Antimicrobial Use in Livestock and the Problem of Bacterial Resistance in Humans

Certain antimicrobials used for treatment or growth promotion in agriculture are also used for disease control in humans. Others select for cross-resistance in bacteria to antimicrobials used in human medicine. Microbiological and clinical evidence is mounting that resistant bacteria or resistance determinants might be passed from animals to humans, resulting in infections that are more difficult to treat.

There is enough evidence to cause concern. It is unrefuted that the use of antimicrobials leads to the selection of resistant bacteria and that the scope of the emerging problem depends, among other things, on duration of exposure to and concentration of the antimicrobial.

Some countries report that more than 50 percent of their total output of antimicrobial compounds is used in agriculture. Most are applied to food animals in subtherapeutic doses as growth promoters, which boost the utilization of the genetic potential for growth of pigs and poultry, improve feed conversion, and reduce waste product output from intensive livestock production.

Medical Impact of the Use of Antimicrobials in Livestock Production

Antimicrobials are used in animals as growth promoters (in subtherapeutic doses), prophylactically for disease prevention (for example, after commingling of animals from different farms), or therapeutically for treatment of infections. Adverse consequences of selecting resistant bacteria in animals include: an increase in the prevalence of resistant bacteria in animals; the transfer of resistant pathogens to humans via direct contact with animals or through the consumption of contaminated food or water; the transfer of resistance genes to human bacteria; an increase in the incidence of human infections caused by resistant pathogens; and potential therapeutic failures in animals and humans.

Salmonella

There is direct evidence that antimicrobial use in animals selects for antimicrobial-resistant nontyphoid Salmonella serotypes. These bacteria have been transmitted to humans in food or through direct contact with animals. Antimicrobial resistance limits the therapeutic options available to veterinarians and physicians for the subset of clinical cases of nontyphoid Salmonella that require treatment. A recent example is a clone of S. typhimurium DT104, resistant to ampicillin, tetracycline, streptomycin, chloramphenicol, and sulphonamides, which has become prevalent in many countries including the United Kingdom, Germany, and the United States.

Following the introduction of fluoroquinolones for use in food-producing animals, the emergence of Salmonella serotypes with reduced susceptibility to fluoroquinolones in humans has become a cause for particular concern.

Campylobacter

Following the introduction of fluoroquinolones for use in poultry, there has been a dramatic rise in the prevalence of fluoroquinolone-resistant Campylobacter jejuni isolated in live poultry, poultry meat, and from infected humans. Moreover, prior to any use in poultry, no resistant strains were reported in individuals with no previous exposure to quinolones. Fluoroquinolone-resistant C. jejuni has been associated with therapeutic failures in humans.

Enterococci

The use of avoparcin as a growth-promoting feed additive in animal husbandry has contributed to the reservoir of transferable resistance genes to glycopeptides, including vancomycin, in the commensal enterococci of animals.

Glycopeptide-resistant enterococci from animals can reach humans via the food chain. Although glycopeptide resistance genes have been shown to be widely disseminated, the extent to which the gene pool in animals contributes to the prevalence of glycopeptide-resistant commensal enterococci in humans has not been quantified.

Glycopeptide-resistant enterococci cause serious infections in hospitalized immune-impaired patients. In this setting, they contribute to increased morbidity and mortality, in part because of limited therapeutic options. This medical impact would be greatest in countries where vancomycin is used intensively.

There is concern that there will be increased dissemination of glycopeptide resistance genes to Enterococcus faecalis and their spread to other gram-positive organisms, particularly to multiresistant Staphylococcus aureus for which vancomycin is the drug of last resort. Due to the limited number of agents available for the treatment of glycopeptide-resistant enterococci, antimicrobial agents not previously used in humans are being sought, including drugs from classes currently used as growth promoters in animals. Therefore, the selection of further resistance in enterococci is undesirable, e.g., streptogramin resistance due to use of virginiamycin as a feed additive in animals.

Escherichia coli

Multiresistant Escherichia coli have been selected by the use of broad-spectrum antimicrobials in both livestock and humans. The development of antimicrobial resistance in E. coli creates problems due to their high propensity to disseminate antimicrobial resistance genes. Resistance genes have been traced from E. coli in animals to E. coli in humans. Certain E. coli are foodborne pathogens, and most of these strains are currently susceptible to antimicrobials. Should therapy be required, it could be compromised by the development of resistance in these strains.

World Health Organization
1997
Report of a WHO Meeting, Berlin, Germany