Antibiotic Use in Livestock Farming: History
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Antibiotics are natural or synthetic molecules capable of inhibiting the growth of bacteria (bacteriostatic) or killing some bacteria (bactericidal). Antibiotics are frequent in the livestock industry to prevent and treat diseases caused by bacteria, allowing for healthy growth and reduced animal mortality and morbidity. The use of these antibiotics occurs principally in pigs, cattle, poultry, and the aquaculture industry.

  • antibiotics
  • antimicrobial resistance
  • livestock industry

1. Introduction

Antibiotics are frequent in the livestock industry to prevent and treat diseases caused by bacteria, allowing for healthy growth and reduced animal mortality and morbidity. The use of these antibiotics occurs principally in pigs, cattle, poultry, and the aquaculture industry [5,94] Livestock farmers use antibiotics for metaphylactic, prophylactic, and growth promotion purposes. Metaphylaxis is the administration of drugs to presumably infected or disease susceptible groups of animals to treat and control the disease transmission among animals in close contact. Prophylaxis is the administration of drugs to a group of animals before clinical signs of a disease to prevent its occurrence [95]. Antibiotics also can be used as growth promoters; the destruction of the intestinal microbiota generates increased assimilation of the feed consumed; therefore, an increase in the muscle mass of the cattle occurs fewer times; however, this practice has been banned in some countries [11].
Globally, cattle account for 34% of the world’s dietary protein supply. In 2019, China was the largest consumer of beef, poultry, and pork (71,338 thousand tonnes), followed by the European region (39,862 thousand tonnes), the United States (39,225 thousand tonnes), Brazil (20,956 thousand tonnes), and Russia (9894 thousand tonnes). It has been estimated that 261.906 million tonnes of meat (beef, pork, and chicken) were consumed worldwide in 2019 (https://comecarne.org accessed on 12 April 2022). In Colombia, by 2020, there were 28,245,262 cattle head, 221,011 pigs head, and 463,113 poultry head (https://www.ica.gov.co/areas/pecuaria/servicios/epidemiologia-veterinaria/censos-2016/censo-2018.aspx accessed on 12 April 2022).
According to a report by the FDA between 2009 and 2018, the annual amount of antibiotics used in animals reached 8,000,000 Kg, with tetracyclines being the most widely used [7]. Global consumption of antimicrobials used in food-producing animals was estimated at 63,151 tonnes (http://www.fao.org/antimicrobial-resistance/key-sectors/animal-production/en/ accessed on 12 April 2022).

2. Antibiotics Use in Livestock Farming and Foodborne Diseases (FBD)

According to the WHO, Foodborne Diseases (FBD) are diseases commonly transmitted through the ingestion of contaminated food. FBD involves a broad group of illnesses caused by microbial pathogens, parasites, chemical contaminants, or biotoxins [96]. The severity of these diseases in humans varies from mild to severe symptoms, which require lifelong treatment. It has been estimated that, in industrialised countries, more than 10% of the population could suffer from a disease associated with the ingestion of contaminated food [97]. One of the aspects that increase the severity of FBD is the presence of antibiotic-resistant microorganisms, leading to therapeutic failure in humans. This resistance is directly associated with the use of antimicrobials for prophylaxis, metaphylaxis, or as growth factors during livestock destinated to a source of meat, eggs or milk [98].
In animal food production, the use of antibiotics has increased; for example, 63,151 tons of antibiotics were used in livestock production in 2010, and have been estimated that there will be a 67% increase by 2030 [99].
The scenario tends to be worsened by manure used as a crop fertiliser, leading to increased dissemination of bacteria and antibiotic resistance genes. Disseminated bacteria and resistance genes will have contact with the soil microbiome, which could lead to loss of biomass and a reduction in nitrification, denitrification, and respiration activity, as well as impairment of enzyme activity, such as dehydrogenases (E.C. 1.1.-), phosphatases (E.C. 3.1.3.-), phenoloxidase (E.C. 1.10.3.), ammonium monooxygenase (E.C. 1.14.99.39), and ureases (E.C. 3.5.1.5), considered important indicators of soil activity. The exact amount of antibiotic use in animal production is difficult to define; however, it is higher than hospital use [99,100].
Pathogen entry into the meat supply chain occurs at any stage of production (rearing, processing, distribution, sale, handling, and preparation) [101]; some authors have described the slaughter stage, during the removal of the gastrointestinal tract or intestinal contents, as the principal source of pathogen dissemination by cross-contamination through equipment, utensils and personnel [101,102,103,104,105], increasing the risk of contamination at the production line, considering the ability of some of the microorganisms (Enterobacteria) to generate biofilms [106].
The entry of antibiotics into the meat supply chain occurs in feeding operations, where concentrates contain antibiotics used as growth promoters. However, some EU countries have prohibited antibiotics use as growth promoters (since 2006) because they applied for prophylaxis or metaphylaxis [99,100].
On the other hand, in the meat processing stage, antimicrobial resistances are transmitted through the entry of food contaminated with resistant microorganisms or through the food processing environment. Mentioning a couple of microorganisms, Salmonella spp., and Listeria monocytogenes are two of the most important bacterial agents in FBD.
Salmonella spp., (one of the pathogens transmitted during the slaughter of livestock) is the causing agent of salmonellosis, a disease that has a high morbidity rate in both industrialised and developing countries; causing acute enterocolitis with abdominal pain, bloody or non-bloody diarrhoea, nausea, and vomit [64,106,107]. Transmission of non-typhoidal Salmonella to humans can occur zoonotically through contact with faecal material from carrier animals or by the consumption of contaminated food [64,106,107,108,109].
On the other side, L. monocytogenes (one of the pathogens transmitted during the production of processed foods) is the causative agent of listeriosis, an invasive disease; therefore, needs to cross through the intestinal barrier to gain access to internal organs, the entry takes place through Peyer’s patches by M-cells. Subsequently, the bacterium goes to the liver and may develop granulomatous hepatitis, due to the invasion of hepatocytes. Afterward, the bacterium is internalized, and, in some cases, there is intracellular proliferation and dissemination to other tissues, with tropism for the Central Nervous System (CNS) and the pregnant uterus [110,111,112,113,114].
In developing countries, the main route of contamination is through consumption of contaminated vegetables, contaminated water and human-human contact, whereas in industrialised countries, the major route of contamination is related to ingestion of contaminated food products of animal origin, especially fresh meat and eggs [64,106].
The final food consumer comes into contact with antibiotic-resistant microorganisms through their presence in ready-to-eat meat, dairy and vegetable products [115]. Contact with microorganisms carrying antibiotic resistance genes can lead to two possible scenarios: (i) the modification of the gut microbiome [100], (ii) a potential hazard to human medicine due to the inability to manage infections in the general population, resulting in prolonged broad-spectrum antibiotic treatments, which would end up in a constant loop between resistances going into the environment and the population [99,100].

3. Waste from the Livestock Industry

According to the United States Department of Agriculture (USA), animals confined for food production generate approximately 335 million tonnes of waste per year, exceeding 40 times the mass of biosolids generated by humans [5,8].
The principal cause of bacterial resistance to antibiotics is the disposal of antibiotics in livestock waste in soil, ground and surface water, atmosphere and crops [5,9]. When livestock wastes are disposed of, the antibiotics in faeces are often broken down due to oxidation–reduction reactions, hydrolysis, biodegradation and photodegradation, reducing the concentration of the antibiotic and thus its ability to kill bacteria [116]; which generates a problem, as bacterial exposure to sub-lethal concentrations; favouring the adaptation and proliferation of bacteria with multidrug-resistant phenotypes. Whereas a high proportion of excreted antibiotics are bioactive, consequently, and due to fast bacterial reproduction, the resistance phenotype can easily express Sarmah [8].
Bacteria can resist antibiotics through several mechanisms; through physiological adaptation, bacteria can change membrane transport pumps (porins), excluding harmful agents; however, this mechanism is limited Silbergeld [5]. Another mechanism is mutations, which can alter or eliminate the target of the antibiotic [116], mutations could occur in DNA sequences that modify the production or structure of the enzymes responsible for inactivating the antimicrobial agent; for example, β-lactamases (E.C. 3.5.2.6) can inactivate the β-lactam ring, which is part of the structure of β-lactam antibiotics (Table 1). These enzymes break the amide bonding of the ring, and the generation of acidic derivatives that do not have antibacterial properties occurs by preventing the antibiotics from binding to bacterial carrier proteins [117].
Resistance genes can be shared between bacteria by three different mechanisms (transformation, conjugation, and transduction), thus transferring resistance between pathogenic and non-pathogenic bacteria, this transfer is called “horizontal transfer” and can occur between bacteria of different genera. Vertical transfer occurs during cell division through the genetic material transmission from mother to daughter cell [118].
Conjugation is one of the most effective mechanisms for genetic material transfer and is considered one of the reasons for antibiotic resistance. Conjugation is frequent in Gram-negative bacteria and to a lesser extent in Gram-positive bacteria [119,120]. During the Gram-negative conjugation process, a donor bacterium transfers a plasmid containing resistance genes to a recipient bacterium throughout sexual pilis [120,121]. During the Gram-positive conjugation process, the receptor cells excrete an inducing peptide called pheromones or autoinducers. When a certain level of peptide concentration is reached the donor cell activates the transcription of genes related to the production of aggregation substances, including adhesins and coupling proteins. The donor cell attaches to the receptor cell, which generates a channel to transfer the genetic material [122].
The transduction process, allows resistance genes to be transferred from one bacterium to another mediated by a bacteriophage that has previously undergone lytic cycling in the “donor strain”.
The transformation process occurs when a bacterium incorporates DNA from the environment favoured by the state of competence generated during cell growth [116]. Furthermore, mobile genetic elements, such as plasmids, insertions sequences, transposons, and integrons are responsible for 95% of antibiotic resistance [5].
Bacterial resistance to antibiotics implies the treatment’s failure against infections, the latency of infectious processes, progression of the disease to chronic processes, the transmission of the infection to other animals, outbreaks, economic losses, and even adverse reactions to antibiotics [11]. In many cases, crops for human consumption are fertilised with animal faeces and irrigated with water sources contaminated with antibiotics, resulting in the spread of resistant strains to humans and animals. Spread generates a public health problem, as treatment options against pathogenic bacteria are limited [12].
In the last 20 years, the presence of antibiotics has been documented in different water sources; surface, ground, and oceanic waters [15,123]. In addition to water sources, food contaminated with antibiotics can cause adverse allergic reactions in hypersensitive individuals [11]. Ramírez et al. (2012) administered six antibiotics intramuscularly and intramammary to 115 cows and found that 65.2% of cows had Oxytetracycline (OXT), 58.8% of cows had Tylosin (TLY), 69.2% of cows had Spiramycin (SP) and 65% of cows had Amoxicillin (AMC) traces in milk [124].
The presence of antibiotics in water is a problem for ecosystems; Xu et al. (2019) demonstrated the toxicity of Tetracycline (TE) and its degradation intermediates (anhydrotetracycline and epitetracycline hydrochloride) in microalgae. At high concentrations of Tetracycline (TE) (>5 mg L−1), the permeability of microalgae is affected, showing structural changes and increasing reactive oxygen species (ROS) activity in the water [125].

This entry is adapted from the peer-reviewed paper 10.3390/molecules27144436

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