1. Effect of antimicrobials in food- producing animals on pathogen load Systematic review of published literature Michael Goodman MD, MPH Exponent®, Alexandria, VA January 23, 2002 Michael Goodman MD, MPH Exponent®, Alexandria, VA January 23, 2002

2. Issue Antibiotics in food-producing animals could decrease microbial shedding. (NRC 1999) However, Most antibiotics only effective against certain bacteria (e.g., gram–positive cocci). Therefore, Antibiotics may disturb normal microbial ecosystem resulting in an increase in certain bacteria (e.g., Salmonella). (CVM 1999) Antibiotics in food-producing animals could decrease microbial shedding. (NRC 1999) However, Most antibiotics only effective against certain bacteria (e.g., gram–positive cocci). Therefore, Antibiotics may disturb normal microbial ecosystem resulting in an increase in certain bacteria (e.g., Salmonella). (CVM 1999)

3. Concern Animals carrying increased amounts of pathogens (pathogen load) at the time of slaughter may present an increased risk for contamination of food and resulting human illness (CVM 1999).

4. Objective To review and analyze published literature evaluating the effect of antimicrobials in food-producing animals on pathogen load.

5. Methods: Literature search 33 literature databases searched –Medical (e.g., Medline, Toxline) –Agricultural (Agricola, Agris, etc.), –Food literature (Foodline, Food Adlibra), –Veterinarian and zoological (e.g., Zoological Record Online®) –General scientific Search terms –antibiotics AND pathogen AND food –animals AND food AND pathogen load –food-producing animals AND antibiotics –other combinations 33 literature databases searched –Medical (e.g., Medline, Toxline) –Agricultural (Agricola, Agris, etc.), –Food literature (Foodline, Food Adlibra), –Veterinarian and zoological (e.g., Zoological Record Online®) –General scientific Search terms –antibiotics AND pathogen AND food –animals AND food AND pathogen load –food-producing animals AND antibiotics –other combinations

6. Methods: Data extraction Animal species under study Antibiotic in question Dose of antibiotic Study design Bacterial species evaluated Results Animal species under study Antibiotic in question Dose of antibiotic Study design Bacterial species evaluated Results

7. Classification of studies * Two studies conducted separate experiments on three species: chickens, swine and calves.

8. Challenge studies: swine & calves Antibiotics included: –chlor- and oxytetracyclin –Apramycin –Neomycin –Penicillin –Ceftiofur –Carbadox. All studies used S. typhimurium as inoculum. No evidence of antibiotics increasing Salmonella shedding. (Table 1, handout) Antibiotics included: –chlor- and oxytetracyclin –Apramycin –Neomycin –Penicillin –Ceftiofur –Carbadox. All studies used S. typhimurium as inoculum. No evidence of antibiotics increasing Salmonella shedding. (Table 1, handout)

9. Challenge studies: poultry All 6 studies from the Houghton Laboratory, UK showed significant increase in Salmonella shedding in chickens that received antibiotics. Shedding in these birds was also longer than in controls. Results were particularly strong for avoparcin. (Table 2, handout) These results were not replicated by others. All 6 studies from the Houghton Laboratory, UK showed significant increase in Salmonella shedding in chickens that received antibiotics. Shedding in these birds was also longer than in controls. Results were particularly strong for avoparcin. (Table 2, handout) These results were not replicated by others.

10. Challenge studies: poultry (continued) Gustafson (1981) –Avoparcin increased Salmonella shedding only after single inoculation early in life. –Serial inoculations and inoculations later in life showed no impact of avoparcin. Holmberg et al. (1984) –No increase in Salmonella shedding after avoparcin alone. –Combined use of avoparcin and coccidiostat monensin caused increased Salmonella shedding. (Table 2) Gustafson (1981) –Avoparcin increased Salmonella shedding only after single inoculation early in life. –Serial inoculations and inoculations later in life showed no impact of avoparcin. Holmberg et al. (1984) –No increase in Salmonella shedding after avoparcin alone. –Combined use of avoparcin and coccidiostat monensin caused increased Salmonella shedding. (Table 2)

11. Challenge studies: poultry (continued) Other studies examined effect of: –virginiamycin (Abou Youssef et al. 1983) on Salmonella –nosiheptide (Benazet et al. 1980) on Salmonella and E. coli –flavophospholipol and salinomycin (Bolder, 1999) on Salmonella, Campylobacter and Clostridium No increase in pathogen load found. (Table 2) Other studies examined effect of: –virginiamycin (Abou Youssef et al. 1983) on Salmonella –nosiheptide (Benazet et al. 1980) on Salmonella and E. coli –flavophospholipol and salinomycin (Bolder, 1999) on Salmonella, Campylobacter and Clostridium No increase in pathogen load found. (Table 2)

12. Observational studies Little evidence that antibiotics added to animal feed substantially affect bacterial shedding. Only exceptions are studies that used penicillin. (Table 3) Little evidence that antibiotics added to animal feed substantially affect bacterial shedding. Only exceptions are studies that used penicillin. (Table 3)

13. Limitations of studies 1.Only Salmonella studied extensively. 2.Challenge studies may not represent real life conditions. 3.Only swine and chickens underwent sufficient study. 4.The diet or genetic line of animals that may affect the pathogen load and may explain data variability are not considered. 1.Only Salmonella studied extensively. 2.Challenge studies may not represent real life conditions. 3.Only swine and chickens underwent sufficient study. 4.The diet or genetic line of animals that may affect the pathogen load and may explain data variability are not considered.

14. Conclusions Most data indicate that the use of antibiotics in food-processing animals is generally not associated with increased pathogen load. Studies of Salmonella inoculation in chickens show disagreement. Overall the data have to be considered too limited to draw firm conclusions. Most data indicate that the use of antibiotics in food-processing animals is generally not associated with increased pathogen load. Studies of Salmonella inoculation in chickens show disagreement. Overall the data have to be considered too limited to draw firm conclusions.