The Effects on Human Health of Subtherapeutic Use of Antimicrobials in Animal Feeds (1980) / Chapter Skim
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Appendix K: Advisory Panel Report on Antibiotics in Animal Feeds
Appendix K: Advisory Panel Report on Antibiotics in Animal Feeds
Pages 317-376
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APPENDIX K ANT IBIOT ICS IN ANIMAL FEEDS Committee on Animal Health and the Committee on Animal Nutrition Board on Agriculture and Renewable Resources National Research Council 317
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CONTENTS EXE CUT IVE SUMMARY CHAPTER 1 INTRODUCT ION ClIAPTER 2 SUBTHERAPEUTIC USE OF ANTIBIOTIC S Animal Management Swine Poultry Cattle and Sheep Amount Used and Feed Preparation Swine Poultry Ruminants Effects of Restrictions Swine Poultry Ruminants Economic Effects of a Ban on the Use of Antibiotics Future Changes in Antibiotic Use Alternatives Environmental and Management Changes Selection for Genetic Resistance in Natural Immunity Development of Vaccines Adaptation of Minimal Disease Programs Development of New Antibiotics CHAPTER 3 EFFICACY OF ANTIBIOTICS IN ANIMAL FEEDS Swine Poultry Cattle and Sheep CHAPTER 4 RESTRICTIONS ON ANTIBIOTICS IN EUROPE Background Antibiotic Use Performance Resistance CHAPTER 5 EFFECTS ON ANIMAL DISEASE OF SUBTHERAPEUTIC USE OF ANTIBIOTICS 319 321 325 328 328 328 331 332 332 332 333 336 338 338 338 339 339 341 343 344 345 345 345 346 347 347 350 350 354 354 355 357 357 360
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320 CHAPTER 6 THERAPEUT IC USE OF ANT IBIOT ICS Background Control and Regulation Epidemiological Considerations CHAPTER 7 VOIDS IN KNOWLEDGE AND SUGGESTED RESEARCH Effect of Tetracycline Feeding on Animal Therapy Poult ry and Swine Cattle Relation of Antibiotic Feeding to Human Health Mechanisms of Action of Antibiotics in Growth Promot ion REFERENCES 363 363 366 366 368 368 368 369 370 370 372
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From page 321... ...
. supplements and premixes that are processed and sold by Feedlot systems for beef cattle and sheep would not change if low-level antibiotic feedings were not permitted, but it is likely that disease problems and therapeutic use of antibiotics would increase.
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The British have monitored microbial resistance to antibiotics and have conducted some basic and applied research concerning this aspect. Although the use of antibiotics in the United Kingdom has been restricted as a result of the Report of the Joint Committee on the Use of Antibiotics in Animal Husbandary and Veterinary Medicine (referred to in this report as the Swann Report; Swann et al.
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Yet, it is difficult - ~ - ~ ran he Tori hi .~n~r; fist lv to cite human health problems that ~ rid to meat animals fed antibiotics or that can be associated with contact with animals fed low levels of antibiotics. There have been incidents of salmoneDlosis in humans involving antibioticresistant strains of animal origin but there is no evidence of any relation to low-level antibiotic feeding.
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2. The Relationship of Antibiotic Feeding to Human Health-Although these studies are very complex and time-consuming, it is important that some effort be started in this direction.
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has proposed a ban on certain antibiotics at subtherapeutic levels in feed because of the potential for compromising the health of humans. A large segment of the regulated industry, including fanners and ranchers, has contended that in nearly 30 years of use, antibiotics at subtherapeutic levels in animals have not compro mised human or animal health or influenced the therapy of human disease.
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4. What do the data from European countries show with respect to animal health and nutrition where antibiotics have been restricted?
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(Chapters 5, 6) BARR asked its Committees on Animal Nutrition and Animal Health to set up a panel of their members and outside consultants to address these questions.
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The swine industry differs from the broiler industry, however, since nearly all the production is by private producers rather than by industrial entities. An appreciation of the change to intensive swine production is evident in Table 2.1.
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329 TABLE 2.1 Number of Farms with Pigs in the United States and Iowa and Total U.S. Production Number of Farms Number of Farms Total U.S.
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330 TABLE 2.2 Number of Large-Volume Producers and Size of Operationa Number of Number of Operations Operations Producing Average Producing Average 2,500 to 4,999 Size of 5,000 Head Size of Year Head/Year Operation or More/Year Operation 1975 1,567 2,418a 1,168 7,053 1978 1,661 3,196 1,340 10,192 a A producer was included in this category if production was 2,500 head or more in any year included in the survey. SOURCE: Stemme et al.
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It is likely that the use of antimicrobial agents has facilitated the development of the concentrated operations. Poultry As part of the effort to produce poultry meat and eggs as economically as possible, it is common practice in the United States to maintain broilers, turkeys, and laying hens in large flocks in one location.
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An estimated 50 to 60 percent of feedlot cattle are fed low-level antibiotics during the feeding period and a total of 40 percent of the total beef supply has been fed low-level antibiotics (USDA 1979b)
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Most of the feed-manufacturer tonnage is sold as supplements (protein, minerals, vitamins, and feed additives) to be further mixed or diluted with grain for feeding as a complete balanced diet by the swine producer.
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FIGURE 2.1 Market structure of formula feed industry.
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Since response to antibiotics fed to the lactating sow are not consistent, no general recommendation is made for their inclusion by experiment stations.
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Most of the feed mixed for poultry production in the United States is made by large integrated companies and in large feed mills where careful control of the inclusion of the drugs and other feed ingredients is maintained on inventories. The feed manufacturers, in using drugs in poultry rations, must follow regulations of the FDA and be inspected periodically by this agency and state feed control officials.
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2. For growth promotion and improvement of feed efficiency, the recommended levels of feeding are 70 to 80 mg/day (Anonymous 1979c)
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for growth stimulation would have little effect since they are not used now to any extent for this purpose. The elimination of the use of higher levels of tetracyclines, however, would create problems in the control of bacterial diseases in young chickens and turkeys and in maintaining optimum performance of laying hens.
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Disease problems and carcass condemnations would increase, and therapeutic use of antibiotics would increase. ECONOMIC EFFECTS OF A BAN ON THE USE OF ANTIBIOTICS Potential economic effects of a ban on antibiotic feed additives for 1973 livestock output, price, and cost conditions were examined by Gilliam and Martin (1975~.
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340 TABLE 2.4 Summary of Changes in Net Farm Income and USDA Food Market Basket from Banning All Subtherapeutic Use of Animal Drugs, First and Fifth Year after Ban First Year F if th Year Farm Income Moderate Drug Efficacy Change in billion dollar Change in percent High Drug Efficacy Change in billion dollars Change in percent Food Market Basket:a Base (dollars) Moderate Drug Efficacy Change in dollars Percent change from base High Drug Efficacy Change in dollars Percent change from base 5 + 1.2 + 4.7 + 2.8 +10.8 2, 132 +32.0 + 1.5 +99.0 + 4.6 - 0.5 - 2.1 0.9 - 3.81 2,530 + 5.0 + 0.2 +16.0 + 0.7 aThe market basket is the average quantities of domestic farm-origin foods purchased annually in retail food stores per urban household.
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Such control is particularly important for young susceptible animals during the rapid growth phase. The main methods of controlling infectious disease are: ~ 1.
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342 TABLE 2.5 Effects of Banning Selected Antibiotic and Drug Feed Additives on Annual Consumer Expenditures for Meat Estimated Annual Consumer Costs Option Per Capita ($) Nationally (billion $)
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ALTERNATIVES Resistance characteristics similar to those from tetracyclines and penicillin evolve when most other approved feed-additive antibiotics for swine are fed (Fagerberg and Quarles 1979~. Certain sulfa drugs may be eliminated as feed additives because of residue problems, and carbadox and furazolidone are possible carcinogens.
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development of new feed additives that do not promote bacterial resistance relevant to human and animal health. Environmental and Management Changes Reducing the production intensity of facilities would reduce the enteric problems commonly encountered in farrowing and baby pig facilities, and would reduce respiratory problems in cattle feedlots.
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Adaptation of Minimal Disease Programs Swine herds free of respiratory problems can be maintained in that condition for some reasonable period of time. This state can be attained by hysterectomizing pregnant sows and raising the young pigs in isolation in the first generation.
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The goal of research should be the development of such compounds that avoid the characteristics that are thought to pose health hazards of men and animals as recognized by today1s standards.
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The liveweight gain response of young pigs fed tetracyclines during the 1967 to 1977 period was greater than during the 1950 to 1956 period. Feed efficiency response was not as great, but the initial weights of the experimental pigs used in the 1967 to 1977 comparison was considerably greater (7 vs.
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Hi ~ ^ a, ~A, 3 Cal ~· ~ _ _ _ _ ~_ _ _ CS, ~oo m.
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349 TABLE 3.2 Effect of Antibiotics on Farrowing Rate Number of Farrowing Rate (%) Drug Sows Control Treated Chlortetracycline -179 62 79 Chlortetracycline 198 J4 86 Aureo SP-250 96 81 96 Aureo SP-250 126 53 56 Aureo SP-250 79 30 36 Tylosin 192 75 77 Tylosin 143 81 84 Tylosin-Sulfamethazine 197 70 83 Furazolidone 87 63 93 Chlortetracycline 249 67 75 Chlortetracycline 239 71 72 Aureo SP-250 184 61 70 Chlortetracycline 101 90 94 SOURCE: V
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CATTLE AND SHEEP Feedlot cattle rate of gain and feed efficiency responses to antibiotics are both improved about 5 percent (Table 3.4~. The tetracyclines have been the most widely used antibiotics in the beef cattle industry.
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352 TABLE 3.4 Cat tie Feeding Trials with Chlortetracycline Number of Comparisons Percent Trials Control Antibiotic Improvement Source Dailv Gain ~ lbs )
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TABLE 3.5 Calf Feeding Trials with Chlortetracycline a Number of Comparison Percent Trials Control Antibiotic Improvement _ Daily Gain (lbs)
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cold and Salmonella species became established in animals that had received antibiotics as feed additives or therapeutically. However, there were no substantial indications that bacterial resistance had interfered with therapy by a particular antibiotic.
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The 25 percent used for nonmedical purposes was divided 70:30 for veterinary and growth promotion, respectively. There is little indication that overall sales of antibiotics for veterinary use has decreased as a result of the Swann Report (Lipton 1977a)
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Reprinted by permission of Journal of Animal Science 46:1425.
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Large differences have been found in drug resistance of E cold between animals fed and those not fed antibiotics.
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Richmond and Linton (1980) stated overall, therefore, it seems as though we must look to the medical, as opposed to the veterinary, use of tetracycline as the main selective pressure for the high incidence of tetracycline-resistant organisms in the human population, and the source of such organisms in human beings not receiving antibiotics is more likely to lie in human beings who are being treated than in the farm animal population.
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The Scientific Committee for Animal Nutrition was set up by the Commission of the European Communities to provide informed opinions on matters pertaining to animal nutrition and effects of production methods on food quality and the environment. A series of reports was prepared by the Scientific Committee for Animal Nutrition (1978)
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During this same period, the poultry, swine, and beef cattle industries were able to develop large, highly intense production units by the use of antibiotics to control disease problems or to increase performance. Subtherapeutic levels of antibiotics have been def ined by the FDA as lower than the therapeutic levels needed to cure disease.
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Epidemiological studies show that foods of animal origin are frequently involved. Salmonellosis in humans involving antibiotic-resistant strains of bovine origin has occurred (Anderson 1968, Threlfall et al.
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More recently, Hjerpe (1976) reported a decline in response to tetracycline therapy by pneumonic cattle simultaneous with a rise in prevalence of tetracycline, penicillin, and sulfonamide-resistant strains of Pasteurella species after feeding of subtherapeutic levels (100 g/ton)
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From page 363... ...
These studies clearly revealed that antibiotic drugs were the most frequently used agents in the treatment of animal disease. The studies involved the sampling of 5 percent of the clinical cases that were presented to the Veterinary Teaching Hospitals, including the out-patient and in-patient Large and Small Animal Hospitals and a rural outlying food-animal practice.
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In terms of efficacy and safety, there can be little doubt that the antibiotic drugs are essential therapeutic agents in the diseases of domestic animals. The widespread usage of veterinary services in the livestock industry points to a very real economic gain to the producer when veterinary services are utilized.
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Lack of susceptibility or resistance to standard concentrations of various antibiotic drugs is encountered to a varied degree with all drugs, including those that have not been used at all, or used only to a minimal extent for low-level antibiotic feeding (i.e., cephalosporins, chloramphenicol, gentamicin, kanamycin)
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CONTROL AND REGULAT ION Control and regulation of the therapeutic use of antibiotic drugs is under the purview of the FDA, particularly the Bureau of Veterinary Medicine and the Bureau of Foods. Control is exercised through the mechanism of the New Animal Drug Application (NADA)
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367 feeding, therapeutic use of antibiotics in domestic animals (including companion and pet animals) , or therapeutic or prophylactic use of antibiotic drugs in human beings.
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if the feeding of tetracyclines and penicillin compromise animal therapy, (b) the relation of antibiotic feeding to human health, and (c)
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To avoid the problem of possible development of immunity, animals unexposed to the organism should also be inoculated with the dose to cause a severe infection, and the effectiveness of antibiotic therapy in these animals should also be investigated. Careful laboratory work to monitor development of antibiotic-resistant organisms in the animals and immunity development would be needed.
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In view of known factors that influence rate and efficiency of gain, antibiotic action affecting each measure of performance should prove to be, at least in some respects, different. The different chemical nature, adsorbability, and bacterial spectrum of growth promoting antibiotics suggest that the mode of action in growth promotion cannot be the same for all of the antibiotics that have proven efficacious.
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Experiments designed to uncover mechanisms related to the growth-promo/ant effect might provide a means of exploiting these mechanisms other than by the use of feeding levels of antibacterial compounds.
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Feed additives in beef cattle rations. Animal Science Leaflet, AH 805.
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(1978) Economic aspects of drug and chemical feed additives.
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Evaluation of weight gain and feed efficiency promoting efficacy of tylosin and tylosin-sulfamethazine in swine during the years 1959-1970. Feedstuffs 43~35~:23.
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(1977a) Antibiotic resistance in bacteria and associated problems in farm animals before and after the 1969 Swann Report.
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(1968) Antimicrobial feed additives for swine.
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