Maximizing Voluntary Compliance in Antimicrobial Stewardship Programs: A Critical Factor for Effective Intervention

Antimicrobial drug resistance (AMR) has reached a critical level of importance; if unchecked, it will reverse decades of advances in human and animal health. The Centers for Disease Control and Prevention (CDC) estimates that AMR bacteria kill approximately 23,000 people in the U.S. each year and 2 million are clinically infected. As a result, AMR costs the U.S. economy approximately $70 billion annually. In addition to clear threats to public health, AMR poses immediate challenges to the security of our agricultural economy because AMR can also decrease the effectiveness and diminish the availability of antimicrobials useful against bacteria that cause significant food-animal disease. Vibrant and effective public and animal-health systems depend on approaches to prevent and cure infectious diseases. Solutions to AMR are of paramount importance to the U.S. Worldwide, many have called for a wholesale reduction in the use of antimicrobials, citing evidence that there is either overuse or misuse of these products. In multiple jurisdictions, regulatory approaches to reduce 'overuse' or 'misuse' proceed either on the basis of defining what is not considered judicious use, point to scientific data supporting a prohibition order for a specified product (sometimes, a change in new drug approval processes, or else invoke the use of the precautionary principle to protect the efficacy of a product in the absence of firm scientific evidence. In the United States, several recent Food and Drug Administration (FDA) documents of note, whose major purpose is to ensure the prudent approval and use of antimicrobials in veterinary medicine and animal agriculture, have been published (e.g., Guidance for Industry (GFI) #152, #159, #209, and #213; to a major extent, these consist of non-binding recommendations). In 2003, GFI #152 established the risk assessment framework under which new animal drug approvals would proceed. This process included guidance to drug sponsors that qualitatively categorized antimicrobials as to criticality, but also established aspects of hazard, release, exposure, and consequence assessment that were previously less well defined for microbial hazards. A simplified framework for examining the risk of release of resistant bacteria and their determinants from agricultural facilities as part of a broader quantitative risk assessment framework presents a compelling opportunity to aim to achieve 'zero' release of resistant bacteria (or determinants) above baseline or background risk levels. Since animal production can only take ownership of what is under its control this seems the logical place to start a discussion of what constitutes antimicrobial stewardship, and how this can be promoted into the future. Our overall long term goal is to identify, evaluate, and implement practical, effective and widely adoptable interventions for managing antimicrobial resistance (AMR) among enteric bacteria; in this project, our focus is on developing - through a systems-based stakeholder-centered process - science-based voluntary stewardship programs suited to animal production. In pursuit of this overall goal we focus our efforts - herein on beef and dairy cattle production systems - and directly address the following supporting objectives in this proposal: 1) recruit key stakeholders to qualitatively explore the essential components and systems framework to maximize voluntary compliance with highly effective antimicrobial stewardship programs, 2) conduct empirical field studies to provide key microbiological, production, economic, and social science decision support data, 3) perform qualitative and quantitative modeling needed to design, test, and improve essential decision support tools, and 4) engage key stakeholders to further develop, refine and communicate highly effective decision support tools to enhance their voluntary adoption and diffusion and to maximize antimicrobial stewardship. Both AMR and the likelihood of unintended consequences of uninformed, broad-sweeping attempts to control it pose a direct threat to the sustainability of U.S. agriculture. In our integrated standard grant project, we will design, evaluate and deliver efficacious and implementable interventions to mitigate AMR, based on voluntary stewardship principles and guidelines, facilitated by science-based decision tools and multiple and broad stakeholder input and support.