Animal production and antimicrobial resistance in the clinic
Venue: The Lancet

2016 e1 One of the major public health challenges this century is the development of antimicrobial resistance in many important and common pathogens, such as Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus. The Lancet Series on antimicrobials tackles the issue head on by presenting evidence on universal access to antibiotics, sustainability, and eff ectiveness. The Series focuses on the use and misuse of antimicrobials in human medicine but does not ignore other sources of antimicrobial resistance development: waste and contamination from the pharmaceutical industry, animal agriculture, and the natural arms race that has been fought among microbes in the environment since the dawn of evolution. A substantial share of antimicrobial consumption is attributed to animal production. Recent fi ndings conservatively estimate that, from 2010 to 2030, global consumption of antimicrobials in livestock production will increase by two thirds, and that it will double in the rapidly growing economies of Brazil, Russia, India, China, and South Africa. In China, already the largest producer and user of antibiotics in the world, the livestock sector could consume a third of the antibiotics produced worldwide by 2030. Alison Holmes and colleagues suggest that misuse of antimicrobials in animal production is an evident and substantial driver of antimicrobial resistance. Other studies show how the global food trade can obscure the lines that connect antibiotic use in food animal production with antibiotic resistant human infections. The evidence that links antimicrobial use in animal production and the development of antimicrobial resistance in medically important pathogens is growing, thanks largely to advances in genetic analysis which allow the origins of genes conferring such resistance to be traced. Using whole genome sequencing and phylogenetics, an international team of researchers described the evolution of meticillin resistant S aureus (MRSA) in livestock from meticillin susceptible S aureus in humans. This livestockassociated MRSA (clonal complex CC398) now frequently infects people both inside and outside of the livestock industry, and is an unequivocal example of the evolution of a multidrug resistant pathogen that emerged in livestock and was subsequently transmitted to humans. Genetic fi ngerprinting and epidemiological studies have also established links between multidrug resistant urinary tract infections and E coli from poultry. Moreover, a multicountry analysis of the human gut antibiotic resistome showed the abundance of resistant genes to be greatest for those antibiotics also used in animals. Whole genome sequencing of samples along food systems can reveal and begin to quantify the two way traffi c of antimicrobial resistant bacteria between the farm and the clinic, but this will require sampling frames that account for the specifi cities of antimicrobial use, the complexity of environmental transmission pathways, and the vast diversity of animal production systems globally. While molecular epidemiology is bringing new clarity to this issue, some of the strongest evidence that links agricultural antibiotic use to antimicrobial resistance in people comes from simple, natural experiments involving the introduction or withdrawal of antimicrobials from food animals. For instance, the introduction of fl uoroquinolones to broiler chicken production in the USA was associated with a rapid increase in ciprofl oxacin resistant campylobacteriosis in humans. Similarly, the voluntary withdrawal of ceftiofur in ovo injections in broiler chicken production in Canada resulted in a precipitous decrease in human infections caused by third generation cephalosporinresistant Salmonella enterica. Despite these clear examples, there are insuffi cient data to resolve and quantify the total public health burden of antibiotic use in food animal production. Antimicrobials are used for various reasons in animal production, including for growth promotion, disease prevention, and disease treatment. These uses involve diff erent classes of drugs applied at diff erent doses, and their relative importance and methods of implementation vary greatly across animal production systems and in diff erent parts of the world. The subtherapeutic use of antimicrobials to promote growth, in particular, comes under heavy criticism. In 2006, the European Union banned the use of antibiotics for growth promotion in livestock, and indications are, for example in the pork and poultry sectors in Denmark, that the prevalence of antimicrobial resistance among livestock has decreased since then. The use of antimicrobial growth promoters is still hotly debated in the USA, where non binding guidance was issued in 2012 which recommended that livestock producers avoid using antibiotics as growth promoters. Animal production and antimicrobial resistance in the clinic