"Growth Promotant" Antibiotics

Antibiotic use in pork production facilities comes in many forms and has been very controversial for a couple of decades due to consumer fear that it may be contributing to an increased occurrence of antibiotic resistant bacteria. Strains of antibiotic resistant bacteria could potentially infect humans and be virtually untreatable with typical medications available today. This fear led to the ban on the inclusion of sub-therapeutic antibiotics in livestock feed in Denmark and some consumers have called for similar legislative action in the United States (Casewell et al, 2003). One of the primary reasons for using antibiotics is to improve growth performance in finisher pigs so understanding how antibiotics impact the microflora within the gut of pigs is important so we can better understand the consequences of a ban on antibiotic use in the future. There was a spike in antibiotic resistance observed in Denmark following the antibiotic ban which leads to the question of whether or not this was the correct decision in the long run.

There are four main categories of antibiotic use in swine production today: therapy, metaphylaxis, prophylaxis, and growth promotion (Schwarz et al, 2001). These are all forms of usage involving the killing of living microorganisms, usually bacteria, by attacking a specific functional part of the cell structure (Carlson and Fangman, 2000).

The usage of antibiotics for therapeutic treatment generally refers to the treatment of specific animals for ailments or diseases based on observed symptoms. In swine production, however, pigs are frequently treated without showing overt symptoms because of the potential for rapid transmission of infectious diseases and the impracticality of only treating individuals within grouped pens of pigs. (Schwarz et al, 2001). Instead, rooms of a barn or more typically the whole barn will often be treated if a certain number of animals exhibit symptoms, thus taking a proactive treatment approach to prevent potentially more animals from becoming sick. The key point here is that all the animals are being administered antibiotics at a therapeutic dose level (McEwen and Fedorka-Cray, 2002). This method of treatment is called metaphylaxis and would involve the addition of medication to feed or water when the condition has been diagnosed among pigs in a barn (Schwarz et al, 2001).

Similar to metaphylaxis, prophylaxis is the preventative administration of antibiotics in feed or water, especially for use post-surgery or during high-risk periods during the growing period (Schwarz et al, 2001). In pork production, this would be important when individuals are making the transition to new groups or during a change in the environment or nutrient supply, such as at weaning. This practice and the use of antibiotics as growth promotants are the current two primary uses for antibiotics in swine production (McEwan and Fedorka-Cray, 2002).

The final category of antibiotic use in livestock production is as a growth promotant. They are fed at subtherapeutic levels to reduce specific populations of bacteria within the intestine during the life of the pig, resulting in improved performance largely through improved feed utilization(Carlson and Fangman, 2000). As mentioned previously, it is thought that subtherapeutic antibiotics may also have a prophylactic function in preventing pathogen spread and helping to maintain a healthy gut by supporting specific beneficial bacterial populations (McEwan and Fedorka-Cray, 2002).

Based on the diverse roles that antibiotics play in swine production, it is readily apparent that choosing the correct antibiotic is critical within a production system. There are many different types of bacteria, and antibiotics have been divided into multiple categories which help in the selection of the correct antibiotic.

The efficacy of an antibiotic on various pathogens and bacteria is tested in the lab on plates. A variety of mediums are available, each with small limitations, but they used to support the bacterial population in question in a standard laboratory setting before the bacteria are treated with different antibiotics. From this, antibiotics are classified by which bacteria they can effectively kill (Ericsson and Sherris, 1971).

First, there are both narrow spectrum and broad spectrum antibiotics. Narrow spectrum antibiotics target specific bacteria whereas broad spectrum antibiotics target a wider range of bacteria (Merck Veterinary Manual, 2008). The assumed benefit to targeting specific bacterial populations would be the effective elimination of these bacteria with minimal impact on other populations. The use of broad spectrum antibiotics has the potential of reducing overall medication with a larger range of effectiveness in fewer doses.

Bacteria are also classified as either Gram-positive vs. Gram-negative based on the makeup of their cell walls and their identification with the Gram staining method. These two groups are sufficiently different that antibiotics are often classified as being effective against either Gram-positive or Gram-negative bacteria. Most bacteria which are impacted by antibiotic growth promotants are Gram-positive whereas the bacteria which can develop resistance to human drugs are often Gram-negative (Casewell et al., 2003). Treating a Gram-positive bacteria with a Gram-negative antibiotic will not be effective against Gram-positive bacteria and is a waste of both time and money. The same occurs when Gram-positive antibiotics are used to treat Gram-negative bacteria. This is what has been observed in Denmark following the ban on antibiotics and why it is important to identify the goal of administering antibiotics prior to choosing the specific drug.

Subtherapeutic antibiotics in feed influence a number of factors which ultimately contributes to improved growth and nutrient utilization in the pig. The interaction between antibiotics and microflora primarily occurs in the lower portion of the small intestine where the pH is more favorable to the microbial population than near the emptying of the stomach (Hill, 2011). Ideally, organisms that reside in the gut and compete with the pig for nutrients are suppressed by the antibiotics, while those organisms which are beneficial to the pig flourish from lack of competition. This would include the bacteria which can cause an enteric infection. The remaining microflora are beneficial to the pig by enhancing cellulose digestion (which the pig is incapable of itself) or the metabolism/production of other nutrients which might be required by the animal (Carlson and Fangman, 2000). In addition, some intestinal components such as bile salts and amino acids which the gut would naturally recycle are more available because they are not degraded by the suppressed microrganisms. Finally, antibiotics act to reduce the intestinal wall thickness which leads to increased nutrient absorption and greater efficiency of nutrient utilization (Carlson and Fangman, 2000).

Higher efficiency of nutrient digestion and increased nutrient absorption represents a conceptual source of increased growth gain for grower/feeder pigs, but there are even larger gains for nursery/weaning pigs. Although the inclusion of subtherapeutic antibiotics has not been shown to increase or significantly change the specific activity of digestive enzymes in the young (Collington et al, 1990), it has been shown to statistically significantly reduce mortality and prevent diarrheal conditions which are observed in increasing quantities among antibiotic free production in Denmark and Spain (Casewell et al, 2003). This reduction in mortality combined with the increased growth and performance with antibiotic represents potential economic gains for the farmers as well through increased number of pigs weaned or higher weight of pigs weaned.

The three most commonly used antibiotics in feed according to a 2006 USDA National Animal Health Monitoring System survey were chlortetracycline (52.6% of farms), tylosin (44.2% of farms), and bacitracin (29.1% of farms) (USDA-NAHMS, 2007) and each of them serve a different purpose for pigs. Chlortetracylcin is from the family of tetracyclines. It passes through the stomach and is absorbed in the small intestine. Once absorbed, it is distributed to the majority of cells before excretion via the kidneys and some back through the gastrointestinal tract. This is a very broad acting antibiotic and is used for treating a variety of bacterial infections (Merck Veterinary Manual, 2008). Tylosin is from the family of macrolides which specifically targets Gram-positive bacteria by preventing protein production through reversible binding on a ribosomal subunit, blocking the production of the proteins required by the bacteria to grow and reproduce (Merck Veterinary Manual, 2008). Additionally, tylosin targets mucolytic bacteria which contribute to mucosal barrier damage and destruction of the intestinal wall (Collier et al, 2003). Similarly to tylosin, bacitracin is involved in suppressing cell wall synthesis by bacteria, thus acting as a bacteriocide. It primarily impacts Gram-positive bacteria and is not absorbed by the intestine (Merck Veterinary Manual, 2008).

Despite the push for a reduction in antibiotic use, the data from Denmark suggests that a better appreciation for how antibiotics function may lead to more intelligent and judicious usage of antibiotics. However, a full ban of antibiotics does not appear to be a viable solution based on the sharp increase in antibiotic resistance in Denmark after the banning of some antibiotics currently in use in other countries. Antibiotics have been shown to effectively reducing disease and control the negative impact from certain bacterial populations on animal health and we need to be able to keep using them to some extent.

1. Casewell, M., C. Friis, E. Marco, P. McMullin, I. Phillips. The European ban on growth-promoting antibiotics and emerging consequences for human and animal health. 2003. Journal of Antimicrobial Chemotherapy. Volume 52:159-161.
2. Schwarz, S., C. K. Ehrenberg, T.R. Walsh. Use of antimicrobial agents in veterinary medicine and food animal production. 2001. International Journal of Antimicrobial Agents. Volume 17:431-437.
3. McEwen, S. A., P. J. Fedorka-Cray. Antimicrobial Use and Resistance in Animals. 2002. Journal of Clinical Infectious Diseases. Volume 34 (Suppl. 3):S93-106.
4. Carlson, M. S., T. J. Fangman. Swine Antibiotics and Feed Additives: Food Safety Considerations. Revised January 2000. Missouri University Extension Publication, Swine Feeding. Accessed online 14 January 2011.
5. Ericsson, H. M., J. C. Sherris. Antibiotic Sensitivity Testing: Report of an International Collaborative Study. 1971. Acta Path Microbiol Scand 1971;217(Suppl)1–90
6. Merck Veterinary Manual. 9th Edition. 2008. Merck, Inc. Accessed online 17 January 2011.
7. Hill, A. Journey into the Small Intestine. 2011. Lecture in AS 630.02 at The Ohio State University. 12 January 2011.
8. Collington, G.K., D.S. Parker, D.G. Armstrong. The influence of inclusion of either an antibiotic or a probiotic in the diet on the development of digestive enzyme activity in the pig. 1990. British Journal of Nutrition. Volume 64:59-70.
9. Zimmerman, D.R. Role of Subtherapeutic Levels of Antimicrobials in Pig Production. 1986. Journal of Animal Science. Volume 62(Suppl. 3):6-17
10. USDA NAHMS. Part II: Reference of Swine Health and Health Management Practices in the United States, 2006. 2007. USDA-APHIS. Accessed online 17 January 2011.
11. Collier, C.T., J.D. van der Klis, B. Deplancke, D. B. Anderson, H. R. Gaskins. Effects of Tylosin on Bacterial Mucolysis, Clostridium perfringens Colonization, and Intestinal Barrier Function in a Chick Model of Necrotic Enteritis. 2003. Antibimicrobial Agents and Chemotherapy, Vol. 47, No. 10, pg. 3311-3317.