Antimicrobial Feed Additives for Swine: Past, Present and Future Trends

Livestock Update, February 2004

Allen Harper, Extension Animal Scientist ­ Swine, Tidewater AREC and Mark Estienne, Swine Research Physiologist, Tidewater AREC

Background
Sub-therapeutic levels of antimicrobial feed additives have been used in swine feeds since the 1950's for improved growth rate and feed efficiency and to maintain pig performance in the presence of sub-clinical disease. The most effective use is in the diets of weanling and young growing pigs but responses are also obtained in finisher pigs and breeding swine. Over 15 years ago Zimmerman (1986) summarized the data from 239 separate experiments and reported that average improvement response to antimicrobial feed additives in starter pigs was 15% for growth rate and 6% for feed efficiency. In older growing-finishing pigs the improvement was 4% for growth rate and 2% for feed efficiency. It is believed that weanling and starter pigs are more susceptible to stress and sub-clinical disease and consequently show a greater response to growth promoting antimicrobial products. Studies have also indicated that both starter and finisher pigs have a greater response to antimicrobials under farm conditions than at swine research facilities, possibly because the disease, sanitation and housing stresses are typically greater at commercial farms than in research facilities.

The consistent effectiveness of antimicrobial feed additives has led to extensive use in the swine feeding industry. Cromwell (2001) estimated that 80 to 90% of all starter pig feeds, 70 to 80% of all grower pig feeds, 50 to 60% of all finisher pig feeds and 40 to 50% of all sow feeds are fortified with antimicrobial feed additives. There are 18 antimicrobial feed additive products currently approved by the U.S. Food and Drug Administration for use in swine diets (Table 1). General reviews on the use and effects of antimicrobial feed additives for swine are available from Cromwell (2001) and in Pork Industry Handbook fact sheet 31, Feed Additives for Swine (Parker and co-workers, 1994).

Despite their effectiveness, continued use of antimicrobial growth promoters faces a very uncertain future. In 1999, the European Union of agricultural ministers banned the use of virginiamycin, spiramycin, tylosin phosphate and zinc bacitracin (Smith, 1999). In addition, avoparcin, olaquindox and carbadox are also not allowed for use as growth promoters in Europe. In this country the U.S. Food and Drug Administration (FDA) and Centers for Disease Control (CDC) have called for an extensive reevaluation of continued use of antimicrobial feed additives (Smith, 1999, Elliott, 2001).

One concern associated with use of antimicrobial feed additives is the potential for antimicrobial residues in meat products of treated animals. For this reason certain antimicrobial feed additives have a legally required pre-slaughter withdrawal period during which time the animals must not be fed the product before shipping for slaughter (Table 2). Table 1. Antimicrobial Agents Approved for use in Swine Feeds^a

Generic Name	Classification	Example Trade Names
Apramycin	Antibiotic	Apralan
Arsanilic acid	Chemotherapeutic	Pro-Gen 20%
Bacitracin methylene disalicylate	Antibiotic	BMD
Bacitracin zinc	Antibiotic	Baciferm
Bambermycins	Antibiotic	Flavomycin, Gainpro
Carbadox	Chemotherapeutic	Mecadox
Chlortetracycline	Antibiotic	CTC, Pennchlor
Lincomycin	Antibiotic	Lincomix
Neomycin	Antibiotic	Neomix, Neo-terramycin
Oxytetracycline	Antibiotic	OXTC, Pennox
Penicillin	Antibiotic	CSP-250, CSP-500
Roxarsone	Chemotherapeutic	3-Nitro
Sulfamethazine	Chemotherapeutic	Tylan 40 Sulfa-G
Sulfathiozole	Chemotherapeutic	CSP-250, CSP-500
Tiamulin	Antibiotic	Denagard
Tilmicosin	Antibiotic	Pulmotil 90
Tylosin	Antibiotic	Tylan 40, Tylan 100
Virginiamycin	Antibiotic	Stafac

^a Source: Feed Additive Compendium, 2004.

Table 2. Antimicrobial Feed Additives Requiring a Pre-slaughter Withdrawal^a

Generic name	Example trade name	Pre-slaughter withdrawal (days)
Apramycin	Apralan	28
Carbadox	Mecadox	42
Neomycin	Neomix Ag 325	3
Oxytetracycline	Terramycin 10 - 50 grams/ton 10 mg/kg body weight	0 5
Oxytetracycline + Neomycin sulfate	Neo-Terramycin 50/50	5
Roxarsone	3-Nitro 20	5
Sulfamethazine	Tylan 40 Sulfa-G	15
Sulfathiozole	CSP-250, CSP-500	7
Tiamulin	Denagard 10 grams/ton 35 grams/ton 200 grams/ton	0 2 7
Tilmicosin	Pilmotil 18	7

^a Source: Feed Additive Compendium, 2004.

An even greater concern among regulatory agencies and consumers is the potential that regular use of antimicrobial feed additives may lead to the development of resistant microbes that may compromise the effectiveness of antibiotics in treating animal and human disease. But, there is considerable debate as to whether the use of antimicrobial feed additives will lead to a significant risk of inability to treat disease. For example, long-term studies have shown that using feed grade antimicrobials on swine farms for extended periods of time does lead to the development of resistant organisms but that the growth promoting effects of the products continue to be realized. Furthermore, within a herd in which antimicrobial use was suspended for over 13 years, significant levels of resistant microbe strains were still identified (Langlois and co-workers, 1986). Nevertheless the impetus for banning antimicrobial feed additives in food animal production is very strong. Such forces as consumer acceptance, export markets and medical community directives are likely to force loss of some, if not all antimicrobial feed additives for performance enhancement in food animals.

Can We Produce Pigs without Antimicrobial Feed Additives?
The simple (and absolutely correct) answer to this question is a definite yes. There are currently a limited but growing number of small producers that grow pigs without antimicrobial feed additives for "organic" or other specialty markets. And more conventional producers are reducing the quantity of antimicrobials being used. However, what is less apparent is what producers have to give up in terms of pig productivity and efficiency if antimicrobial feed additives are not used.

The issue has stimulated interest in alternatives to antimicrobial feed additives. Included among potential alternatives are complex mannose carbohydrates termed mannanoligosaccharides derived from the cell wall of yeasts. There is evidence that dietary inclusion of mannanoligosaccharides has immunomodulatory properties and may improve growth performance of weanling pigs (Spring and Privulescu, 1999). So-called probiotics are a second category of potential replacements for antimicrobial growth promoters. Probiotics generally refer to viable microbial cultures that are intended to increase the gastrointestinal population of beneficial microbes while competitively excluding bacteria that may depress health or growth performance (Cromwell, 2001).

At the Virginia Tech Tidewater AREC we assessed two commercially available feed additives in 5-week nursery pig trials as potential alternatives to traditional antimicrobial feed additives (Harper and Estienne, 2002). In trial 1 a mannanoligosaccharide (Bio-Mos, Alltech Incorporated) was evaluated with the antimicrobial feed additive carbadox (Mecadox, Phibro Animal Health). Treatments included: 1) a control diet with no supplemental feed additive; 2) a diet containing Bio-Mos (0.3% during wk 1 and 0.2% for wk 2-5); 3) a diet containing carbadox (50 grams/ton); and, 4) a diet containing both additives.

Results are summarized in Table 3. There were no main effects of Bio-Mos supplementation and no interaction effects of Bio-Mos and carbadox in combination (P > 0.40). The main effects of carbadox supplementation were an 8 % increase in feed consumption and a 9 % improvement in growth rate (P < 0.01).

In trial 2, a probiotic product (BioMate-2B, Chris Hansen Biosystems) consisting of Bacillus licheniformis and subtilis was assessed. Treatments included: 1) a control diet with no feed additive; 2) a diet containing Bacillus additive (0.1%); 3) a diet containing carbadox (50 grams/ton); and, 4) a diet containing both additives.

Results are presented in Table 4. For the overall 5-wk trial there was no Bacillus by carbadox interaction (P > 0.44) and no Bacillus main effect improvements in pig performance. A slight reduction in growth rate (4 %) with Bacillus supplementation was observed (P < 0.05). Main effects of carbadox were a 9 % increase in growth rate and a 4 % improvement in feed conversion efficiency (P < 0.01).

Table 3. Effects of BioMos and(or) Carbadox Addition to Nursery Pig Feeds

	Dietary treatment
Item	Control	BioMosa	Carbadoxb	BioMos + Carbadox	SEM
No. of pensc	5	5	5	5
Body Wt., kg
Initial	7.34	7.33	7.31	7.29	0.02
Week 51	22.97	23.09	24.44	24.39	0.32
Daily gain, gm/day
Weeks 1-51	446	450	489	489	9
Feed intake, gm/day
Weeks 1-51	770	769	840	826	17
Feed/gain
Weeks 1-5	1.73	1.72	1.72	1.69	0.04

^aBioMos® (Alltech, Inc., Nicholasville, KY) supplemented at 0.3% of diet during wk 1 and 0.2% of diet during wks 2-5.
^bThe carbadox source was Mecadox® (Phibro Animal Health, Fairfield, NJ) supplemented at 50 grams/ton of the diet.
^cFive replicate pens per treatment with 4 pigs per pen.
¹Main effect of carbadox, P < 0.01.

Table 4. Effects of Bacillus Probiotic and(or) Carbadox Addition to Nursery Pig Feeds

	Dietary treatment
Item	Control	Bacillusa	Carbadoxb	Bacillus + Carbadox	SEM
No. of pensc	7	7	7	7
Body Wt., kg
Initial	7.31	7.30	7.29	7.32	0.02
Week 51	24.20	23.33	25.53	24.92	0.34
Daily Gain, gm/day
Weeks 1-51,2	483	458	521	503	10
Feed intake, gm/day
Weeks 1-5	779	759	818	795	19
Feed/gain
Weeks 1-51	1.62	1.66	1.57	1.58	0.02

^aThe Bacillus source was BioPlus-2B® (Chr. Hansen Biosystems Inc., Milwaukee, WI) supplemented at 0.1% ppm of the diet.
^bThe carbadox source was Mecadox® (Phibro Animal Health, Fairfield, NJ) supplemented at 50 grams/ton of the diet.
^cSeven replicate pens per treatment with 4 pigs per pen.
¹Main effect of carbadox, P < 0.01.
²Main effect of Bacillus, P < 0.05.

In these two experiments the picture was very clear. The traditional antimicrobial feed additive carbadox (Mecadox®) was definitely effective in enhancing growth performance of nursery pigs. This was true even though the unsupplemented control pigs performed quite well. The two alternative products, however, had no positive influence on pig growth performance. A definitive conclusion about the effectiveness of alternative products like BioMos and BioMate-2B cannot be drawn from two small growth trials at one location. But, these trials do agree with the overwhelming majority of nursery pig and growing pig data that has been generated. Recently a large scale review of growth trials involving alternative products for feed additive antimicrobials was published (Turner and co-workers, 2001). The overall conclusion from this review was that in some cases probiotics and other alternative products improve performance, but not in the majority of cases. Supplementing antimicrobial additives does not always result in improved performance either. But, what can be safely stated is that traditional antimicrobial feed additives will enhance pig performance more consistently and the magnitude of the improvement will be greater than with currently available alternative products.

What Factors will be Important if Antimicrobial Feed Additives are Banned?
Overall Herd Health. Maintaining good overall herd health has always been important. But, it may become even more important if feed additive antimicrobials are not permitted. Building immunity to specific diseases in the breeding herd and transferring that immunity to pigs will be important. Vaccination programs for farm specific disease threats will be critical for the breeding herd and, when applicable, in nursing and growing pigs as well. When disease problems do occur, accurate veterinary diagnosis and appropriate treatment will be essential. On this point it is noteworthy that in some European swine herds that discontinued antimicrobial feed additive use, the incidence of post-weaning diarrhea and therapeutic (veterinary prescribed) use of some antimicrobials actually increased.

Optimal Rearing Environment and Husbandry. It is well established that pigs respond to a properly managed rearing environment with good performance and fewer disease problems. This may be even more critical in the absence of antimicrobial feed additives. Clean sanitized facilities with carefully regulated ventilation (air movement and air quality) and temperature requirements are particularly important. Appropriate pen stocking density (floor space) is also a potentially important factor. All-In, all-out management by barn or by pig room is an effective husbandry tool under any circumstance. But, the value of all-in, all-out management may be even more critical if antimicrobial feed additives are not used. Proper cleaning, disinfection and dry-down of facilities between pig groups are essential to realize the full benefits of all-in, all-out pig group management.

Feeding and Nutritional Strategies. Although probiotics and other alternative products are not as consistently effective as antimicrobials, there does appear to be some farm specific conditions under which certain products give a response. Perhaps the only way this can be determined is through on-farm trials. If no response can be demonstrated, use of the particular product cannot be economically justified.

However, two relatively low-cost products have been used that yield performance responses in weanling and nursery pigs with reasonable consistency. Specifically, high dietary levels of copper, usually in the form of copper sulfate, will produce improved growth performance in weanling and nursery pigs and high dietary levels of zinc, usually in the form of zinc oxide, will improve performance of weanling pigs. The added copper supplementation rate is typically in the range of 200 to 300 parts per million (ppm) which is substantially greater than the 5 to 15 ppm of copper provided in trace mineral supplements. For zinc the supplementation rate is 2500 to 3000 ppm, much higher than the 80 to 120 ppm typically provided by trace mineral supplements.

In the event of a ban on antimicrobial feed additives, the use of elevated copper and zinc addition to young pig diets is likely to increase. However, two important considerations are in order. First, at the recommended levels these minerals can stimulate performance. But, at dietary levels beyond 300 ppm for copper and 3000 ppm for zinc, these minerals can actually be toxic and impair health and performance of pigs. Secondly, supplementing growth promotional levels of copper or zinc in the diet will result in greater excretion of these minerals in the manure. In situations where copper and zinc accumulation in soils receiving manure is a potential problem, use of elevated dietary copper and zinc may not be feasible.

Another nutritional strategy that warrants attention is addition of spray dried plasma protein at levels of 4 to 8% of the diet for early weaned pigs. Use of this product in the phase I diet of weanling pigs has consistently resulted in improved feed intake and growth. There is some evidence that this is related to immunological properties of plasma protein products. In trials involving un-medicated diets at our unit, spray dried plasma has shown good performance responses during the initial week after weaning. However, response to this product is limited to early weaned pigs and it very expensive. Therefore its use is limited mainly to the initial post-weaning diet.

Current Considerations
In the future, regulatory action and consumer preferences may force swine producers to alter or discontinue antimicrobial feed additive use. For now there are several key points to consider as this issue continues to develop. Antimicrobial feed additive should be used with strict adherence to approved label specifications. Specific approved uses, dietary supplementation levels and minimum pre-slaughter withdrawal times should be followed precisely. In addition, good production practices at commercial feed mills and on-farm mills will be important for safe, effective use of antimicrobial additives.

Feed additives should be viewed as a performance tool that is used along with good swine herd management. They should not be considered as a substitute for proper herd health maintenance, good sanitation and effective bio-security practices.

Growth and feed efficiency responses to various antimicrobial additives do not occur in every herd or in every situation within a herd. It may be necessary to conduct a controlled on-farm performance trial to determine if a particular feed additive is providing a performance response and yielding an economic return on investment. This point is particularly true in finishing pigs, which do not show the same consistency of response to feed additives as starter pigs.

The concern about antimicrobial additives has stimulated a renewed interest in potential alternatives. Probiotics , oligosaccharides, acidifiers and high levels of copper sulfate and zinc oxide will potentially see increased interest if use of antimicrobials is banned or reduced. However, the same principles of safe, economical and effective use of feed additives will apply to these products as with antimicrobials.

References
Anonymous. 2004. Feed Additive Compendium, Miller Publishing Co., Minnetonka, MN.

Cromwell, G. L. 2001. Antimicrobial and promicrobial agents. Page 401 in Swine Nutrition, 2nd edition. A. Lewis and L. Southern, ed. CRC Press, Boca Raton, FL.

Elliott, I. 2001. EU plans phase-out of antibiotic use. Feedstuffs 74(13):1.

Harper, A.F., and M.J. Estienne. 2002. Efficacy of three potential alternatives to antimicrobial feed additives for weanling pigs. Prof. Animal Scientist 18: 343-350.

Langlois, B.E., K.A. Dawson, G.L. Cromwell, and T.S. Stahly. 1986. Antibiotic resistance in pigs following a 13 year ban. J. Anim. Sci. 62(suppl. 3):18.

Parker, G., G. Cromwell, V. Hays, and J. McKean. 1994. Feed additives for swine. Pork Industry Handbook Fact Sheet 31, Purdue University Cooperative Extension Service, West Lafayette, IN.

Smith, R. 1999. Antibiotic bans, regulations may stop development of drugs. Feedstuffs, March 29, 1999, p. 5.

Spring, P., and M. Privulescu. 1999. Mannanoligosaccharide: its logical role as a natural feed additive for piglets. In: Biotechnology in the Feed Industry, Proc. 14th Annu. Symp. T.P. Lyons and K. A. Jaques (Eds.) p. 553. Nottingham University Press, Nottingham, UK.

Turner, J.L., S.S. Dritz, and J.E. Minton. 2001. Alternatives to conventional antimicrobials in swine diets. Prof. Animal Scientist. 17:217-226.

Zimmerman, D.R. 1986. Role of subtherapeutic antimicrobials in pig production. J. Anim. Sci. 62(Suppl. 3):6.

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