Submitted to: Foodborne Pathogens and Disease
Publication Type: Peer reviewed journal
Publication Acceptance Date: 9/11/2005
Publication Date: 12/1/2005
Citation: Kim, L.M., Gray, J.T., Harmon, B.G., Jones, R.D., Cray, P.J. 2005. Susceptibility of Escherichia coli from growing piglets receiving antimicrobial feed additives. Foodborne Pathogens and Disease. 2:(4):304-316. Interpretive Summary: Misuse of antimicrobials in both humans and animals can lead to the development of resistant bacteria including those that cause food borne illness. While, illness caused by food borne bacteria typically resolves without complications, if treatment with antimicrobials is necessary, they may not be effective if the bacteria are already resistant to them. Of particular concern is the use of low doses of antimicrobials in standard diets fed to meat producing animals such as pigs, cattle and poultry to promote growth and maintain animal health. We studied the effect of three feed-based antimicrobials (apramycin, carbadox, and tetracycline) on both the development of antimicrobial resistance in normal gut bacteria (Escherichia coli) in growing piglets and piglet growth. Results were compared to control animals fed standard diets without antimicrobials. Fecal samples were cultured for Escherichia coli at regular intervals from all piglets from birth to market weight. Antimicrobial susceptibility profiles of fecal Escherichia coli populations were determined using standard testing methods. Piglets were also weighed when fecal samples were collected. Resistance to tetracycline in Escherichia coli varied widely by sample, group, and trial. However, a significant increase in the percentage of resistant isolates was observed in piglets fed antimicrobials when compared to controls. Resistance to apramycin also increased in piglets when compared to controls. However, upon removal of apramycin, resistance in Escherichia coli declined. Resistance to carbadox remained unchanged after feeding carbadox when compared to controls. Piglets fed low doses of antimicrobials demonstrated improved growth when compared to controls. These data are useful for veterinarians, pharmaceutical manufacturers, and scientists as they devise ways to limit the development of resistance to antimicrobials while maintaining animal health.
Technical Abstract: Objectives: To determine the effect of three feed-based subtherapeutic antimicrobials (FSAs; apramycin, carbadox, and tetracycline) on both the antimicrobial susceptibility of commensal E. coli in growing piglets and animal performance. Materials and Methods: Three replicate trials were conducted using growing piglets fed standard diets with and without subtherapeutic antimicrobials. Fecal samples were cultured for commensal E. coli at regular intervals from all piglets from birth to market. Antimicrobial susceptibility profiles of fecal E. coli populations were determined using a replica-plate method for screening followed by testing with the Sensititre broth microdilution system. Animal performance was also measured. Results: Resistance to tetracycline in E. coli varied widely by sample, group, and trial. However, a significant increase in the percentage of resistant isolates was observed in piglets fed FSAs when compared to controls (P < 0.0001). This increase persisted throughout the growth phases in all trials. In Trials 1 and 3, E. coli resistance to apramycin increased in piglets fed subtherapeutic apramycin when compared to controls, and this difference remained significant over all trials (P < 0.0001). However, upon removal of apramycin, resistance in E. coli declined to baseline levels by Day 75. Resistance to carbadox remained unchanged after feeding carbadox when compared to controls. Piglets fed FSAs demonstrated improved feed efficiency during Phase 4 (P < 0.001), and higher average daily gains in Phases 3 and 4 (P < 0.0001). Discussion: This study highlights the complex network of factors involved in the development of antimicrobial resistance in commensal E. coli. Each of the antimicrobials fed had different effects on the E. coli population of piglets. Tetracycline resistance was highly variable, but selective pressure exerted in animals fed FSAs had a measurable effect on resistant populations, suggesting that tetracycline resistant populations can increase as well as persist. Use of feed-based apramycin resulted in a transient increase in resistance that declined rapidly to baseline levels following its removal. Implications: The development of antimicrobial resistance in zoonotic and commensal bacteria from food animals has resulted in complete cessation of subtherapeutic antimicrobial use in Europe, and proposals in the U.S. to end the use of subtherapeutic antimicrobials in animal feeds. These data suggest that some antimicrobials, such as apramycin, may not lead to the development of persistently resistant populations and may therefore be suitable for continued use. Understanding the effects of different classes of antimicrobials on the antimicrobial resistance of commensal flora will assist in making science-based decisions concerning the future use of feed-based subtherapeutic antimicrobials.