Antimicrobial resistance in animal production

1. How do bacteria become resistant to antimicrobials and antibiotics?

Most antibiotics in clinical use are naturally produced by soil microorganisms, and these microorganisms are also the source of many of the resistant genes that are found in clinically-relevant bacteria. Resistance to antimicrobials and antibiotics can be linked to the structure of the bacteria, like in the case of some bacteria that have an outer membrane that penicillin G cannot penetrate, or consecutive to a mutation in a metabolic gene that will change the way the cell works to provide resistance to antibiotics. This last type can eventually be transferred to other bacteria.

There are five broad categories of mechanisms that bacteria use to resist to antimicrobials:

• decreased accumulation of the antimicrobial within the cell, either through diminished permeability of the bacterial cell and/or active expulsion (or efflux) of the antimicrobial from the bacteria;
• enzymatic modification or degradation of the antimicrobial;
• genetic acquisition of metabolic pathways alternative to those inhibited by the antimicrobial;
• modification or protection of the antimicrobial target;
• overproduction by the bacteria of the target enzyme of antimicrobials.

Resistance genes can provide bacteria with an evolutionary advantage in relation to other competitors in the same ecological niche, as long as the resistance does not result in a negative impact on the bacteria’s physiology.

2. Can antimicrobial resistance move from animals to humans?

There is a substantial body of evidence to support the view that the emergence of antimicrobial resistance in bacteria in livestock populations is connected to the emergence of resistance in bacterial populations that colonize and infect humans.

However, it seems that the majority of the emergence of resistance in bacteria in humans originate from other bacteria in humans and the same holds true for resistance in animals.

3. What drives the emergence of antimicrobial resistance in animal production?

The widespread excessive use and the misuse of antimicrobials and antibiotics are recognized to be two of the major drivers for acquired resistance in bacterial populations. The use of antimicrobials in health care, agriculture, horticulture, aquaculture and industrial settings has an impact on the expression, selection, persistence and transfer of resistance traits in bacterial populations, due to the selection pressure imposed on the human and animal microbiota, and on environmental bacteria.

Antimicrobials are indeed commonly used non-therapeutically in livestock production as a kind of additional “insurance” to other animal disease risk-management measures, which are commonly used in modern animal production to reduce the risk of introduction and spread of infections in herd. These management measures include vaccination, limited co-mingling, adequate ventilation and temperature controls, biosecurity, appropriate nutrition and housing, and quality-assurance programs. In animal production, the prolonged use of antimicrobial growth promoters at subtherapeutic levels in large groups of livestock, which is known to encourage the emergence of resistance, is still currently common practice in many countries.

The crucial risk factor for the emergence of antimicrobial resistance is the presence of antimicrobial residues derived from these anthropogenic, industrial and agricultural usages in the aquatic and terrestrial environments as these contribute to selection pressure on environmental bacteria and commensal and pathogenic bacteria present in the gut microbiota of farmed animals.

Nevertheless, we need to know much more about the impact of the use of antimicrobials on the spread of resistance into the environment in different types of agricultural production systems, and in particular from low- and middle-income countries.

4. How can resistance pass from animals to humans?

Any mechanism that helps spread bacteria has the potential to transfer resistant bacteria. Both pathogenic and non-pathogenic resistant bacteria can be transmitted from livestock to humans via food consumption, or direct contact with animals or their waste in the environment. If resistance develops in environmental bacteria, this can create an animal or human health problem when such bacteria contaminate water, food crops or animal feed, thus introducing the opportunity for bacterial mixing with commensal or pathogenic species in the animal or human gut.

Resistance may also be conferred by the exchange of genetic elements between bacteria of the same or different strains or species. Such transfer can occur in any environment where resistant bacteria have the opportunity to mix with a susceptible bacterial population, such as in the human or animal gut, in slurry spread on agricultural soil, or in aquatic environments.

5. Can the further spread of antimicrobial resistance be mitigated or stopped?

Recent changes in the global patterns of trade in agricultural products have influenced the patterns of spread of bacteria and therefore the spread of antimicrobial resistance around the world.

Reduction of numbers of resistant bacteria may only be possible if these are outnumbered by susceptible bacteria in an antimicrobial-free environment in which only a small number of individuals have been exposed to antimicrobials, or in the presence of a limited “selection density”.

However, even if the selection pressure imposed by the use of antimicrobials was completely removed this would not necessarily stop the emergence and circulation of resistance. This is an “easy to get and hard to lose” problem because resistance is very difficult to reverse due to the ability of genetic transfer elements to adapt to new hosts and new environments.

In low- and middle-income countries, the present situation of high antimicrobial use together with inadequate resources and infrastructure to ensure rigorous hygiene during slaughter and meat processing, do present significant challenges.

Improved hygiene and biosecurity (e.g. by applying Hazard Analysis Critical Control points protocols: HACCP) should be a major focus for all types of animal production systems so that the risks of introducing pathogens and resistance genes – and the spread of these within animal populations – can be reduced. Future development of quickly biodegradable antimicrobials could help reduce environmental contamination.

Mitigation strategies are thus possible but they require a joint approach based on agricultural, medical and environmental interests. Because livestock, humans and the environment are intimately connected, it is important to consider the emergence and spread of resistance from a “One Health” perspective, which provides a framework for an interdisciplinary approach to deal with this enormous challenge.