Understanding antimicrobial resistance will advance reduction efforts

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Proper understanding of antimicrobial resistance crucial to advancing industry’s reduction efforts

Since Sweden banned antimicrobial growth promotors in 1986, many countries have continued to restrict the widespread application of antimicrobials, thereby reducing the main driver of antimicrobial resistance (AMR).

In fact, according to Dr. Nataliya Roth, DSM Animal Nutrition & Health’s Global Portfolio Lead for Microbiome Modulation, the successful reduction of antimicrobial consumption and AMR can clearly be seen in national and international monitoring statistics. “Total antimicrobial sales decreased by 38% from 2015 to 2020 in the US and a decline of 43.2% in sales was reported in 25 European countries between 2011 and 2020,” she explained to Feedinfo during an Industry Perspectives chat. “The reduction in antimicrobial use leads to lower prevalence of antimicrobial resistance, which is clearly shown in the monitoring reports.”

However, she added, calls by consumers, regulators and health bodies suggest that there is more work to be done.

Here Dr. Roth dives a little deeper into what exactly this work might entail and shares how DSM, as part of its We Make It Possible sustainability initiative, is helping to advance AMR efforts in animal agriculture. [Feedinfo] Dr. Roth, in your opinion, what AMR approaches have worked and what approaches do you believe need to be re-evaluated? [Nataliya Roth] It’s not simply about decreasing antimicrobial use alone, which can have unwanted consequences on animal health, welfare and productivity. A holistic One Health strategy that uses a full set of tools including nutrition, feed additives and production management has proven most promising to ensure animal productivity, health and sustainability.

I do not see the need for re-evaluation of this approach, but rather the need for global harmonisation of standards and monitoring. Many countries and regions have established or are in the process of establishing monitoring of antimicrobial use and resistance for animals. It would be very reasonable to use the same harmonised methodologies to detect antimicrobial resistance and use of antimicrobials per animal species. Additionally, the classification of antimicrobials sometimes differs. For example, ionophores are considered antibiotics in the US but as feed additives in the EU.

While reduction of antimicrobial use can be further improved, there is another strategy that deserves more attention: focus on the transmission of antimicrobial resistance. One challenge is that AMR genes and AMR bacteria can be exchanged between other bacteria, animals, humans and the environment. Cutting that connection through improved sanitation, infection control and prevention could help us to make further progress against antimicrobial resistance. [Feedinfo] So, in terms of helping the industry cut that connection, where is DSM placing its focus? [Nataliya Roth] Working with the public, global and national authorities, research organisations and AMR network groups cooperating with WHO, FAO and OIE, DSM has put advanced scientific knowledge to work for the benefit of our customers. We offer services for detection of AMR and health issues as well as innovative products.

Regulatory restrictions on the use of On the detection side, we are antimicrobials globally. advocating for two distinct technological applications. The first involves using

Year Ban Countries novel methodologies to evaluate the 2006 All AGPs EU gut microbiome, the total population 2007 Most AGPs Mexico of antimicrobial resistant genes 2017 Colistin China (the resistome) and gut health biomarkers. The second uses blood 2017 AGPs USA testing, biomarker analysis and 2020 All AGPs China machine learning to identify disease Modified after Feiyang et al, 2021 outbreaks before they occur, providing valuable insight to customers who can take preventive action and avoid the need for application of antimicrobials. Our products include tailored premix solutions and one of the industry’s best-in-class portfolio of innovative additives that promote gut health and efficiency. Because health and nutrition are inextricably linked, we think there’s incredible value for our clients in having the full picture and all the necessary tools to improve their operations. [Feedinfo] Now, as you’ve explained, antibiotic use has fallen in animal nutrition globally. But what is the case with critically important therapies? [Nataliya Roth] Critically important antibiotics are crucial for use in human medicine. In many countries, special restrictions for highest priority, critically important antimicrobials have been implemented or are planned. Restrictions on the use of medically important antimicrobials in the US nearly 20 years ago was an important achievement. The results can be observed in the very low prevalence of resistance

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to fluroquinolones in comparison to other countries. In Europe the sales of polymyxins and quinolones in the EU between 2015 and 2020 were reduced by 70% and 74%, respectively. Since January 2022, new European legislation bans the use of antimicrobials reserved for human medicine for routine antibiotic use in farming, including preventative group treatments of animals before clinical signs of disease. The use of colistin has been banned in China since 2017 for both growth promotion and treatment of animals.

[Feedinfo] How does the reduction of antibiotic use impact the prevalence of antibiotic resistant pathogens? What is important for the industry to understand here?

“While reduction of antimicrobial use can be further improved, there is another strategy that deserves more attention: focus on the transmission of antimicrobial resistance.”

NATALIYA ROTH

[Nataliya Roth] Properly understanding the AMR problem provides a clear direction. Antimicrobial resistance is a natural phenomenon that dates back millions of years as an instrument for competition among microorganisms. Bacteria are able to develop mechanisms to protect themselves. The reason why AMR has the potential to become a silent pandemic is that antimicrobial use in high quantities in many areas including human and animal medicine puts added pressure on this evolutionary trait — steering microbial populations towards greater resistance.

Data on antimicrobial use and resistance in human and animal health in Europe and in the US provides evidence that bacterial populations are not interested in keeping the AMR genes in the absence of selective pressure applied by antibiotic use. The important, positive message to the industry is that antimicrobial resistance is reversible. The reduction of antimicrobial use leads to the reduced prevalence of antimicrobial resistant microorganisms and genes. It is also clear that antimicrobials should not be replaced by other antimicrobials and the use of other AMRtriggering biocides should be restricted. The target is the reduction of AMR, because complete and total elimination of AMR will never be possible. Getting AMR levels down is key to ensuring that our medicines are effective when we need them.

[Feedinfo] What are the proven feed additive solutions that can have an impact on the prevalence and transmissibility of antibiotic resistant bugs? And how effective are they?

[Nataliya Roth] It is known that some feed additives like acids, phytogenics, probiotics and prebiotics, are able to reduce and to modify the bacterial load in the gastrointestinal tract of animals. We have evaluated the efficacy of several molecules and solutions on the prevalence of AMR bacteria and genes in the gut of animals. The reduction was confirmed by means of many scientific trials as well as large field trials.

It was extremely interesting to observe that some molecules have the potential to significantly reduce the prevalence of so-called superbug Extended Spectrum Beta-Lactamase- (ESBL-) producing E. coli in the gut significantly in comparison to the control groups. The use of 3rd and 4th generation of cephalosporins that leads to the development of ESBL-producing microorganisms is strictly regulated to prevent the formation of ESBL producers. The possibility to reduce the prevalence of ESBLs in the gut will surely be more important in the future.

[Feedinfo] Talking about the future, what are the technologies or solutions to potentially help the industry meet its AMR ambitions which DSM is most excited about? What do you have in the pipeline?

[Nataliya Roth] The development of new sequencing technologies to detect AMR in recent years is impressive. Strong internal research enables us to use the newest available technologies combined with machine learning to collect high quality data to understand AMR dynamics. The use is possible not only for research purposes but also on farms in different countries supporting animal producers to identify the problem, reduce antimicrobial use and resistance and reduce the transmission of AMR to other ecosystems.

We offer services that can predict certain diseases or evaluate microbiome, pathobiome and resistome in the animal’s gut which supports animal producers globally in preventing disease outbreaks, reducing both antimicrobial use and antimicrobial resistance. Looking ahead, we see the potential to expand the adoption of these tools and introduce further developments in the gut health space, including enzymes and microbiome modulation technology, within our holistic species solutions designed to add value for our customers.