Antimicrobial Feed Additives

Ionophores (eg, monensin and lasalocid) modify the movement of monovalent (sodium and potassium) and divalent (calcium) ions across biologic 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, but 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, but its use has been extended to grazing animals. Other ionophores generally have similar effects. Doses range from 6–40 ppm in the diet. Ionophores are absorbed from the gut, rapidly metabolized by the liver, and reenter the gut from bile. Some ionophores also have a therapeutic use (eg, for prevention of coccidiosis in ruminants and poultry).

Although ionophore antibiotics 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 livestock production and the concern regarding resistance of bacterial pathogens to antimicrobial compounds important in human medicine.

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 systems. Phosphoglycolipid antibiotics (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, 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 antibiotics for livestock production and the potential use of a specific antibiotic for reducing antimicrobial resistance, this potentially volatile topic has not been comprehensively assessed.

The means by which specific compounds exert their antimicrobial effect differ. Antibiotics may have a nitrogen-sparing effect, thereby increasing the availability of amino acids to the animal.

Most feeds for broiler and pig production in some countries contain antimicrobial growth promoters. These compounds can also be administered to calves, yearlings, and finishing cattle either in milk replacer or in supplementary concentrates. Antibiotic compounds, in general, increase growth rate by 2%–10% and feed conversion efficiency by 3%–9%. Their effects are greater in young animals, and production responses are reduced when production conditions are optimized (good housing, optimal health, and hygiene). They have minimal effects on carcass composition other than that because of improved growth rate.

The development of microbial resistance to antibiotics in treated animals, which can then be spread to people, is an important concern regarding the widespread use of antimicrobial feed additives in food 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 through contact with treated animals or animal manure. A ban on the use of antibiotics 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. Therapeutic use of antibiotics was increased, but the total volume of antibiotic use was significantly decreased. The EU has banned bacitracin, carbodox, olaquindox, tylosin, virginiamycin, avilamycin, flavophospholipol, lasalocid sodium, monensin sodium, and salinomycin as of 2009. There has been no reported evidence of any reduction in antimicrobial resistance in human bacterial pathogens as a result of the EU ban. This is understandable given that 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, are not found in food or companion animals, and the drugs of interest are not used and were not used before the ban in livestock. The issue of antimicrobial resistance is critical for the immediate and long-term future of human medicine; however, the complexity of the issue and the difficulty with which it must be assessed ensure that clear answers are not imminent and the debate over the most appropriate path forward in the USA and abroad will continue.