Antibiotic resistance – a complex issue and serious threat

Antimicrobial resistance is a complex issue. A recent symposium on the subject stated that “if you think you understand antimicrobial resistance, it hasn’t been explained properly to you.” It is also a global threat that leads to tens of thousands of deaths and millions infected every year, costing the public health care systems in the EU €1.5 billion per year. The spread of resistant bacteria occurs naturally, but also through human actions, in animal agriculture and medical practice. Therefore, responsible use of antibiotics is absolutely necessary and regulation is needed. However, in some countries it is common practice to use antibiotics on healthy animals, in order to prevent disease and infection and to promote growth, and between 30-60% of the antibiotic prescriptions in human medicine are inappropriate.

A global health threat

According to a white paper from a recent symposium on antibiotics states that “the science behind the emergence, amplification, persistence and transfer of antibiotic resistance is highly complex and open to interpretation—and sometimes misinterpretation—from a wide variety of perspectives and misuse. If you think you understand antimicrobial resistance, it hasn’t been explained properly to you.”

It is also a global threat. The Center for Disease Control and Prevention (CDC) reports that in the United States more than two million people get infections that are resistant to antibiotics every year, and at least 23,000 people die as a result. The EU estimates that 25,000 deaths per year are directly linked to resistant bacteria, costing public health systems an estimated €1.5 billion, according the European Centre for Disease Prevention and Control (ECDC). New forms of antibiotic resistance can cross international borders and spread between continents easily, and many forms of resistance spread with remarkable speed. World health leaders have described antibiotic resistant microorganisms as ‘nightmare bacteria’ that ‘pose a catastrophic threat’ to people in every country in the world.

Where and why do antimicrobial resistant bacteria develop and spread?

Because antimicrobial resistance occurs naturally, we will never eliminate it. However, since it also occurs through human actions, whether in animal agriculture or medical practice, we need to work to control the growth of antimicrobial resistance. This is not a problem that will be solved by finger-pointing and blame-shifting but rather through the collaborative work of many to seek honest answers and try solutions.

Animal agriculture

Determining where and why antimicrobial resistance develops and spreads is important to be able to reduce the level of resistance. There are many opportunities for spread of resistance within the food production system, and many people are pointing the finger at animal agriculture. It is important to remember that antimicrobial agents play an indispensable role in animal health and welfare management. Contrary to the use of antibiotics in human medicine, veterinary drugs are limited by label requirements indicating the dose, route of administration, and length of treatment. Most commonly, antibiotics are given to control infectious diseases, but antibiotics may also be given to prevent infectious diseases. However, the Natural Resources Defence Council (NRDC) estimates that 80% of antibiotics sold in the US are used on animals, and that 80% of those are used on healthy animals, in order to prevent disease and infection and to promote growth. For instance, it has been the standard recommendation to infuse broad-spectrum antibiotics into all four teats of all dairy cows at the time they are dried off to help control udder infections. These recommendations are now being revised, and in some countries preventive use of antimicrobial treatment is no longer permitted.

Use in humans

Antibiotic use in human medicine does not have label limits. Individual doctors specify the drug use, dose, length of treatment and more, and doctors sometimes prescribe antibiotics when antibiotics are not indicated. It has been reported that up to 50 percent of antibiotic prescriptions in human medicine are inappropriate, including improper dosing and use of broad-spectrum antibiotics as first-line treatments. Studies also have shown a high rate of antibiotics prescribed for colds and other viral sicknesses, largely due to patients pressuring their physicians to prescribe something when they feel sick. Studies have shown that 32 percent of patients believe taking an antibiotic during a cold prevents more serious illness and 48 percent expect to take antibiotics for a cold.

Other ways resistance might spread

Not only are antibiotics used in humans and animals, antibiotics may also be used in the production of fruits and vegetables and in aqua species. Indirect dissemination of antibiotics in the environment may also occur through excretion of waste by humans and animals that receive antibiotics. These direct applications and indirect dispersals of antibiotics in the environment are other risk factors for the development of resistance.

The need to feed the world

The issue of antimicrobial resistance has to be seen in the context of world agriculture facing the challenge of feeding a global population estimated to be 9 billion people by 2050. Consequently, an evaluation of antimicrobial resistance involves balancing risks of antibiotic use vs. the need to feed the world. Finding alternative strategies to prevent and control animal disease has therefore become a global issue and a critical component of the efforts to alleviate poverty and world hunger.

It is important that agricultural producers, who operate businesses with traditionally slim profit margins, are not subjected to costly measures to reduce the risk of spreading resistance, without knowing if these measures or regulations will actually make a difference for antimicrobial resistance.

Consumers

Consumers are more concerned with food production issues than they were a few years ago, which of course affects animal agriculture. 705 panelists participating in a recent consumer survey from the US said that when buying dairy and eggs 57% thought it was important or very important to know if the animals received growth hormones, 52% thought it was important or very important to know if the animals received antibiotics. 34% thought that knowing the potential impact on the environment from producing the product was important or very important. Consumers in Europe has shown even more concern than what the US survey showed.

The “One-health” approach

The solutions to the problem of resistance will not be simple, and it will require scientists and practitioners in human and veterinary medicine to work in a common direction. This issue requires what has been termed a “One-Health” approach – the collaborative effort of multiple disciplines to attain optimal health for humans, animals and the environment. An organization called One Health Commission is working to do just that, with the mission of “establishment of closer professional interactions, collaborations, and educational and research opportunities across the health sciences professions, together with their related disciplines, to improve the health of people, animals, plants and our environment."

The pace of antibiotic development has slowed down in recent years, as a result of more research data being required to increase safety and decrease unanticipated consequences. The slower approval process has meant that very few antibiotics have been approved either for human use but especially for animal medicine.

Alternatives to Antibiotics

For antibiotics to be replaced there must be alternatives that achieve the same or better results. New methods for treating infectious diseases are being explored, some of which use new technology and others examine old practices that have a degree of effectiveness. This work is being done around the world and was also discussed at an international conference on Alternatives to Antibiotics held in Sept. 2012 in Paris, France.

Some examples of alternatives to antibiotics:

Vitamin D - a natural remedy that can delay and reduce the severity of mastitis infection in dairy cattle. Animals treated with vitamin D had shown in a study to have a significant reduction in bacterial counts and fewer clinical signs of severe infection than untreated cows. In the early phase of the infection, as vitamin D reduced the bacterial counts, milk production was greater in the treated animals than in the untreated ones.

• Enzymes known as ‘endolysins’ have molecular domains that can be isolated and will act independently of their protein surroundings. They can be shuffled like cars in a train, resulting in an antimicrobial that targets just the pathogens of interest, significantly reducing the odds that non-targeted bacteria will develop resistance.

• The antibiotic nisin occurs naturally in milk, and is a product of bacteria resident in the cow’s udder. It helps keep milk from spoiling and kills a broad spectrum of bacteria that cause food-borne illness, most notably listeria and clostridium. It was approved as a food additive in 1969, and since then has become prevalent in the food industry in more than 50 countries.

Responsible use - improved antibiotic stewardship

Perhaps the most important action needed to really slow the development and spread of antibiotic-resistant infections is to change the way antibiotics are used. Up to half of the antibiotic use in humans and much of antibiotic use in animals has shown to be unnecessary. The commitment to always use antibiotics appropriately and safely —only when they are needed to treat disease – and to choose the right antibiotics and to administer them in the right way in every case is known as antibiotic stewardship.

There are examples of more restrictive regulations concerning the use of antibiotics that works well. Norwegian, Swedish and Finnish dairies average very low somatic cell counts, they dry-treat teats individually on a selective basis relying on culture work and infection status history and focus heavily on preventive approaches rather than wholesale treatment approaches.

At the “Bridging the Gap between Animal Health and Human Health” symposium it was concluded, among other things, that there must be an open dialogue around this issue, with animal agriculture at the table, or change can be drastic and by statute and there will not be a deliberative policy change. Food animal production should enforce current regulations and address any antibiotic misuse or there is a risk for unfavorable outcome. Significant efforts are being led by the public health community to reduce inappropriate antibiotic prescribing in human health and reduce hospital-acquired infections. Agriculture needs to be open to change as well.

Dairy production and antibiotic use

The majority of antibiotics used in dairy herds are related to udder health, of which two-thirds are used in dry cow therapy. (The risk of udder infections is high when the cow ends her lactation in order to get ready to calf, and it is therefore common practice to treat these dry cows with antibiotics immediately after the last milking to prevent infections.) Because of the preventive character of dry cow antibiotics and the large potential reduction in antibiotic use, it was suggested during the National Mastitis Council annual meeting in January 2014, that the blanket dry cow therapy (DCT) recommendation (treating all teats on all cows) needs to be reconsidered.

In some countries, like the Netherlands and in the Scandinavian countries, preventive use of antibiotics is no longer permitted, and they practice selective dry cow therapy. They have also reduced the use of antibiotics on farms considerably.

At the NMC annual meeting the following suggestions were presented:

• Mastitis treatment decisions should be based on knowledge of the cause of the disease. This can lead to a reduction of antibiotic use on dairy farms by as much as 50% for the treatment of mild and moderate clinical mastitis, without any negative effects on the efficacy of the treatment or the long term health and production potential of the cow. Dairy farms could save considerably on treatment-related costs such as discarded milk, drugs and labor. It can also contribute to a reduction of the potential risk for development of antimicrobial residues in milk.

• There is a potential relation between antibiotic use in the udder and antibiotic resistance in intestinal bacteria through the feeding of waste milk to calves. Milk produced during the withdrawal time is unfit for human consumption, and is often fed to calves. Approximately 70% of samples contain antibiotic residues, often in low concentrations, and thus can lead to selective pressure in intestinal bacteria in calves. The same may be true for antibiotic residues of dry cow antibiotics in colostrums.

• Some of the so called ‘third preference’ antibiotics are not excreted in the udder, and don’t require a withdrawal period for milk and for that reason making them an attractive alternative, and they have therefore been used intensively. Evidence exists that the use of third preference antibiotics can lead to increased resistance, and based on the possible consequences on human and animal health care, antibiotics of third preference should only be used when there are no other alternatives.

• Internal teat sealants have shown to be a potential alternative to prevent low SCC cows from new intramammary infections in the dry period.

Read more about antimicrobial use in dairy, and selective dry cow therapy here.

Terry Dwelle, MD, state health officer of North Dakota, spoke at the National Institute of Animal Agriculture’s antibiotic conference and offered the following suggestions for minimizing the risk of antibiotic-resistant pathogens in livestock production:

• Use antibiotics only when indicated.

• Use the least broad-spectrum products first.

• Use antibiotics for the least amount of time possible – This decreases the time organisms have to develop resistance mechanisms.

• Use adequate therapeutic doses.

• Use antibiotics not important to human medicine whenever possible.

• When using “crossover drugs,” manage their use for the least impact on human health.

• Appropriately monitor cultures and sensitivities to detect signs of resistance.

Antibiotic use in animal agriculture should always be done in consultation with a veterinarian, and dairy producers are encouraged to have a valid veterinary-client-patient relationship (VCPR) through which all issues of herd health and treatment are discussed. Veterinarian involvement has been shown to reduce the incidence of antibiotic residues in animals that leave the farm.

Links

Sweden uses the fewest antibiotics in food production

The bacterial challenge: time to react. A call to narrow the gap between multidrug-resistant bacteria in the EU and the development of new antibacterial agents

Communication from the Commission to the European Parliament and the Council Action plan against the rising threats from Antimicrobial Resistance

Centers for Disease Control and Prevention: Report on Antibiotic Resistance Threat 2013

CDC warns of 'catastrophic' results of increased drug resistance (The Guardian)

Case Study Asks What Is Important To Consumers

Common-sense antibiotic use (Dairy Herd Management Network)

NIAA (National Institute for Animal Agriculture) 2013 Antibiotics Symposium Proceedings "Bridging the Gap Between Animal Health and Human Health"

Strategies That Work - Alternatives to Antibiotics in Animal Health

New antibiotic could make food safer and cows healthier

USDA: Alternatives to antibiotics

Milkproduction.com: Antibiotic resistant bacteria issue demands action (Part 1)

Milkproduction.com: What is antimicrobial resistance? (Part 2)

Milkproduction.com: Where does antimicrobial resistance come from? (Part 3)

Milkproduction.com: Moving forward with antimicrobial resistance (Part 4)

WHO: Tackling antibiotic resistance from a food safety perspective in Europe

EFSA Antimicrobial Resistance page

EFSA (European Food Safety Authority) infographic

Author

Monica Wadsworth

Monica Wadsworth
85 articles

Writer at Milkproduction.com

Read more »

Milkproduction.com

Milkproduction.com