antibiotic use in livestock antibiotic use in livestock antibiotic use in livestock is the use of antibiotics for any purpose in the husbandry of livestock, which includes treatment when ill (therapeutic), treatment of a group of animals when at least one is diagnosed with clinical infection (metaphylaxis), and preventative treatment (prophylaxis). antibiotics are an important tool to treat animal as well as human disease, safeguard animal health and welfare, and support food safety. however, used irresponsibly, this may lead to antibiotic resistance which may impact human, animal and environmental health. a cdc infographic on how antibiotic-resistant bacteria have the potential to spread from farm animals while levels of use vary dramatically from country to country, for example some northern european countries use very low quantities to treat animals compared with humans, worldwide an estimated 73% of antimicrobials (mainly antibiotics) are consumed by farm animals. furthermore, a 2015 study also estimates that global agricultural antibiotic usage will increase by 67% from 2010 to 2030, mainly from increases in use in developing bric countries. increased antibiotic use is a matter of concern as antibiotic resistance is considered to be a serious threat to human and animal welfare in the future, and growing levels of antibiotics or antibiotic-resistant bacteria in the environment could increase the numbers of drug-resistant infections in both. bacterial diseases are a leading cause of death and a future without effective antibiotics would fundamentally change the way modern human as well as veterinary medicine is practised. however, legislation and other curbs on antibiotic use in farm animals are now being introduced across the globe. in 2017, the world health organization strongly suggested reducing antibiotic use in animals used in the food industry. the use of antibiotics for growth promotion purposes was banned in the european union from 2006, and the use of sub-therapeutic doses of medically important antibiotics in animal feed and water to promote growth and improve feed efficiency became illegal in the united states on 1 january 2017, through regulatory change enacted by the food and drug administration (fda), which sought voluntary compliance from drug manufacturers to re-label their antibiotics. history the 2018 book 'pharming animals: a global history of antibiotics in food production (1935–2017)' summarises the central role antibiotics have played in agriculture: "since their advent during the 1930s, antibiotics have not only had a dramatic impact on human medicine, but also on food production. on farms, whaling and fishing fleets as well as in processing plants and aquaculture operations, antibiotics were used to treat and prevent disease, increase feed conversion, and preserve food. their rapid diffusion into nearly all areas of food production and processing was initially viewed as a story of progress on both sides of the iron curtain." to retrace, while natural antibiotics or antibacterials were known to ancient man, antibiotics as we know them came to the fore during world war ii to help treat war time casualties. it is recorded that antibiotics were first used in farming towards the end of the war, in the form of intra-mammary penicillin preparations to treat bovine mastitis. at that time, milk was seen as an agricultural product which was highly susceptible to bacterial contamination, and farmers welcomed the opportunity to 'purify' their produce for the safety of consumers; it was only later that concern switched from the bacterial load of the product to the residues that might result from untimely or unregulated treatment. the use of antibiotics to treat and prevent disease has followed a similar path to that used in human medicine in terms of therapeutic and metaphylactic applications to treat and manage disease and improve population health, and the application of case-by-case strategic preventative treatments when animals are deemed at particular risk. however, in the late 1940s, studies examining the supplementation of b12 in chicks' diets found that b12 produced from the fermentation of streptomyces aureofaciens, an antibiotic for use in human medicine, produced a better weight gain for chicks than b12 supplied from other sources, and a reduced amount of feed to bring the birds to market weight. further studies on other livestock species showed a similar improved growth and feed efficiency effect with the result that as the cost of antibiotics came down, they were increasingly included at low ('sub-therapeutic') levels in livestock feed as a means of increasing production of affordable animal protein to meet the needs of a rapidly-expanding post-war population. this development coincided with an increase in the scale of individual farms and the level of confinement of the animals on them, and so routine preventative antibiotic treatments became the most cost-effective means of treating the anticipated disease that could sometimes arise as a result. veterinary medicine increasingly embraced the therapeutic, metaphylactic and strategic preventative use of antibiotics to treat disease. the routine use of antibiotics for growth stimulation and disease prevention also grew. growth stimulation in 1910 in the united states, a meat shortage resulted in protests and boycotts. after this and other shortages, the public demanded government research into stabilization of food supplies. since the 1900s, livestock production on united states farms has had to rear larger quantities of animals over a short period of time to meet new consumer demands. it was discovered in the 1940s that feeding subtherapeutic levels of antibiotics improved feed efficiency and accelerated animal growth. following this discovery, american cyanamid published research establishing the practice of using antibiotic growth promoters. by 2001, this practice had grown so much that a report by the union of concerned scientists found that nearly 90% of the total use of antimicrobials in the united states was for non-therapeutic purposes in agricultural production. certain antibiotics, when given in low, subtherapeutic doses, are known to improve feed conversion efficiency (more output, such as muscle or milk, for a given amount of feed) and may promote greater growth, most likely by affecting gut flora. the drugs listed below can be used to increase feed conversion ratio and weight gain, but are not legally allowed to be used for such purposes any longer in the united states. some drugs listed below are ionophores, which are coccidiostats and not classified as antibiotics in many countries; they have not been shown to increase risk of antibiotic-resistant infections in humans. antibiotic growth promoters historically used in livestock production in some countries drug class livestock bacitracin peptide beef cattle, chickens, swine, and turkeys; promotes egg production in chickens bambermycin beef cattle, chickens, swine, and turkeys. carbadox swine colistin swine laidlomycin beef cattle lasalocid ionophore beef cattle lincomycin chickens and swine monensin ionophore beef cattle and sheep; promotes milk production in dairy cows neomycin/ oxytetracycline beef cattle, chickens, swine, and turkeys penicillin chickens, swine, and turkeys roxarsone chickens and turkeys salinomycin ionophore tylosin chickens and swine virginiamycin peptide beef cattle, chickens, swine, turkeys the practice of using antibiotics for growth stimulation has been deemed problematic for these following reasons: it is the largest use of antimicrobials worldwide subtherapeutic use of antibiotics results in bacterial resistance every important class of antibiotics are being used in this way, making every class less effective the bacteria being changed harm humans antibiotic resistance mechanisms for the development of resistance antibiotic resistance – often referred to as antimicrobial resistance (amr) although this term covers anti-virals, anti-fungals and other products – can occur when antibiotics are present in concentrations too low to inhibit bacterial growth, triggering cellular responses in the bacteria that allow them to survive. these bacteria can then reproduce and spread their antibiotic-resistant genes to other generations, increasing their prevalence and leading to infections that cannot be healed by antibiotics. this is a growing matter of concern as antibiotic resistance is considered to be a serious future threat to human welfare. infectious diseases are the third leading cause of death in europe and a future without effective antibiotics would fundamentally change the way modern medicine is practised. bacterial conjugation bacteria can alter their genetic inheritance through two main ways, either by mutating their genetic material or acquiring a new one from other bacteria. the latter being the most important for causing antibiotic-resistant bacteria strains in animals and humans. one of the methods bacteria can obtain new genes is through a process called conjugation which deals with transferring genes using plasmids. these conjugative plasmids carry a number of genes that can be assembled and rearranged, which could then enable bacteria to exchange beneficial genes among themselves ensuring their survival against antibiotics and rendering them ineffective to treat dangerous diseases in humans, resulting into multi-drug resistant organisms. however, antibiotic resistance also occurs naturally, as it is a bacterium's response to any threat. as a result, antibiotic-resistant bacteria have been found in pristine environments unrelated to human activity such as in the frozen and uncovered remains of woolly mammoths, in the polar ice caps and in isolated caves deep underground. high priority antibiotics the world health organization (who) published a revised list in 2019 of 'critically important antimicrobials for human medicine, 6th revision' with the intent that it be used "as a reference to help formulate and prioritise risk assessment and risk management strategies for containing antimicrobial resistance due to human and non-human antimicrobial use to help preserve the effectiveness of currently available antimicrobials. it lists its highest priority critically important antimicrobials as: 3rd, 4th and 5th generation cephalosporins, glycopeptides, macrolides and ketolides, polymyxins including colistin, and quinolones including fluoroqinolones. the european medicines agency (ema) antimicrobial advice ad hoc expert group (ameg) also published an updated categorisation of different antibiotics in veterinary medicine by the antibiotic resistance risk to humans of using them alongside the need to treat disease in animals for health and welfare reasons. the categorisation specifically focuses on the situation in europe. category a ('avoid') antibiotics are designated as 'not appropriate for use in food producing animals'. category b ('restrict') products, also known as highest priority critically important antibiotics, are only to be used as a last resort. these include quinolones (such as fluoroquinolones), 3rd and 4th generation cephalosporins, and polymyxins, including colistin. a new intermediate category c ('caution') has been created for antibiotics which should be used when there is no available product in category d ('prudence') that would be clinically effective. category c includes macrolides and aminoglycosides, with the exception of spectinomycin, which remains in category d. evidence for the transfer of macrolide-resistant microorganisms from animals to humans has been scant, and most evidence shows that pathogens of concern in human populations originated in humans and are maintained there, with rare cases of transference to humans. macrolides are also extremely useful in the effective treatment of some mycoplasma species in poultry, lawsonia in pigs, respiratory tract infections in cattle and in some circumstances, lameness in sheep. summary while the human medical use of antibiotics is the main source of antibiotic resistant infections in humans, it is known that humans can acquire antibiotic resistance genes from a variety of animal sources, including farm animals, pets and wildlife. three potential mechanisms by which agricultural antibiotic use could lead to human disease have been identified as: 1 - direct infection with resistant bacteria from an animal source; 2 - breaches in the species barrier followed by sustained transmission in humans of resistant strains arising in livestock; 3 - transfer of resistance genes from agriculture into human pathogens. while there is evidence of transmission of resistance from animals to humans in all three cases, either the scale is limited or causality is hard to establish. as chang et al (2014) state: "the topic of agricultural antibiotic use is complex. as we noted ... many believe that agricultural antibiotics have become a critical threat to human health. while the concern is not unwarranted, the extent of the problem may be exaggerated. there is no evidence that agriculture is 'largely to blame' for the increase in resistant strains and we should not be distracted from finding adequate ways to ensure appropriate antibiotic use in all settings, the most important of which being clinical medicine." direct contact with animals in terms of direct infection with resistant bacteria from an animals source, studies have shown that direct contact with livestock can lead to the spread of antibiotic-resistant bacteria. the risk appears greatest in those handling or managing livestock, for example in a study where resistant bacteria were monitored in farm labourers and