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A Review - The Use of Antibiotics in Food Production Animals: Does This Cause Problems in Human Health? By Peter Collignon, Infectious Diseases Physician and Microbiologist, Director Infectious Diseases Unit and Microbiology Department, The Canberra Hospital. Professor, Canberra Clinical School. Australian National University and the University of Sydney.

Significant Science on Antibiotic Resistance: An Annotated Bibliography
Overwhelming scientific evidence now indicates that bacteria are developing antibiotic resistance as a result of antibiotic use in animal agriculture. Evidence has accumulated despite the inadequate public health monitoring and surveillance programs in the United States. There is every reason to believe that as further studies are done, and as monitoring improves, the link between antibiotic use in agriculture and the emergence of difficult-to-treat disease will only become more evident. Since antibiotic resistance is worsening in the interim, many public health organizations and experts are calling for action now to limit antibiotic overuse in agriculture to protect public health.

Some of the key scientific evidence is contained in the following publications.

Antibiotic Resistance Generally

  1. Barker Keith F. Antibiotic resistance: a current perspective. J. Clin. Pharmacol. 1999; 48: 109-124. Reviews various mechanisms of antibiotic resistance, and identifies current clinical problems along with possible solutions and future developments. Includes good tables of antibiotics used in the United Kingdom, examples of bacterial strains with inherent resistance, and combinations of bacteria and antibiotics in the presence of which mutational resistance is likely to develop.
  2. Levy Stuart B. The Challenge of Antibiotic Resistance. Scientific American. March, 1998. General discussion of antibiotic resistance, how bacteria become resistant, how antibiotic exposure promotes resistance, and how resistance might be reversed. Explores excessive use of antibiotics and considers the environmental impact of that overuse.

Agricultural Use of Antibiotics and Antibiotic Resistance

  1. National Academy of Sciences/Institute of Medicine Global Board on Health, Microbial Threats to Health: Emergence, Detection, and Response. National Academies Press. 2003. The report succinctly summarizes data on agricultural use of antibiotics, concluding that “Clearly, a decrease in antimicrobial use in human medicine alone will have little effect on the current situation. Substantial efforts must be made to decrease inappropriate overuse in animals and agriculture as well” (p. 207).
  2. Alliance for the Prudent Use of Antibiotics, The Need to Improve Antimicrobial Use in Agriculture: Ecological and Human Health Consequences. Clinical Infectious Diseases 2002; 34: S71-144. Over a two-year period, a panel of experts in human and veterinary medicine, public health, microbiology, and other disciplines reviewed more more than 500 studies relating to agricultural uses of antibiotics. The panel concluded that “elimination of nontherapeutic use of antimicrobials in food animals and agriculture will lower the burden of antimicrobial resistance”.
  3. Goforth Robyn L., Carol R. Goforth. Appropriate Regulation of Antibiotics in Livestock Feed. Boston College Environmental Affairs Law Review. 2000. 28(1). Very good review of non-therapeutic uses of antimicrobials in food animals and the impact on human health. Discusses the regulatory process for approving new drugs for use in animal agriculture, and suggestions for how to curb the spread of antibiotic resistance.
  4. Khachatourians George G. Agricultural use of antibiotics and the evolution and transfer of antibiotic-resistant bacteria. Canadian Medical Association Journal. Nov. 3, 1998; 159: 1129-36. Excellent scientific review of trends in antibiotic use in animal husbandry and agriculture in general. The development of resistance is described as well as the mechanisms utilized.
  5. Levy Stuart B. Antibiotic Use for Growth Promotion in Animals: Ecologic and Public Health Consequences. J. Food Protection. July 1987. 50(7): 616-620. General discussion of sub-therapeutic use of antibiotics in animals, the cases of the spread of resistance from animals to man, reservoirs of resistance genes, multiple resistances and alternative measures.
  6. Salyers A. How are human and animal ecosystems interconnected? Ontario Ministry of Agriculture, Food and Rural Affairs. Discusses the debate over agricultural use of antibiotics as growth promoters, whether antibiotic use in agriculture selects for resistant bacteria, the potential impact on farmers and their animals, antibiotic-resistant bacteria in the food supply, and the transfer of resistance genes in the human colon.

Evidence for Resistant Bacteria Transferred from Animal Agriculture to Humans

  1. Dunne E.F., P.D. Fey, P. Kludz, R. Reporter, F. Mostashari, P. Shillam, J. Wicklund, C. Miller, B. Holland, K. Stamey, T.J. Barrett, J.K. Rasheed, F.C. Tenover, E.M. Ribot, F.J. Angulo. Emergence of Domestically Acquired Ceftriaxone-Resistant Salmonella Infections Associated with AmpC B-Lactamase. J. Americal Medical Association. Dec. 27, 2000. 284(24): 3151-3154. Summarizes national surveillance data for Salmonella infections in the U.S. resistant to the antibiotic, ceftriaxone, and describes the mechanisms of resistance. Ceftriaxone is an important treatment for severe Salmonella infections, especially in children.
  2. Endtz HP, GJ Ruijs, B van Klingeren, WH jansen, T van der Reyden, RP Mouton. Quinolone resistance in Campylobacter isolated from man and poultry following the introduction of fluoroquinolones in veterinary medicine. J. Antimicrob. Chemother. 1991; 27(2): 199-208. Tested 883 strains of Campylobacter bacteria isolated between 1982 and 1989 from human stool and poultry products for quinolone resistance. Campylobacter isolated from poultry increased in resistance from zero to 14 percent in that time, while resistance in human isolates rose from zero to 11 percent. Results suggest that the increase is mainly due to use of the fluoroquinolone, enrofloxacin, in poultry.
  3. Fey Paul, Thomas J. Safranek, Mark E. Rupp, Eileen F. Dunne, Efrain Ribot, Peter C. Iwen, Patricia A. Bradford, Frederick J. Angulo, and Steven H. Hinrichs. Ceftriaxone-resistant Salmonella infection acquired by a child from cattle. New Engl. J. Medicine. April 27, 2000. Analysis of Salmonella enterica serotype typhimurium isolated from a 12-year old boy with fever, abdominal pain and diarrhea. Results indicated that the ceftriaxone-resistant bacteria isolated from the child was indistinguishable from a Salmonella isolate taken from cattle on his father’s farm.
  4. Levy Stuart B, George B FitzGerald, and Ann B Macone. Changes in intestinal flora of farm personnel after introduction of a tetracycline-supplemented feed on a farm. New Engl. J Medicine. Sept. 9, 1976. 295(11): 583-588. In this controlled study, chickens were fed tetracycline-supplemented feed (tet-feed). Within 1 week the chicken’s intestinal flora included organisms almost entirely resistant to tetracycline. Within 5-6 months 31.3% of farm dwellers had fecal samples with organisms more than 80 percent tetracycline-resistant; increased bacterial resistance to multiple antibiotics was also observed.
  5. Lyons Robert W, Cathryn L Samples, Hema N DeSilva, Kathryn A Ross, Ernest M Julian, Patricia J. Checko. An epidemic of Resistant Salmonella in a Nursery… Animal to human spread. JAMA. Feb. 8, 1980. 243(6). The case of a pregnant woman, infected with Salmonella heidelberg, who worked on a farm until 4 days before delivery. Her baby subsequently developed mild diarrhea, as did 2 others sharing the hospital nursery. Salmonella heidelberg was isolated from each, and in all cases was resistant to chloramphenicol, sulfamethoxazole, and tetracycline. The strain originated from a herd of infected farm animals.
  6. Molbak Kare, Dorte Lau Baggesen, Frank Moller Aarestrup, Jens Munk Ebbesen, Jorgen Engverg, Kai Frydendahl, Peter Gerner-Smidt, Andreas Munk Petersen and Henrik C. Wegener. An outbreak of Multidrug-resistant, Quinolone-resistant Salmonella enterica serotype typhimurium DT104. New Engl J Med. November 4, 1999. Study details an outbreak of multidrug-resistant Salmonella in Denmark where 25 culture-confirmed cases were found; 11 patients were hospitalized and 2 patients died. The primary source of the resistant strain was a Danish swine herd.
  7. Ojenyiyi A.A. Direct transmission of Escherichia coli from poultry to humans. Epidem. Inf. 1989. 103: 513-22. Tested 864 Escherichia coli isolates from workers at a poultry research farm in Denmark and 216 strains from poultry attendants in a commercial poultry farm in the city and poultry isolates were studied. Similar resistance patterns were found in the workers and the birds they worked with.
  8. Smith K.E., J.M. Besser, C.W. Hedberg, F.T. Leano, J.B. Bender, J.H. Wicklund, B.P. Johnson, K.A. Moore, M.T. Osterholm. Quinolone-Resistant Campylobacter jejuni Infections in Minnesota, 1992-1998. New Engl J Med. May 20, 1999. 340(20): 1525-1532. The Minnesota Department of Health tested nearly 5,000 human isolates of Campylobacter for resistance to the quinolone antibiotic, nalidixic acid. Isolates found resistant to nalidixic acid then were tested for resistance to ciprofloxacin. Human isolates of C. jejuni resistant to quinolones rose from 1.3% in 1992 to 10.2% in 1998. Rising prevalence of resistant Campylobacter was temporally associated with the U.S. licensure of sarafloxacin in 1995 and enrofloxacin in 1996 for use in poultry. A portion of the infected had travelled to Mexico which has a high rate of usage of various fluoroquinolones. The study also looked at Campylobacter isolates from retail chickens.
  9. Van der Bogaard Anthony, Ellen E. Stobberingh. Epidemiology of resistance to antibiotics: Links between animals and humans. International J. Antimicrobial Agents. 2000. 14:327-335. Discusses avoparcin (an antibiotic similar to human vancomycin) use in animals in certain countries, and the discovery of enterococcal bacteria resistant to vancomycin not only in the exposed animals, but in the surrounding human population outside of the hospital. Also discusses use of nourseothricin and apramycin, resistance to which was identified not only in animal bacteria but also in human commensal bacteria, in zoonotic pathogens like Salmonella and also in strictly human pathogens, like Shigella. Discusses ban on avoparcin in E.U. and significant decreases in vancomycin resistance enterococci in animals and humans. Shows evidence for transfer of resistance genes between bacteria in humans and animals.
  10. Wegener HC, FM Aarestrup, P Gerner-Smidt and F. Bager. Transfer of Antibiotic Resistant Bacteria From Animals to Man. 1999. Acta. Vet. Scand. Suppl. 92: 51-57. Discusses antibiotic resistance in zoonotic bacteria – particularly in Salmonella, Campylobacter, Yersinia and enterohaemorrhagic E. coli (EHEC). Discusses that development of resistant bacteria primarily is driven by the use of antibiotics in animals and to a lesser extent due to use in humans.

Resistant Bacteria & Resistance Genes in Food, Water, Air

  1. Chee-Sanford J.C., R.I. Aminov, I.J. Krapac, N. Garrigues-Jeanjean, and R.I. Mackie. Occurrence and Diversity of Tetracycline Resistance Genes in Lagoons and Groundwater Underlying Two Swine Production Facilities. Applied and Env. Microbiology. April 2001. 67(4): 1494-1502. This study looked at evidence for tetracycline resistant bacteria in lagoons underlying hog farms using tetracycline antibiotics in feed, as well as in the groundwater beneath these lagoons. Determinants of tetracycline resistance were found in the lagoon, in the groundwater up to 250 meters downstream from the lagoons, and in the soil microbiota.

Transfer of Resistance Genes Between Bacteria

  1. Shoemaker N.B., H. Vlamakis, K. Hayes, and A.A. Salyers. Evidence for Extensive Resistance Gene Transfer among Bacteroides spp. and among Bacteroides and Other Genera in the Human Colon, Applied And Environmental Microbiology, 2001, 67: 561–568. Provides evidence that bacteria transfer resistance genes extensively in the human colon. The gram negative bacteria, Bacteroides, accounts for around 25% of bacteris isolated from the colon. Over three decades, the prevalence of Bacteroides strains carrying a certain gene resistant to tetracycline went from 30% to 80%. Evidence also was found that resistant genes are transferred between Bacteroides and gram positive bacteria.

Reversal of Antibiotic Resistance

  1. Aarestrup Frank Moller, and Anne Mette Seyfarth. Effect of intervention on the occurrence of antimicrobial resistance. Acta. Vet scand. 2000; Suppl. 93: 99-103. Discusses reversals of antibiotic resistance following decreased antibiotic use observed in the Netherlands (tetracycline), Germany (VRE reduction), Denmark (avoparcin ban and VRE reduction). Authors note that to date there have not been major negative consequences of removing growth promoter antibiotics from use.

Alternatives/Complements to Agricultural Use of Antibiotics

  1. World Health Organization. Impacts of antimicrobial growth promoter termination in Denmark. 2003: Report number WHO/CDS/CPE/ZFK/2003.1. WHO convened an international panel of experts to conduct an in-depth review of the experience of Denmark – the world’s largest pork exporter – which has pioneered reductions in agricultural use of antibiotics and has developed the world’s most comprehensive data on antibiotic use and antibiotic-resistant bacteria. The panel, which included US experts on agriculture and public health, concluded that Denmark’s phase-out of antibiotic feed additives led to an overall drop in the use of antibiotics in food animals by 54%, and “dramatically reduced” levels of resistant bacteria in animals. The panel also concluded that the phase-out did not adversely affect food safety, environmental quality, or consumer food prices.
  2. Dritz, Tokach, Goodband, and Nelssen. Effects of administration of antimicrobials in feed on growth rate and feed efficiencyof pigs in multisite production systems. J. American Veterinary Medical Association, 2002, 220: 1690-1695. The authors of the study, which was conducted at Kansas State University, found that adding antimicrobials to feed resulted in only a 5% improvement in growth rate among nursery pigs (typically the first 6 to 8 weeks after weaning), and no improvement in growth rate among finishing pigs (the remaining 14 to 18 weeks of production). Adding antimicrobials to feed did not improve feed efficiency (the amount of food needed to result in weight gain) in either nursery or finishing pigs.
  3. Wierup Martin. The control of microbial diseases in animals: alternatives to the use of antibiotics. International Journal of Antimicrobial Agents. 2000. 14: 315-319. Discusses various means to control bacterial infections in farm animals by other means than antibiotic use, including improved hygiene, isolation of sick animals, replacing live breeding animals by semen and embryos, etc.

Other countries

  1. Bager Flemming. DANMAP reports from Denmark (DANMAP 2002, DANMAP 2001, DANMAP 2000, DANMAP 1999): The Danish Integrated Antimicrobial Resistance Monitoring and Research Programme presents the results of resistance monitoring in food animals, foods and humans.
  2. Bager Flemming. DANMAP: monitoring antimicrobial resistance in Denmark. International Journal of Antimicrobial Agents. 2000. 14: 271-274. Describes the Danish system for monitoring antibiotic-resistant bacteria in humans, in animals, the link between the two, and the amount of antibiotics used.
  3. Engberg Jorgen, Frank M. Aarestrup, Diane E. Taylor, Peter Gerner-Smidt, and Irving Nachamkin. Quinolone and Macrolide Resistance in Campylobacter jejuni and C. coli: Resistance Mechanisms and Trends in Human isolates. Emerging Infectious Diseases. Jan-Feb. 2001; 7(1). Review of macrolide and quinolone resistance in Campylobacter strains and tracking of the resistance trends in human clinical isolates in relation to use of these agents in food animals. Good synopsis of when antibiotics were licensed in many countries (for food animals) and good bar graph depicting resistances in many countries.
  4. Martel Jean-Louis, Florence Tardy, Anne Brisabois, Renaud Lailler, Michel Coudert, Elisabeth Chaslus-Dancla. The French antibiotic resistance monitoring programs. International Journal of Antimicrobial Agents. 2000. 14: 275-283. Description of the French antibiotic resistance monitoring program involving testing non-human zoonotic Salmonella for antimicrobial susceptibilities, as well as testing of other bacteria strains pathogenic to beef cattle.
  5. Moreno Miguel A., Lucas Dominguez, Tirushet Teshager, Inmaculada A. Herrero, M. Concepcion Porrero, The VAV Network. Antibiotic resistance monitoring: the Spanish programme. International Journal of Antimicrobial Agents. 2000. 14: 285-290. Description of the Spanish program to monitor antibiotic resistance, including isolates of bacteria from sick animals, as well as from healthy food animals.
  6. Smith Kirk E., Jeffrey B. Bender and Michael T. Osterholm. Antimicrobial Resistance in animals and relevance to human infections. In Campylobacter, 2nd edition; 2000; Chapter 25. Edited by Martin Blaser and Irving Nachamkin. American Society for Microbiology, Washington, D.C. Study focuses on combinations of bacteria resistant to particular antimicrobials looking especially at fluoroquinolone-resistant Campylobacter, and relates the latter to approval in many countries of the fluoroquinolones, sarafloxacin and enrofloxacin, for use in food animals.
  7. Wierup Martin. Preventive methods replaced antibiotic growth promoters: ten years experience from Sweden. Alliance for the Prudent Use of Antibiotics Newsletter 1998; 16(2): 1-2,4. Discusses some of the changes made in Swedish methods for raising farm animals after a ban on the use of antibiotics as growth promoters; the study also reviews some of the difficulties encountered, and the accomplishments.
  8. Wray Clifford, Jean-Claude Gnanou. Antibiotic resistance monitoring in bacteria of animal origin: analysis of national monitoring programmes. International Journal of Antimicrobial Agents. 2000. 14: 291-294. Briefly discusses and gives tables of countries in the European Union and their monitoring systems for antibiotic resistance, including the bacteria which are tested, and the methods used.

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Last updated: 5/10/04