Maintenance of healthy animals requires prevention of infection by pathogenic organisms. In addition, specific alteration of a host’s microflora may have beneficial effects on animal production by alteration of ruminal flora, resulting in changes in the proportions of volatile fatty acids produced during ruminal digestion. Thus, antimicrobial compounds may improve production efficiency of healthy animals fed optimal nutritional regimens.
Production-enhancing antimicrobial compounds can be classified as ionophore or nonionophore antimicrobials. This distinction is important, because ionophores have no use in human medicine and do not have any link or possible effect on antimicrobial resistance to therapeutic antimicrobials in either humans or food animals.
Antimicrobial compounds are administered in the feed at low doses relative to high doses required for therapeutic effects. Feed additives can be administered once the rumen is functioning, although some antimicrobial compounds can be fed to calves before this point. Many antimicrobials have multiple applications, with growth promotion not often listed as the sole indication. When the FDA released the Guidance for Industry #213 in 2013, the intention was to encourage pharmaceutical companies to voluntarily remove growth promotion claims from previously approved nonionophore feed-grade antimicrobials. Thus, the observed influence of nonionophore feed grade antimicrobials on animal growth performance responses should not be used as a marketing claim, even though treating clinical and subclinical illness can improve growth rate over non-treated animals.
Antimicrobial growth promotants commonly used in production animals are detailed in Antibacterial Growth Promotants in Production Animals. Antimicrobials are used in male and female animals without adverse effects on ovarian and testicular development or function because they are poorly absorbed. Unlike anabolic steroids, they do not affect carcass composition. Some implants also contain an antimicrobial, such as oxytetracycline or tylosin tartrate, to provide a local antibacterial effect at the implant site.
Ionophore antimicrobials
Ionophores (eg, monensin,lasalocid, and laidlomycin propionate) modify the movement of monovalent (sodium and potassium) and divalent (calcium) ions across biological membranes, modify the rumen microflora, decrease acetate and methane production, increase propionate, may improve nitrogen utilization, and can increase dry-matter digestibility in ruminants. Their main effect is to increase feed efficiency; however, they may also improve growth rates of ruminants on high-roughage diets. Administration of monensin to cattle results in 2%–10% improvement in liveweight gain (in animals on a high-roughage diet), 3%–7% increase in feed conversion efficiency, and up to a 6% decrease in food consumption. Initially, monensin was used only as a feed additive for ruminants fed in confinement; however, its use has been extended to grazing animals as well. Other ionophores generally have similar effects. Doses range from 4 to 40 ppm in the diet. Ionophores are absorbed from the gut, rapidly metabolized by the liver, and re-enter the gut from bile. Some ionophores also have a therapeutic use (eg, monensin sodium for prevention of coccidiosis in ruminants and poultry).
Although ionophore antimicrobials are used for prevention of coccidiosis in ruminants and poultry, ionophores are not used in human medicine, and there are no medically important analogues of the ionophores used in human medicine. Therefore, there is no obvious relationship between ionophore use in production animals and the concern regarding resistance of bacterial pathogens to antimicrobial compounds important in medicine for humans.
Nonionophore antimicrobials
These compounds are used to selectively modify microbial populations within animals to improve production efficiency and to maintain health by combating low-level infections, particularly in intensive production systems. Phosphoglycolipid antimicrobials (eg, flavophospholipol) alter ruminal flora by inhibiting the action of some gram-positive gut microorganisms and peptoglycan formation, yielding similar production responses to those produced by ionophores. In addition, flavophospholipol has been shown to influence the hindgut microflora populations in production animals, resulting in competitive exclusion of some harmful pathogens such as Escherichia coli and various species of Salmonella. A less understood effect of flavophospholipol is the reduction in plasmid transfer of antimicrobial resistance. Given the seemingly contradictory and highly charged interests of desire for a generalized reduction in the use of antimicrobials for production animals and the potential use of a specific antimicrobial for reducing antimicrobial resistance, this potentially volatile topic has not been comprehensively assessed to date.
The means by which specific compounds exert their antimicrobial effect differ. Antimicrobials may have a nitrogen-sparing effect, thereby increasing the availability of amino acids to the animal to support growth of economically relevant tissue depots such as skeletal muscle.
Some feeds used for broiler and pig production in certain countries contain antimicrobial growth promoters. However, recently, many of these products have been discontinued for growth promoting purposes and are only used to treat and prevent disease. These compounds can also be administered to calves, yearlings, and finishing cattle either in milk replacer or in supplementary concentrates fed to cattle. Antimicrobial compounds, in general, increase growth rate by 2%–10% and feed conversion efficiency by 3%–9%, with minimal influence on dry-matter intake. Their effects are greater in young animals, and production responses are decreased when production conditions are optimized (good housing, optimal health, and adequate hygiene). They have minimal effects on carcass composition other than that because of improved growth rate, which might result in lighter harvest weights due to the fact that more rapid gain results in attainment of chemical maturity earlier in life.
The development of microbial resistance to antimicrobials in treated animals, which can then be transmitted to humans, is an important concern regarding the widespread use of antimicrobial feed additives in food animal production. There is circumstantial evidence that use of subtherapeutic doses of antimicrobials creates selective pressure for the emergence of antimicrobial resistance, which may be transmitted to the consumer from food or via contact with treated animals or animal manure. A ban on the use of antimicrobials as feed additives decreased drug-resistant bacteria in a Danish study. Although overall mortality rates of chickens were not affected, more feed was consumed per kg of weight, which results in poorer feed conversion efficiency. Therapeutic use of antimicrobials was increased; however, the total volume of antimicrobial use was significantly decreased.
The EU has banned bacitracin, carbodox, olaquindox, tylosin, virginiamycin, avilamycin, flavophospholipol, lasalocid sodium, monensin sodium, and salinomycin as of 2009, even though some of these compounds are not medically important to humans and pose little risk to development of antimicrobial resistance in humans. There has been no reported evidence of any reduction in antimicrobial resistance in human bacterial pathogens as a result of the EU ban. The most important and concerning cases of antimicrobial resistance in human medicine, namely methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE), Streptococcus pneumoniae, and others, are not food-borne pathogens and are not found in food or companion animals; the drugs of interest are not used and were not used in human medicine before the ban in production animals. In the US, the passage of the Veterinary Feed Directive has been implemented to decrease the unwarranted use of antimicrobials in US food production systems and has been deemed necessary to provide judicious use of antimicrobials in US animal food production.
