11.4 How does livestock production affect risks from antibiotic resistance?

11.4.1 How are antibiotics used in livestock production?

As is the case with humans, antibiotics are often over-used or misused in the livestock sector. However, a key distinction when it comes to livestock production, is that antibiotics are deliberately given to healthy animals, and so are used for non-medical purposes (Figure 26).

Figure 26: Uses of antibiotics in livestock. Redrawn from O'Neil. 2016.

 

Treatment of disease

Veterinary use of antibiotics to treat disease after it has arisen, and in order to maintain animal welfare, is a necessary part of all forms of livestock production (including aquaculture) and provides tremendous benefits.

Following diagnosis, treatment involves high doses of antibiotics over short periods of time, given to individual animals so as to completely kill off bacterial pathogens.

Prevention of disease spreading (metaphylactic use)

Where one animal in a herd / flock is found to have a bacterial infection, antibiotics are commonly administered to all animals to stop its spread. This is known as metaphylactic use of antibiotics. High doses are given for relatively short periods in order to completely kill off bacterial pathogens in the entire herd / flock.

Growth promotion

A widespread practice in intensive livestock production is to provide healthy animals with constant low doses of antibiotics as a means to raise the conversion efficiency of animal feed into animal growth, and so increase overall profitability.

How antibiotics act to increase growth is not well understood but may result from reduced low-level infections. This hypothesis is supported by observations of little additional benefits from their use in terms of growth enhancements, where production has been optimised in other respects such as for hygiene, nutrition, and biosecurity.

Preventative use (prophylactic use)

Continuous provision of antibiotics to healthy animals at doses below those used to treat disease is another common practice in intensive livestock production, that is used to prevent infection. As with growth promoters, they are delivered continuously via the animals’ feed and water.

Trade-offs: production intensity, antibiotic use, and producer costs

A key cost for livestock producers is managing disease. This is particularly problematic for more intensive production methods (including aquaculture), which tend to increase animals' susceptibility to infection (Section 11.2.5).

To reduce productivity losses from bacterial infections there are three major options:

  1. Use antibiotics to prevent infections (growth promotion / prophylactic use);
  2. Prevent infections through better hygiene, biosecurity, and animal welfare;
  3. Use antibiotics to treat infections that arise (treatment / metaphylactic).

Non-therapeutic (i.e. growth promotion) and sub-therapeutic (i.e. preventative) uses of antibiotics are not always necessary, even for more intensive models of production. This is demonstrated by the example of some European Union countries where their use for growth promotion has been phased out for over a decade (30 years in Sweden), and where antibiotic use is less than half the global average per kg of animal.

Denmark, for example, cut antibiotic use in both swine and poultry (per animal), while increasing overall levels of pork production, and with only minimal changes to the cost of producing a pig (~1%) (Figure 27).

Figure 27: Antibiotic consumption and millions of pigs produced in Denmark, 1994-2015. Notably as antibiotic use for growth promotion decreased other uses increased, but still dropped overall. Reproduced from Price, et al. 2017.

However, organic pork production in Denmark still uses ten times fewer antibiotics – illustrating the role that production systems as a whole play in controlling the burden of disease in livestock and the corresponding level of antibiotics needed.

Yet even in leading EU countries, managing disease in intensive production systems while also reducing antibiotics has encountered difficulties, resulting in greater antibiotic use for prophylactic, metaphylactic and treatment purposes, until farming and regulatory systems adapt sufficiently (Figure 28).

Figure 28: Sales in active ingredients of Antimicrobials for food producing animals and exports of meat productions in the Netherlands. Reproduced from Elliot. 2015.

Replicating, elsewhere, the approach taken by leading EU countries presents serious challenges. The investments, technology, monitoring systems, and improvements to farm management needed to raise levels of hygiene, biosecurity, and animal welfare are not necessarily cheap or easy – especially for smaller scale producers.

For this reason – and in the absence of legislation and government support – many food producers worldwide choose the cheapest and easiest means at hand to manage the risk to their businesses from bacterial infection: antibiotics.

An additional related problem, is that without as sufficient incentive to reduce antibiotic use, there is also little commercial incentive to produce effective alternatives to antibiotics (e.g. vaccines), thus perpetuating reliance upon antibiotics as a means of disease control. 

11.4.2 What is the extent of antibiotic use in livestock production?

Comprehensive data on the use of antibiotics in livestock are very limited. Even in high-income countries, monitoring of antibiotic use in agriculture has been weak – often consisting of only national level sales data for antibiotics and not differentiated by species or production system.

Nevertheless, the use of antibiotics in livestock production is known to be common worldwide – especially in regions where intensive livestock production is more prevalent (Figure 29).

Figure 29: Global antimicrobial use in food animals. Reproduced from Van Boeckel, et al. 2015.
 

Modelling studies suggest that global consumption of antibiotics by the livestock sector accounts for at least two-thirds of all antibiotics produced worldwide, and in locations where data exists, such as Europe and the United States, their total use in animals tends to exceed that found in humans (when measured by weight).

Among livestock, most antibiotics are used in intensively farmed species such as pig and poultry production, and less so in extensively farmed species such as cattle and sheep.

As much as 30 to 90% of antibiotics consumed by animals are released in urine and manure, and so may come to pollute the environment through their spreading on land and release into waterways.

Data on antibiotic use in aquaculture is even poorer. Specific studies show that their use in aquaculture systems as compared to other livestock systems, ranges from very high to very low, although the overall amount is unclear. Antibiotics are also frequently given to companion animals (i.e. pets).

Trends indicate that global use of antibiotics in the livestock sector is projected to grow by 67% in 2030 mostly taking place in low income countries (Figure 30). Most of this is because of the growth in overall animal numbers (Section 11.2.2), in turn, driven by increasing demand for animal-source foods. About a third attributable to the shift towards more intensive production systems.

Figure 30: Estimated antibiotic consumption in high-consuming countries 2010 and 2030 projections. Reproduced from Van Boeckel, et al. 2015. 

11.4.3 How can antibiotic use in livestock production affect human health?

Reservoirs of resistance

Once resistance has emerged, livestock farms become reservoirs of antibiotic resistant bacteria and resistance genes, which can potentially spread to the wider environment and to humans.

The pathways by which this may occur (Section 11.1.2; Figure 31) can be divided into three major routes:

  1. Direct contact with animals and their waste, colonised by antibiotic resistant bacteria;
  2. Foodborne contact via handling and consumption of infected animal products;
  3. Environmental contact with antibiotic resistant bacteria.
Figure 31: Multiple pathways link antibiotic use (green) and antibiotic resistance (pink) in the food-animal and human health sectors. Reproduced from Koch, et al. 2017. Image created by the artist Victor O. Leshyk.

Volumes of antibiotics used

The emergence of antibiotic resistance is correlated with their total use: with each person or animal treated with antibiotics, the risk for emergence, enrichment and spread of antibiotic resistance goes up (Section 11.3.2). 

As a consequenc of this, the very large volumes of antibiotics used in the livestock sector worldwide, constitute a major driver of antibiotic resistance – and so also a potential risk to public health.

The majority of antibiotic use in livestock production is probably used for intensive production. However, evidence suggests that small scale livestock production can also transmit resistance to humans.

Dosage and duration of use

How antibiotics are administered also makes a big difference.

The continuous use of antibiotics in low doses– as widely practiced in intensive production systems for preventative or growth promoting purposes – creates a long-term evolutionary pressure that selectively favours bacterial cells with resistance traits, while not killing them outright.

This method of use also increases the total stretch of time over which resistance could evolve, allowing for a step-by-step path to greater levels of resistance.

Types of antibiotic used

Many antibiotics administered to animals are also those that are used to treat humans and are often are classified as ‘critically important’ to human medicine (Figure 32).

Antibiotics of last resort – meaning they are the only drugs able to treat some infections – have also been routinely included in animal feed as growth promotors in some places. Older antibiotics or those not used in humans can still have a detrimental effect, because resistance developed to these drugs can still help bacteria to resist the effects of more newly developed drugs used to treat humans.

Figure 32: Of the 41 antibiotics that are approved for use in food producing animals by the FDA, 31 are characterised as being medically important for human use. Reproduced from O’Neil. 2016.

Animal health

Beyond humans, the use of antibiotics is also critical for veterinary medicine. The development of resistance in livestock production threatens not only human health but also the health and welfare of animals, and the people that depend on them.

11.4.4 What evidence exists for antibiotic resistance being transmitted from livestock to humans?

The potential pathways linking antibiotic use and resistance in the livestock sector to antibiotic-resistant pathogens in humans, are well understood. But proving each step in the chain of infection can be very difficult to achieve (Figure 33).

Figure 33: Conceptual illustration of AMR spill over from food animals to humans. Redrawn from Graham, et al. 2017.

Antibiotic resistance genes that are observed in human bacterial infections, may previously have been passed between several different species of bacteria, and may have been altered during this journey – making it extremely challenging to trace their original source.

Nevertheless, although the size of the risk is hard to quantify, growing direct and indirect evidence shows a link between antibiotic use in animals and antibiotic resistance found in humans.

A comprehensive review has found that reduced antibiotic use in livestock is linked to reduced presence of antibiotic resistant bacteria in livestock, and some evidence suggesting reduced rates in human populations – particularly those with direct exposure to livestock.

On this basis, the World Health Organisation has recommended an overall reduction in use of all classes of medically important antimicrobials in food-producing animals, and their complete restriction in food-producing animals for purposed of growth promotion and diseases prevention, and before a diagnosis has been made.

As early as the 1990’s evidence for the presence of a risk was deemed sufficient for some countries to ban the use of antibiotics for growth promotion, with a total European Union ban taking place in 2006. The underpinning research for the legislation showed that:

  • Low-dose, nontherapeutic use of antibiotics selects for resistance to those antibiotics;
  • Resistance genes disseminate via the food chain into the intestinal flora of humans.

Many studies show correlations between antibiotics use in livestock production and levels of resistant bacteria observed in food and in humans. Figure 34, for example, shows the rapid decline in levels of antibiotic resistant bacteria found in retail chicken and in humans, following the withdrawal of an antibiotic drug from chicken production.

Figure 34: Prevalence of ceftiofur resistance (moving average of the current quarter and the previous 2 quarters) among retail chicken Escherichia coli, and retail chicken and human clinical Salmonella enterica serovar Heidelberg isolates during 2003–2008 in Québec, Canada. Reproduced from Dutil, et al. 2010.

In addition to the foodborne pathway, transmission of resistance via direct exposure to animals and their immediate environments (e.g. farms), has been extensively documented among those in occupations such as farm workers, veterinarians, and butchers – and in their families and local communities.

The disposal of manure or effluent, farm waste, and the release of particulate matter in the air, can pollute the wider environment by dispersing antibiotics, antibiotic resistant bacteria, and so also resistance genes – albeit at much diluted levels (Figure 35).

Figure 35: Conceptual framework for understanding the flow of resistance genes across microbiomes within food animals, the environment, and human populations.  Reproduced from Davis, et al. 2011.

While a link between antibiotic use in agriculture and the spread of antibiotic resistance to soils and waterways has been demonstrated, antibiotic resistant infections in humans arising via this pathway have not been proven. Given the complexities in tracing such a route, the risk it presents may in practice be unknowable, which is not to say that there is no risk.

11.4.5 What can be concluded about the health risks from antibiotic use in the livestock sector?

Antibiotics are widely used in the livestock sector with a corresponding rise in antibiotic resistance found in livestock populations. The available evidence is also compelling for the transmission of antibiotic resistance from livestock to humans taking place via foodborne and occupational exposure to resistant bacteria.

However, antibiotic resistant bacteria transmitted to humans from livestock are not necessarily specialist human pathogens, and the transfer of resistance genes to human pathogens, while possible, isn’t entirely straightforward. Evidence for sustained onward transmission between humans of pathogenic bacteria that have acquired their resistance from bacteria previously infecting livestock is limited.

Very little data exists with which to estimate the overall proportion of antibiotic resistant infections in humans that are attributable to livestock, and to some extent it may be unknowable. This lack of understanding means that it is not currently feasible to accurately quantify the benefits to human health from reduced use of antibiotics in animals.

This is problematic in terms of managing risks to human health and weighing up appropriate responses. In particular, because reducing antibiotic use in agriculture has proved difficult to date, and will inevitably have repercussions for animal health, welfare, and productivity, in the absence of major changes to the organisation of livestock production systems. Such changes would, in turn, have significant implications for farmers, food prices and ultimately consumers.

As a point of comparison, human use and misuse of antibiotics – although lower overall in terms of total volume – is thought to pose an overall greater risk to human health, by driving the emergence of resistance in bacteria already well adapted to human hosts, and in contexts where they can more easily be spread between humans (i.e. hospitals) (Figure 36).

Figure 36: The role of modifiable drivers of antimicrobial resistance: a conceptual framework. Subjective assessment of relative contributions by authors of review. Redrawn from Holmes, et al. 2015.

But lower probability events with high impacts – such as the emergence of resistance in human specialised pathogens originating from bacteria linked to livestock – can still pose signification health risks. Especially when considering the huge scale of animals and antibiotics involved in livestock production, and the demonstrable transmission pathways that exist.

Moreover, antibiotic use in the livestock sector is expected to grow, especially in poorly regulated regions, increasing the risk of the emergence and transmission of resistance further.

For many, delaying action due to uncertainty about the precise level of risk, is seen as an unnecessary gamble on public health, considering the potentially irreversible impacts. And for this reason, many governments, institutions and food businesses have committed to taking precautionary action by reducing unnecessary uses of antibiotics in agriculture, and the food system more generally – as well as in human healthcare.

For example: