Antimicrobial use and resistance in animals and human beings

The study in The Lancet Planetary Health by Tang and colleagues1Tang KL Caffrey NP Nóbrega DB et al.Restriction in the use of antibiotics in food-producing animals and its associations with antibiotic resistance in food-producing animals and human beings: a systematic review and meta-analysis.Lancet Plan Health. 2017; 1: e316-e327Summary Full Text Full Text PDF PubMed Scopus (393) Google Scholar is an impressively comprehensive work on one of the most pressing health issues currently acknowledged worldwide: the fight against antimicrobial resistance (AMR). In this complex, multifactorial problem, the Article specifically focusses on the role of antimicrobial use on AMR in food-producing animals and human beings, which has become the subject of increased attention over the past decade.2European Centre for Disease Prevention and ControlEuropean Food Safety AuthorityEuropean Medicines AgencyECDC/EFSA/EMA first joint report on the integrated analysis of the consumption of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from humans and food-producing animals.EFSA J. 2015; 13: 4006Crossref Scopus (161) Google Scholar, 3European Centre for Disease Prevention and ControlEuropean Food Safety AuthorityEuropean Medicines AgencyECDC/EFSA/EMA second joint report on the integrated analysis of the consumption of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from humans and food-producing animals—Joint Interagency Antimicrobial Consumption and Resistance Analysis (JIACRA) Report.EFSA J. 2017; 15: 4872Crossref Scopus (240) Google Scholar Though from an insider's point of view it might hardly seem surprising, this meta-analysis now unequivocally shows that reducing veterinary antimicrobial use leads to a decrease in AMR in animals; and also that veterinary antimicrobial use is not operating in an isolated animal setting but also affects the occurrence of AMR in human beings. Although the varying quality of the studies assessed in this analysis might justly be argued to weaken conclusions on an individual study level, the authors are right to highlight the consistency of their findings overall; hence, convincingly showing that any doubting or second guessing of these major conclusions is no longer defendable. Care should be taken to interpret the reported overall percentage decrease within the context of this study, From a scientific point of view, this study should be viewed as an extra stimulus to drive further research—to unravel the many aspects that have emerged in recent years showing how complex the associations and roles of different reservoirs (eg, animals, in-contact humans, non-contact humans, and the environment) and different processes (eg, use of antimicrobials, development of resistance, spread of resistance, and transmission of resistance) are in reality.4Madec J-Y Haenni M Nordmann P Poirel L Extended-spectrum b-lactamase/AmpC- and carbapenemase-producing Enterobacteriaceae in animals: a threat for humans?.Clin Microbiol Infect. 2017; (published online Jan 29.)DOI: 10.1016/j.cmi.2017.01.013Summary Full Text Full Text PDF PubMed Scopus (141) Google Scholar Although this study shows that a reduction in the use of antimicrobials in animals leads to a reduction of AMR in human beings, the question of exactly what is changing remains. An altered risk of transmission of AMR strains or determinants from animals to human beings seems the better explanation of the observations made, rather than a direct effect of development and spread of AMR in human beings.4Madec J-Y Haenni M Nordmann P Poirel L Extended-spectrum b-lactamase/AmpC- and carbapenemase-producing Enterobacteriaceae in animals: a threat for humans?.Clin Microbiol Infect. 2017; (published online Jan 29.)DOI: 10.1016/j.cmi.2017.01.013Summary Full Text Full Text PDF PubMed Scopus (141) Google Scholar Molecular epidemiological studies should provide the necessary answers, and the effect of any such transmissions on the human resistome on the short and long term needs to be clarified. This discussion imposes an important warning: caution should be taken not to overly shift the focus of the problem of AMR in human beings on the use of antimicrobials in animals. It is important to call veterinary medicine to account for its role in the prevalence of human AMR, yet the exact role that the use of antimicrobials in animals has on human antimicrobial resitance is still insufficiently understood and should not be used to divert attention from the responsibilities in human medicine in relation to cautious antimicrobial use in humans. Another open question the authors identify is the benefit that can be expected from different interventions. In our opinion, the study somewhat under-exposes the very large policy differences existing in different regions of the world, and it might be interpreted as suggesting that banning use of antimicrobials, rather than reducing their use, might be the best answer. However, with such large policy differences, the results from the study by Tang and colleagues might be very differently interpreted in different regions. It seems only reasonable to advocate the prohibition of antimicrobial use in feed for growth promotion worldwide, as has been implemented in Europe for over a decade. At the same time, several countries, European as well as non-European, have shown that antimicrobial stewardship, on the basis of detailed information on antimicrobial use, AMR, or both, rather than strict inhibition, might lead to desired reductions).5European Medicines AgencyEuropean Surveillance of Veterinary Antimicrobial ConsumptionSales of veterinary antimicrobial agents in 30 European countries in 2015.http://www.ema.europa.eu/docs/en_GB/document_library/Report/2017/10/WC500236750.pdfDate: 2007Google Scholar, 6Dorado-García A Mevius DJ Jacobs JJ et al.Quantitative assessment of antimicrobial resistance in livestock during the course of a nationwide antimicrobial use reduction in the Netherlands.J Antimicrob Chemother. 2016; 71: 3607-3619Crossref PubMed Scopus (70) Google Scholar, 7The Netherlands Veterinary Medicines InstituteUsage of antibiotics in agricultural livestock in the Netherlands in 2016. Trends and benchmarking of livestock farms and veterinarians.http://www.autoriteitdiergeneesmiddelen.nl/en/publicationsGoogle Scholar The veterinary sector should be given a chance to at least try to reduce the use of antimicrobials in animals rather than be imposed to do so.8Daeseleire E De Graef E Rasschaert G et al.Antibiotic use and resistance in animals: Belgian initiatives.Drug Test Anal. 2016; 8: 549-555Crossref PubMed Scopus (15) Google Scholar WV reports that the Data Analysis Unit of AMCRA receives funding from a private source (Belpork vzw) as well as from the Belgian Federal Agency for Medicines and Health Products, with respect to the tasks that are done on their account, being quantification (AB Register) and reporting (Sanitel-Med) of farm-level antimicrobial usage data collected by the monitoring systems. However, inside and outside this function the Data Analysis Unit works autonomously without any interference on the views expressed and the positions taken. Furthermore, the Data Analysis Unit works autonomously from the Board of Directors and the Steering Committee from AMCRA. JD reports no competing interests. Restricting the use of antibiotics in food-producing animals and its associations with antibiotic resistance in food-producing animals and human beings: a systematic review and meta-analysisInterventions that restrict antibiotic use in food-producing animals are associated with a reduction in the presence of antibiotic-resistant bacteria in these animals. A smaller body of evidence suggests a similar association in the studied human populations, particularly those with direct exposure to food-producing animals. The implications for the general human population are less clear, given the low number of studies. The overall findings have directly informed the development of WHO guidelines on the use of antibiotics in food-producing animals.