In an interview with ChileCarne, Lorenzo Fraile, Doctor of Veterinary Medicine in the field of Experimental and Clinical Pharmacology from the School of Veterinary Medicine of Zaragoza, and Associate Professor at the University of Lleida, talks about the importance of antimicrobial resistance, new European legislation, future regulatory changes and restrictions on the use of veterinary drugs, and the best strategy to control antimicrobial resistance in practice.

1. How would you define antimicrobial resistance and why is it important?

Antimicrobial resistance is a natural defense mechanism of bacteria against antibiotics. Bacteria are living beings and they try to find ways to survive. Thus, one survival mechanism of these microorganisms is based on becoming resistant to antibiotic substances. This strategy is ancient; it was already present when life began. It wasn’t developed after we created antibiotics; it precedes the human use of these drugs. For example, resistance mechanisms have been described in bacteria since the age of mammoths. We select bacteria with resistance mechanisms due to their exposure to antibiotics, increasing the population that has these resistance genes. In short, what we try to do by using antibiotics prudently is preserve, for as long as we can, the largest number of available antibiotics by using them in the best possible way. We need to understand that antimicrobial resistance is inevitable because it is natural. What we should do instead is reduce its proliferation and expansion due to the use of antibiotics.

When trying to stop a bacterial infection in an animal or a person, you don’t know if the bacteria have resistance genes. If certain antibiotics have been used for many years, it’s normal to find people or animals with bacteria that carry these resistance genes. This can certainly make treatment difficult. Preventing a high presence of antimicrobial resistance in bacterial populations ensures that we can use antibiotics properly in people and animals, and for a longer amount of time.

2. Which veterinary drugs does the European legislation focus on and why?

The new European legislation on veterinary drugs, which will enter into force in 2022, focuses on antibiotics for bacterial infections because they are considered critical for the future. It also talks about other antimicrobials to treat protozoa and viruses (antivirals), but to a lesser degree. This is due to the relevance of the “One Health” approach, meaning that efforts must be made to reduce antimicrobial resistance on all fronts. On the one hand, reducing this problem among humans, based on the better use of antibiotics by physicians. On the other hand, a veterinary approach, with better use of antibiotics on farm animals, dogs and cats, as well as other companion animals that come into direct contact with people. Another factor to consider is the environment, because we are part of the world and we are in contact with elements such as water, where these resistance genes are present in bacteria. That’s why the legislation focuses on antibiotics and this idea of One Health, which includes the use of antibiotics in people, animals, and their dissemination in the environment. We have been fighting this for years now, while veterinarians and physicians were pointing fingers at each other. Now we know that everyone has their share of responsibility and we all need to work on it in our respective fields.

Legislation increasingly incorporates the concept of One Health and antibiotics is the group of drugs on which legislative pressure is focused because there are fewer resistance issues with the rest of antimicrobials. Antibiotics have been heavily studied by those who promote One Health and they have become a public health issue. Today, what each producer does on their farm impacts this One Health concept. If antibiotics are properly used in livestock farming, there will be a global positive impact (veterinary, human, and environmental).

The Spanish pork sector wants to keep producing meat, keep exporting, and it wants to make a living from it. Therefore, the pork sector is doing its part to minimize antimicrobial resistance. That is the general idea in Spain and I hope that in the future we will all be on the same page.

3. Are all veterinary antibiotics equally likely to produce resistance?

No, they are not. Looking at the resistance of a drug family, not all of them have the same probability of producing antimicrobial resistance. There are families that produce resistance more easily. For example, quinolones are more likely to produce resistance through various mechanisms. Legislation in Europe contemplates antibiotics divided into four categories: A, B, C, and D.

Going forward, those that are safest for humans are category D. Category C can be used when there are no other alternatives or those in category D are not clinically effective. If neither D nor C work in a clinical case, category B drugs can be used. Category B contains the drugs that are more likely to produce resistance in animals and have a higher potential impact on people. This group includes quinolones, cephalosporins, and polymyxins. Finally, there is category A, drugs that are not authorized for use in food-producing animals. They are restricted for use in humans and are also last-resort antibiotics of exceptional use.

4. In your opinion, what regulatory changes or restrictions on the use of antimicrobials will be implemented in the future?

I hope that if we comply with the new European legislation we have committed to and optimize the use of these molecules, I do not believe that more restrictive regulations will be needed. We have reached a point where I think it would be difficult to do so; otherwise, the next step would be banning certain drugs and/or entire antibiotic families, which could compromise animal welfare. Some European countries are putting a lot of pressure on this field, especially the Nordic countries, because it has always been their cause.

5. In your opinion and experience, what is the best strategy to control antimicrobial resistance and ensure a responsible and prudent use of antimicrobials?

The solution to this issue is multifactorial. For example, if all antibiotics are banned, consumption and resistance obviously decrease, but this has been studied and it is not directly related. It does not occur in all families. There is a causal relationship, but it is not direct. Consequently, it’s clear that a ‘large-scale’ ban is not the solution. Furthermore, when it comes to animal welfare, it is not ethically acceptable. We promote a holistic approach: a global and comprehensive view of the issue. What will we try to do? Well, maintain farms in excellent condition in terms of facilities, environment, and biosecurity to keep diseases from entering. Producers and exporters in Chile have many advantages because the country is a phyto-zoosanitary island in terms of introduced diseases.

For an epidemiologist, it’s an island, because you have the ocean on one side and the Andes Mountains on the other; the Atacama Desert to the north and native forest to the south. In Spain, it’s harder. So, the strategy is having very good farms with excellent biosecurity standards to prevent the entry of new diseases (or bacteria with resistance genes). All of this with the aim of using fewer antibiotics. Another critical issue is to have healthy genetics. This is clear to poultry farmers because they have been working with the same genetic lines for many years, and in that sense, they are free from many diseases. Now that this is resolved, we still have the diseases we cannot eradicate because animals are carriers by nature; however, we can apply vaccines to control diseases. Therefore, another strategy is to control resistance through vaccination against everything we have. In summary, the idea is to have healthy animals, in excellent farms with extraordinary biosecurity, and to apply vaccination strategies. And once all of this is resolved, we must try to use the smallest amount of antibiotics or look for new alternatives such as herbal medicine with antimicrobial properties. The idea would be to use as many alternatives as possible, and when there is no other choice, the last resort would be choosing the most appropriate antibiotic for each clinical case. This is necessary to optimize the use of these drugs, but it is also necessary to have data to use them in the best possible way, which is what ChileCarne is currently trying to promote.

In Spain, 90% of fattening animals in poultry farming have not received any antibiotics when they go to the slaughterhouse, and the resistance level is surely at a minimum. All variables are well managed and controlled. The pathology remains only in its minimal expression, limiting the use of antibiotics because they are hardly ever needed. In pigs, we have not gotten there yet; there are companies that have farms in very good conditions but others that do not. Without question, we need to improve biosecurity. In Spain, chickens are doing much better than pigs. Another important issue to address and take into consideration is water quality in farms. Ultimately, our goal is for our animals to be in the best conditions and use as few antibiotics as possible; and when we do need them, the idea is to use the latest technology and follow the applicable legislation.


Good Health Program in the Chilean white meat industry

Since 2016, the Association has been developing the “Good Health Program” in the white meat industry in order to promote the responsible and prudent use of antimicrobials in poultry and pork production in line with the guidelines of WHO, the World Organization for Animal Health (OIE), and the Food and Agriculture Organization of the United Nations (FAO). The program includes five pillars of action:

  1. Industry awareness and training.
  2. Promoting the proper use of antimicrobials.
  3. Promoting best practices for heath and biosecurity.
  4. Support for national legislation.
  5. Investment in research, development, and networks with local and international institutions.

Also, as part of the second pillar, and with the advice of Dr. Lorenzo Fraile of the University of Lleida (Spain), the Chilean Meat Exporters’ Association, ChileCarne, has launched the “Surveillance Program for Pathogenic Bacteria Resistance in Poultry and Pigs” in order to contribute to the responsible and prudent use of antimicrobials, as well as the following objectives:

  1. Support the diagnosis of bacterial diseases that affect the Chilean industry through laboratory diagnosis.
  2. Contribute to identifying antimicrobial susceptibility patterns in pathogenic bacteria that affect the Chilean industry.
  3. Promote antimicrobial prescriptions based on antimicrobial susceptibility analysis and the recommendations from WHO, OIE, and EMA.