Antibiotic resistance: What is it and why is it important?

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The first use of antibiotics as a growth promoter in livestock was in the late 1940s when the use of chlortetracycline fermentation waste was found to enhance the growth of poultry, pigs and other species.

Intensification of livestock production was increasing then and the use of broad spectrum antibiotics was shown to control the diseases, especially respiratory and enteric conditions commonly found in intensive production systems. Often these antibiotics were given at doses well below what would be used to treat an ill animal. This is called a sub-therapeutic dose.

Antibiotic resistance to livestock disease became apparent in the 1950s. Growing fears over its public health implications led MAFF to appoint a Committee of Enquiry into the use of antibiotics in animal husbandry and veterinary medicine.

Chaired by Professor Swann, Bristol University, it reported in 1969 that rising rates of multi-drug resistant bacteria were due to agricultural use, particularly the sub-therapeutic dosage being used as a growth promoter. This led to the end of antibiotics being used as growth promoters in animals and use permitted only for treatment of illness.

Antibiotic resistance makes bacterial infections and infectious bacterial diseases in humans and animals harder to treat with antibiotics. The UK’s Chief Medical Officer, Dame Sally Davies, said in her annual report published in March, 2013: “Antibiotic resistance is one of the greatest threats to modern health and we face a future without cures for infection if antibiotics are not used responsibly”

What is an antibiotic?

Technical definition: Antibiotic was the term originally applied to naturally occurring compounds, such as penicillin, which attacked infecting bacteria without harming the host. ‘Antibiotic’ is now regularly used to refer to synthetic compounds as well as natural compounds, and to refer to antiviral as well as antibacterial drugs.

In the public mind, however, ‘antibiotics’ are still largely equated with penicillin.

What is antibiotic resistance?

Resistance is the ability of bacteria to grow or survive in the presence of an antibiotic at levels that are usually sufficient to inhibit or kill bacteria of the same species

LP Garrod wrote in 1968: “No one recently qualified, even with the liveliest imagination, can picture the ravages of bacterial infection which continued until little more than 30 years ago.”

Since 1968, many new antibacterial agents have been developed and antiviral chemotherapy, then in its infancy, has become possible for an increasing range of viral diseases. As well as its uses in the direct treatment of infection, antimicrobial chemotherapy has also helped to make possible medical advances, such as transplantation and the treatment of many forms of cancer which carry a special risk of infection.

Things started to go wrong in the early days of antibiotics when, during the development of penicillin, the enzyme which destroys it was isolated and it was predicted that penicillin resistance would become a problem. So it has and so, also, at greatly varying intervals following its introduction, has resistance to each new antibiotic.

In the UK, the aspect of antibiotic resistance most talked about among the public at large is probably MRSA (methicillin-resistant staphylococcus aureus), an infection associated principally with hospitals and nursing homes.

It is now known that all antibiotic resistance has a genetic basis. Some organisms are naturally resistant to many antibiotics (innate resistance). This probably evolved as a response to exposure to antibiotics present in the natural environment.

Many such organisms pose no threat to healthy people, but may become important infections in vulnerable patients in hospital. Examples include the pseudomonas species and some bacteria found in the bowel, such as e-coli.

Is antibiotic resistance in humans and animals the same?

Today, antibiotic resistance leading to treatment failures in veterinary medicine occurs, but it is less frequently reported than in human medicine. Comparing human and animal resistance levels is difficult because different ways for measuring resistance levels are often used and they are not comparable.

What causes antibiotic resistance?

The consensus amongst experts is that the main cause of antibiotic resistance in human bacterial infections is the overuse and/or inappropriate use of antibiotics in human medicine.

This could include prescribing antibiotics for viral infections such as flu and cold where they have no effect on the virus, not completing a course of antibiotic treatment, or prescribing the wrong type for the bacteria involved. Antibiotic resistance occurs in livestock production for similar reasons.

How does antibiotic resistance develop?

It can arise by a number of diverse mechanisms.

First, is mutational resistance. These occur randomly in a small proportion of a bacterial population.

One of the best examples is seen in the human tuberculosis bacterium. A few TB bacteria are naturally resistant to, for example, streptomycin. Where streptomycin was used as a single antibiotic treatment (common in the 1950s) these resistant bacteria soon become the dominant population, thus human TB became resistant to streptomycin.

A second is by the transfer of resistance genes from one bacterium to another. This can happen in different ways.

It can occur by the direct transfer between bacteria of genetic material carried on small pieces of DNA situated within the bacterial cell, or by similar pieces of DNA carried on a bacterial virus, known as a bacteriophage or by direct transfer of a piece of DNA.

These mechanisms have been known for many years. Recent work has identified the frequency and ease with which different bacteria are able to exchange genetic material. The crucial importance of these mechanisms in bacterial evolution is now known, for example, that genetic interchange can take place between a many more types of bacteria than was formerly thought.

It is probably a common event in the natural world. There is a global pool of resistance genes which can spread between different bacterial populations occupying different habitats, eg between man, animals and the environment.

Findings such as this has lead to the development of a new approach called ‘One Health’ (I’ll look at that in another article). One Health looks at a broader picture of our world looking at the interaction between humans, animals (domestic and wild) and the natural environment.

Since the Swann report, the use of antibiotics as growth promoters has been phased out and changes in how antibiotics are used has followed from using antibiotics as blanket treatment to a more targeted approach.

How does resistance spread?

Genes carrying antibiotic resistance factors can spread and multiply if the host bacterium gains an evolutionary advantage in acquiring them, ie it can survive antibiotic treatment.

This is known as selection pressure. The antibiotic kills all non-resistant bacteria, thereby ‘selecting out’ the resistant strain. In this way, a previously minor population of antibiotic-resistant organisms rapidly becomes dominant.

A population of bacteria can be found in an individual animal, a flock or herd, or in the general population of people or animals.

The speed with which resistance to any antibiotic emerges and spreads varies. However, it is indisputable that resistance has developed to many new antibiotics after their introduction, with consequent actual loss of their former value to medicine.

This is a vicious circle repeatedly witnessed during the last half century, in which the value of each new antibiotic has been progressively eroded by resistance, leading to the introduction of a new and usually more expensive agent, only for this in its turn to suffer the same fate.

With livestock, antibiotic resistant bacteria spread can occur within a group, herd, or between farm units by the movement of animals, people or by vectors. A vector is something which can transfer a disease or in this case, an antibiotic resistant bacteria, from one place to another.

Examples can be any of livestock transport, clothing, equipment (like shearing, scanning, contractors, foot trimming), birds, rats, dung or slurry. Even you, the livestock keeper, can be a source if you have an antibiotic resistant infection!

How do bacteria resist antibiotics?

Research shows that resistance arises from five known mechanisms: 1), if the bacteria can inactivate the drug before it reaches its target within the bacterial cell; 2), if the outer layers of the bacteria cell prevent the drug from entering; 3), if the drug enters but is then pumped back out again; 4), if the bacteria has altered and is no longer recognised by the antibiotic; or 5), if the bacteria develop another way of coping with the antibiotic’s target in the bacteria.

Although some hundreds of resistances are known, virtually all can be ascribed to one of these five broad types of mechanisms.

What does this mean for livestock producers?

All livestock farmers must be totally committed to producing safe food. It’s our job.

Producing, processing and selling food carries a legal responsibility to safeguard the health and welfare of animals as the top of the production chain. Livestock must be managed to reduce the risk of disease challenge and, therefore, reduce the need to use antibiotics and other medicines.

It is important to both animals and humans that all efforts are made to ensure the use of antibiotics is designed to be effective and targeted. Antibiotic resistance means antibiotics fail to treat a disease or infection.

Livestock farmers have a strong armoury to meet these responsibilities. First line is a health plan.

Responsible livestock farmers will have drawn up, implemented and regularly review a herd/flock health plan. The reasoning behind these is that the industry can set out, in a manner that can be audited, that it has identified the key diseases and production issues on each unit.

The plan outlines the routine preventive treatments (eg biosecurity, vaccination and worming programmes) and disease control policy which demonstrate how disease incidence is reduced. This, in turn, demonstrates the steps being put in place to reduce antibiotic use.

This is why your veterinary surgeon is involved in drawing up the plan as they are the experts in this process.

Second line is membership of a farm assurance scheme. The logic here is to provide an overview of standards of stockmanship, husbandry, welfare and record keeping. These assessments, burdensome as they may appear, are the key to many doors for the industry.

They provide an assurance for government, retailers and industry that the vast majority of farms meet required standards. Wide membership of schemes helps our member organisations such as NFUS, NBA, NSA, etc, promote and argue for our industry from the basis of sound knowledge

A recent addition to farm assurance is the collation of antibiotic use on the farm. This provides an overview of what antibiotics are being used and why.

A useful addition to this would be for veterinary practices to produce a collation of their practice use to provide a better overview for the industry and regulators.

Why and how antibiotics are used in UK farms?

Antibiotics are used to manage and cure bacterial infections in livestock and in the UK they can only be obtained on a veterinary prescription.

There is a sound reason for this. It ensures that antibiotics are supplied on the basis that the vet has visited the premises at least once every year, therefore is familiar with your production system, is aware of your disease profile and can match the most suitable antibiotic to your needs for each situation.

As antibiotics are only available on prescription, there is an audit of what is being used and to an extent where. I wrote in my column last year about the incredible strides the UK farming industry has made in reducing antibiotic use and still maintained or increased output.

Between 2014 and 2018, antibiotic use in UK farm production fell by 49%. It’s a major success story. There is a similar tale to tell with pesticides. We are an adaptable and resilient industry and more than capable of dealing with the challenges placed before us.

There are three ways antibiotics are used in livestock systems in the UK:

1), Therapy – to treat and cure sick animals when the diagnosis of disease or infection has been made.

2), Metaphylaxis – to control disease spreading in groups of animals where some are already sick. This aims to prevent the spread of disease to other animals in close contact, and thus at risk, which may already be (sub-clinically) infected.

3), Prophylaxis – to prevent sickness or disease developing in a group of healthy animals where a vet has diagnosed there could be a high risk of bacterial infection. Preventive treatment sometimes referred to as prophylaxis, for an animal or a group of animals, before clinical signs of disease, to prevent the occurrence of a disease or infection.

How have we reduced antibiotic use?

In the 1960s through to the 1980s, group treatments were commonplace.

Treatment was dispensed through food or water mainly in pig and poultry systems. In the 1980s, group treatments of cattle and sheep gained ground in response to intensification and increasing farm size.

By the 1990s, many of these diseases were controlled by vaccination or husbandry changes.

Today, with fewer but larger units and more advances in husbandry and housing, there is less need for mass medication and a move to more targeted treatment. The pig industry in particular has made great strides in finding ways of controlling some of the diseases that required mass medication just a few years ago.

Other livestock systems have still to reach this stage of development and innovation but progress is being made with new technologies.

What is ‘responsible use’ in animals?

Antibiotics should be used in farm animals in the following circumstances. Therapy should be given where a bacterial infection is diagnosed.

Preventive treatment with antibiotics in animals should:

• Only be given to animals diagnosed at high risk of bacterial disease on the basis of epidemiological and clinical knowledge from the prescribing vet.

• Only occur under prescription by a veterinarian on the basis of epidemiological and clinical knowledge.

• Not be applied routinely.

• Not be used to compensate for poor hygiene or for inadequate husbandry conditions.

What is not responsible use?

Reducing use by, for example, withholding necessary treatment, using lower than recommended doses or switching to an inappropriate antibiotic because it has a lower amount of active ingredient per dose is not responsible use.

Equally, not estimating the weight of an animal accurately before deciding on the dosage is not responsible. Regular weighing of your stock will provide a good guide to weights.

Measuring antibiotic use

Monitoring antibiotic use and benchmarking is increasingly being carried out by veterinary practices, and some food retailers and milk buyers are placing emphasis on regular reporting of antibiotic usage data

All Red Tractor dairy farms are required to collate antibiotic usage and undertake an annual review of antibiotics with their vet. The dairy industry is investigating antibiotic use with a view to benchmarking usage in age, group, type, location, antibiotic per kg on farm.

When interpreting antibiotic use benchmarking data, it is vital to focus on developing responsible antibiotic use. Herd health planning and strategies to prevent disease are key to reducing the need to administer antibiotics and improving health and welfare on the farm.

Do intensive systems contribute more to the risk than extensive set-ups?

For optimal animal health and welfare, good animal husbandry and biosecurity practices are needed in all farming systems, whether these are intensive, extensive, or organic.

There is no scientific evidence that intensive farming systems contribute more to the overall risk of antibiotic resistance than extensive farming systems.

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