastewater treatment plays in global dissemination of antimicrobial resistance
• NRP 72 project "Antibiotic Resistance from Waste Water Treatment Facilities in Swiss Streams and Rivers” (the project is part of the HEARD collaborative).
• Current publications