Carbadox

Efficacy of Three Potential

Alternatives to Antimicrobial Feed

Additives for Weanling Pigs1

Abstract

Three 5-wk growth trials involving 288 weanling pigs were conducted to assess the efficacy of three freed additives as alternatives to antimicrobial feed additives. In Trial 1, a mannanoligosaccharide (MOS) source was evaluated with the antimicrobial feed additive carbadox. Treatments included 1) a control diet, 2) a diet containing MOS (0.3% during wk 1 and 0.2% for wk 2 through 5), 3) a diet containing carbadox (55 ppm), and 4) a diet containing both additives. For the 5-- wk trial, ADG was 446, 450, 489, and 489 g, and ADFI was 770, 769, 840, and 826 g for Treatments 1 through 4, respectively. No effects of MOS supple-- mentation and no interaction effects of MOS and carbadox were observed (P>0.40). Dietary addition of carbadox resulted in an 8% increase in feed consumption and a 9% improvement in growth rate (P

818, and 795 for Treatments 1 through 4, respectively. Overall there was no Bacillus x carbadox interaction (P>0.40). A slight reduction in growth rate with Bacillus supplementation was observed (P

(Key Words: Pigs, Feed Additive, Growth Performance.)

Introduction

Antimicrobial feed additives are used in swine production for growth promotion and maintenance of growth in the presence of subclinical disease. These additives are especially effective in weanling and starter pigs with improvements in growth rate of up to 16% and improvements in feed efficiency of up to 6% (2). The USDA National Animal Health Monitoring System (14) reported that 82% of U.S. swine farm sites with nursery pigs used antimicrobials in the feed for growth promotion or disease prevention. Despite their effectiveness, continued use of antimicrobial growth promoters faces an uncertain future. In 1999, the European Union of agricultural ministers banned the use of virginiamycin, spiramycin, tylosin phosphate, and zinc bacitracin (20). Further bans have been proposed in the European Union, and 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 (6, 20). Of particular concern is the potential for the development of resistant microbes that may compromise the effectiveness of antibiotics when treating human or animal diseases. These concerns have led to a renewed interest in alternatives to traditional antimicrobial growth promoters. Included among potential alternatives are complex mannose carbohydrates termed mannanoligosaccharides (MOS) derived from the cell wall of yeasts. There is evidence that dietary inclusion of MOS has immunomodulatory properties and may improve growth performance of weanling pigs (21). 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 nutritional performance (2). Another potential growth-promoting feed additive may be found in the form of biopolymers of amino acids such as aspartate, which have been shown to enhance nutrient uptake in agronomic plants (12). The N-methyl form of aspartate has been shown to improve feed efficiency and leanness in broiler chickens (10). The objective of this series of three experiments was to determine the growth performance effects of three potential alternatives to traditional antimicrobial growth promoters in the diets of weanling pigs.

Materials and Methods

General. Three 5-wk growth trials involving a total of 288 crossbred weanling pigs were conducted. All trials were conducted at the Virginia Tech Tidewater Agricultural Research and Extension Center swine unit in Suffolk, Virginia. At weaning, pigs were weighed and randomly allotted to dietary treatments from outcome groups based on litter of origin, BW, and sex. A clean, disinfected nursery room with supplemental heat and a negative pressure ventilation system was used to house the pigs during each trial. Pens were equipped with plastic-coated woven wire flooring, a nipple drinker, and a standard nursery feeder. Four pigs were housed in each pen with 0.67 m^sup 2^ of floor space provided per pig. Care and welfare of the pigs was in accordance with published guidelines (9).

Feed and water were available ad libitum, and special care was taken to ensure that feed freshness and proper feeder adjustment were maintained. Each experimental diet was prepared from common basal diets (Table 1) that had been formulated to meet or exceed pig nutritional requirement estimates published by the NRC (15). For Trials 1 and 2, the test products were pre-mixed with a measured portion of ground corn that had been excluded from the basal diet formulation and then thoroughly mixed with the appropriate amount of basal diet in a vertical screw mixer. The proper amount of ground corn was added back to the basal diet to prepare the negative control diets. In Trial 3, the feed additive was added in liquid form. Test diets in Trial 3 were also prepared from the common basal diet. The appropriate quantity of test product was weighed in a clean plastic bottle and brought to a total volume of 1 L with distilled water. This solution was then gradually added to the appropriate quantity of basal diet while the diet was mixing in a horizontal ribbon mixer. For the control diet, 1 L distilled water was added to the appropriate quantity of basal diet during the mixing process. Diet complexity and nutrient density were adjusted in three phases during each trial (Table 1). Formulation 1 was fed during wk 1, Formulation 2 was fed for wk 2 and 3, and Formulation 3 was fed for wk 4 and 5. Pen feed consumption and individual pig BW were measured and recorded weekly.

Trial 1. Eighty crossbred weanling pigs (Yorkshire x Landrace and Yorkshire x Landrace x Hampshire), 18 to 24 d of age, were used to evaluate the efficacy of dietary addition of a commercial feed additive consisting of brewers dried yeast and Saccharomyces cerevisiae fermentation solubles as a source of MOS (BioMos(TM); Alltech, Inc., Nicholasville, KY). This additive was assessed singly and in combination with the antibiotic carbadox (Mecadox(TM); Phibro Animal Health, Fairfield, NJ). A 2 x 2 factorial arrangement was used to provide four dietary treatments with five replicate pens per treatment. Dietary treatments included 1) a control diet with no supplemental feed additive, 2) a diet containing MOS (0.3% during wk 1 and 0.2% for wk 2 through 5), 3) a diet containing carbadox (55 ppm), and 4) a diet containing both additives at the indicated inclusion rates.

Trial 2. One hundred twelve crossbred (Yorkshire x Landrace) weanling pigs ranging in age from 19 to 23 d were used to assess the efficacy of dietary inclusion of a commercial probiotic consisting of dried cultures of Bacillus licheniformis and Bacillus subtilis (Bacillus) (BioPlus-- 2B(TM); Chr. Hansen Biosystems, Inc., Milwaukee, WI). The estimated number of Bacillus sp. cfu indicated by the manufacturer was 1,245 billion/kg. As in Trial 1, the additive was fed alone and in combination with the antibiotic carbadox using a 2 x 2 factorial arrangement of treatments. There were seven replicate pens of pigs per dietary treatment; these included: 1) a control diet with no feed additive, 2) a diet containing the Bacillus additive at 0.1%, 3) a diet containing carbadox at 55 ppm, and 4) a diet containing both additives at the indicated inclusion rates.

Trial 3. Ninety-six crossbred weanling pigs (Yorkshire x Landrace and Yorkshire x Landrace x Hampshire), 17 to 27 d of age, were used to evaluate multiple doses of a commercial polyaspartate biopolymer production (PAB) (DXL-590TM; Donlar Life Sciences, Bedford Park, IL) as a potential growth promoter for weanling pigs. The reported PAB concentration in the commercial liquid preparation was 40% by volume. Treatments included 1) a control diet with no supplemental PAB, 2) a diet with 100 ppm added PAB, 3) a diet with 200 ppm added PAB, and 4) a diet with 400 ppm added PAB; there were six replicate pens per treatment.

Fecal Firmness Scores. At the conclusion of each week, a visual appraisal of fecal firmness within each pen was conducted. The purpose was to determine possible treatment effects on fecal consistency or occurrence of diarrhea. Pen fecal firmness data were recorded based on a five-point scale. A score of 1 indicated exceptionally firm fecal material, and a score of 5 indicated very loose, watery feces. The same observer performed the stool consistency scores each week between 0800 and 0930 h.

Statistical Analysis. All data were subjected to analysis of variance using the general linear models procedure of SAS (19). In all trials, dependent performance variables included final BW, ADG, ADFI, feed:gain, and fecal firmness score. In all cases, the pen served as the experimental unit.

In Trial 1, the model tested the effects of replication, MOS addition, carbadox addition, and the interaction of the two additives. For Trial 2, the model tested effects of replication, Bacillus probiotic addition, carbadox addition, and the interaction of the two additives. In Trial 3, the model included the effects of replication and PAB addition level. Orthogonal contrasts for unequally spaced PAB levels were used to assess linear and quadratic effects.

Results and Discussion

Trial 1. Overall, the pigs performed well and completed the 5-wk trial in apparent good health. Observations for fecal firmness scores revealed no evidence of diarrhea, and there were no dietary treatment effects on fecal firmness score for any individual week (data not shown) or for mean fecal firmness scores for the overall trial (Table 2; P>0.30).

Inclusion of MOS in the diet at a level of 0.3% during wk 1 and 0.2% thereafter did not result in any main effect on growth rate, daily feed intake, or feed conversion efficiency at any period during the trial or over the total 5-wk period (Table 2; P>0.50). Throughout the course of the trial, performance of the MOS-- supplemented pigs was similar to the un-supplemented controls. Furthermore, there were no observed interactive effects of the MOS treatment and carbadox treatment (P>0.40).

Spring and Privulescu (21) described mechanisms whereby MOS, a mannose derivative isolated from yeast cell wall, may enhance health and performance of young pigs. These mechanisms center on preferential binding of potentially harmful enteric bacteria to MOS in the gut and direct enhancement of pig immune function. Several reports of trials using the same MOS source as the present experiment have indicated improved growth rate (3, 18) and feed efficiency (4, 18) during a post-weaning period of 5 to 6 wk. However, there have been circumstances under which pig performance response to MOS supplementation was inconsistent. For example, Dvorak and Jacques (5) reported some improvement in feed intake in MOS-- supplemented weanling pigs, but an antibacterial treatment (carbadox) resulted in more profound responses in growth rate. In a study involving trials in two commercial swine nursery sites and one university farm nursery site, only at the university site was a significant improvement in growth rate and feed conversion observed (18).

Pettigrew (16) has conducted a review of 13 weanling pig trials investigating MOS that were reported principally as scientific abstracts or research reports. Because growth responses were numerically small in most of these trials, the number exhibiting any statistically significant performance improvements was small (5 of 13). However, in most of these trials, performance numerically favored MOS-supplemented pigs, with an average improvement in growth rate of 4.4%. This magnitude of response is considerably less than the potential 16% growth rate response of weanling pigs to subtherapeutic levels of antimicrobial feed additives indicated by the current NRC (15).

In contrast to the response to MOS, pigs fed diets containing carbadox (55 ppm) consumed, on average, 8% more feed and grew 9% faster over the S-wk trial (Table 2). These main effect responses were significant by the first 3 wk of the trial (P

Carbadox is an antibacterial feed additive that was first approved for use in the U.S. in 1975. Current labe approvals include improved rate of gain and feed efficiency in growing swine at dietary levels of 11 to 27.5 ppm and improved rate of gain, improved feed efficiency, and control of swine dysentery and bacterial enteritis at a dietary level of 55 ppm (1). Carbadox was first demonstrated to promote growth in young pigs in 1969 (22) and has consistently yielded positive growth responses in starter pigs in subsequent reported experiments (11, 17, 24). The consistent growth response with carbadox is a likely contributing factor in the substantial usage of the drug in commercial swine production. A recent USDA survey (14) indicated that 22.890 of commercial farms with nursery pigs utilized carbadox as a feed additive, which ranked third behind use of chlortetracycline (30% of sites) and tylosin (23.2% of sites) as feed additives for nursery pigs.

Trial 2. Overall, the pigs performed well throughout the 5-wk trial. One pig on the combined Bacillus and carbadox treatment was in apparent poor health, grew at an exceptionally slow rate (40% slower than other pigs in the pen) and was removed from the study. Observations for fecal firmness scores revealed no evidence of diarrhea, and there were no dietary treatment effects on fecal firmness score for any individual week or for mean fecal firmness scores for the overall trial (Table 3; P>0.22).

During the 1st wk post-weaning, an interaction was observed between the Bacillus probiotic and carbadox (Table 3). Rate of gain, feed intake, and BW at the end of wk 1 were greater in pigs fed the additives in combination, but tended to be less than controls when either additive was fed individually (interaction, P

Supplementing the Bacillus probiotic did not result in any positive main effect responses in growth rate, feed intake, or feed efficiency during or throughout the 5-wk trial (Table 3). An unexpected observation for which we have no clear explanation was a significant (P

Dietary addition of carbadox resulted in positive main effects on growth rate and pig BW by the end of wk 3 and for the overall trial (Table 3; P

Trial 3. In general, the pigs appeared healthy and performed well throughout the trial. One pig that received the 400 ppm PAB diet was injured fighting and was removed from the study. Two other pigs, one receiving the control diet and the other receiving the 400 ppm PAB diet, developed swollen rear leg joints and were removed from the trial. Veterinary necropsy of these two pigs was inconclusive beyond a general diagnosis of septicemia and Actinomyces infection of lung, liver, and spleen. Observations for fecal firmness scores revealed no evidence of diarrhea, and there were no dietary treatment effects on fecal firmness score for any individual week or for mean fecal firmness scores for the overall trial (Table 4; P>0.20).

There were no effects of PAB on growth rate, feed efficiency, or pig BW during the 5-wk trial (Table 4; P>0.25). Trend analysis indicated a quadratic response (P

Implications

Three products were evaluated as potential alternatives to antimicrobial growth promoters in weanling pig diets. Two of these products, a MOS derived from yeast cell wall and a probiotic consisting of dried cultures of Bacillus subtilis and licheniformis, are commercially approved for use in swine diets. The third product, a PAB, has not previously been evaluated in animal diets. Under our experimental conditions, none of these products proved to be effective in improving growth performance or feed efficiency in weanling pigs. Carbadox, an antimicrobial growth promoter that has been approved in the U.S. for use in pig diets since 1975, did improve growth performance in each of the two trials in which it was evaluated. These results suggest that the products assessed in these trials hold limited potential for competitive replacement of traditional antimicrobial growth promoters in pigs.

Acknowledgments

Appreciation is expressed to Alltech Inc. (Nicholasville, KY), Chr. Hansen Biosystems Inc. (Milwaukee, WI), and Donlar Life Sciences (Bedford Park, IL) for financial support of this research. The skillful animal husbandry and technical assistance of Charles Babb, Hannah Cooper, Terry Lee, Phillip Taylor, and Teresa Vaughan is also gratefully acknowledged.

1The research reported herein was conducted as a component of Project VA-135586, Virginia Agricultural Experiment Station and U.S. Department of Agriculture cooperating.

Literature Cited

1. Anonymous. 2001. 2001 Feed Additive Compendium. Miller Publishing Co., Minnetonka, MN.

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

3. Davis, M. E., D. C. Brown, C. V. Maxwell, Z. B. Johnson, and R. A. Dvorak. 2001. Efficacy of mannanoligosaccharide (Bio-Mos) as a complete or partial replacement for zinc oxide in the diets of weanling pigs. J. Anim. Sci. 79(Suppl. 2):78 (Abs.).

4. Davis, M. E., C. V. Maxwell, E. B. Kegley, B Z. de Rodas, K. G. Friesen, D. H. Hellwig, and R. A. Dvorak. 1999. Efficacy of mannanoligosaccharide (Bio-Mos) addition at two levels of supplemental copper on performance and immunocompetence of early weaned pigs. J. Anim. Sci. 77(Suppl. 1):63 (Abs.).

5. Dvorak, R., and A. Jacques. 1998. Mannanoligosaccharide, fructooligosaccharide and carbadox for pigs days 0 - 21 postweaning. J. Anim. Sci. 76(Suppl. 2):64 (Abs.).

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

7. Estienne, M. J., W. A. Douet, J. M. Harter-- Dennis, T. G. Hartsock, M. B. Solomon, and C. R. Barb. 2000. Growth performance and adipose tissue deposition in barrows fed n-- methyl-d,l-aspartate. J. Anim. Sci. 78:2504.

8. Estienne, M. J., J. M. Harter-Dennis, M. Newcombe, C. R. Barb, and J. P. McMurtry. 1994. Effect of n-methyl-D,L-aspartate (NMA) on circulating concentrations of hormones associated with growth in swine and broilers. In Proc. Assoc. 1890 Inst. Res. Directors 10th Biennial Res. Symp., New Orleans, LA. p 44.

9. FASS. 1999. Guide for Care and Use of Agricultural Animals in Agricultural Research and Teaching. (1st Rev. Ed.). Federation Anim. Sci. Soc., Savoy, IL.

10. Harter-Dennis, J. M., M. J. Estienne, and P. McMurtry. 1994. Effect of feeding n-- methyl-D,L-aspartic acid (NMA) on the growth and body composition of broiler chickens. Poultry Sci. 73(Suppl. 1):75 (Abs.).

11. Hill, G. M., D. C. Mahan, S. D. Carter, G. L. Cromwell, R. C. Ewan, R. L. Harrold, A. J. Lewis, P. S. Miller, G. C. Shurson, and T. L. Veum. 2001. Effect of pharmacological concentrations of zinc oxide with or without the inclusion of an antibacterial agent on nursery pig performance. J. Anim. Sci. 79:934.

12. Kinnersley, A. M., L. P. Koskan, D. J. Strom, and A. R. Y. Meah. 1994. Composition and method for enhanced fertilizer uptake by plants. U.S. Patent no. 5,350,735. U.S. Patent and Trademark Office, Washington, D.C.

13. Kyriakis, S. C., V. K. Tsiloyiannis, J. Vlemmas, K. Sarris, A. C. Tsinas, C. Alexopoulos, and L. Jansegers. 1999. The effect of probiotic LSP 122 on the control of post weaning diarrhea syndrome of piglets. Res. Vet. Sci. 67:223.

14. NAHMS. 2002. National Animal Health Monitoring System. Swine 2000 Part II: Reference of Swine Health and Health Management in the United States, 2000. U.S. Dep. Agric. Anim. Health Inspection Serv., Fort Collins, CO.

15. NRC. 1998. Nutrient Requirements of Swine. (1011, Rev. Ed.). Natl. Acad. Press, Wahington, D.C.

16. Pettigrew, J. E. 2000. Bio-Mos effects on pig performance: A review. In Biotechnology in the Feed Industry, Proc. 16th Annu. Symp. T. P. Lyons and K. A. Jaqcues (Eds.). p 31. Nottingham University Press, Nottingham, U.K.

17. Roof, M. D., and D. C. Mahan, 1982. Effect of carbadox and various dietary copper levels for weanling swine. J. Anim. Sci. 55:1109.

18. Rozeboom, D. W., D. T. Shaw, J. E. Pettigrew, and A. Connolly. 2001. Comparative effects of mannanoligosaccharide and an antibiotic in nursery diets on performance of pigs reared on three different farms. J. Anim. Sci. 79(Suppl. 2):79 (Abs.).

19. SAS. 1995. Statistical Analysis System Guide. (Version 6; 3rd Ed.). SAS Institute, Inc., Cary, NC.

20. Smith, R. 1999. Antibiotic bans, regulations may stop development of drugs. Feedstuffs 71(13):l.

21. 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, U.K.

22. Thrasher, G. W., J. E. Shively, C. E. Askelson, W. E. Babcock, and R. R. Chalquest. 1969. Effects of feeding carbadox upon the growth and performance of young pigs. J. Anim. Sci. 28:208.

23. Turner, J. L., S. S. Dritz, and J. E. Minton. 2001. Review: Alternatives to conventional antimicrobials in swine diets. Prof. Anim. Sci. 17:217.

24. Yen, J. T., A H. Jensen, N. H. Bajjalieh, and V. D. Ladwig. 1976. Effects of Methyl-3-- (2-quinoxalinylmethylene) carbazate-N^sub 1^,N^sub 4^-- dioxide on nitrogen and energy digestibility in and performance of young pigs. J. Anim. Sci. 42:375.

25. Yen, J. T., J. A. Nienaber, and W. G. Pond. 1987. Effect of neomycin, carbadox, and length of adaptation to calorimeter on performance, fasting metabolism and gastrointestinal tract of young pigs. J. Anim. Sci. 65:1243.

26. Yen, J. T., and W. G. Pond. 1990. Effect of carbadox on net absorption of ammonia and glucose into hepatic portal vein of growing pigs. J. Anim. Sci. 68:423.

A. F. HARPER2, PAS, and M. J. ESTIENNE

Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University,

Blacksburg, VA 24061

2To whom correspondence should be addressed: alharper@vt.edu

Copyright American Registry of Professional Animal Scientists Dec 2002
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