Towards an international treaty on antimicrobial resistance.

• Author: Hoffman, Steven J.
• Position: 7th National Health Law Conference

ANTIMICROBIAL RESISTANCE (AMR) is a transnational and multi-sectoral issue that requires global collective action, since individual states cannot fully address the threat that migrating "superbugs" pose to their citizens. Understanding the underlying global market and governance failures that prevent collective action makes it clear that an international legal response is needed to tackle this challenge. An international AMR treaty could promote access, conservation, and innovation for antimicrobials by designating universally appropriate use standards, mobilizing financial resources, coordinating national responses, and setting surveillance expectations. This article expands upon previous proposals for development of an AMR treaty as a mechanism for coordinating states to safeguard sustainable access to effective antimicrobials. Specifically, this article identifies the functions needed to address AMR globally which individual countries cannot achieve on their own; the policies that would most benefit from international legalization as opposed to other approaches; as well as a roadmap to transform these functions and their implementation mechanisms into components of a treaty. We argue that an international treaty is the most suitable platform for achieving global collective action on AMR, with standards for responsible use and surveillance requiring enforced legalization (core policies); funding for access, infrastructure, and infection control measures benefitting from legalization (supportive policies); incentives for innovation being included to contribute to a grand bargain (incentivizing policies); and implementation mechanisms to ensure the treaty's text has real-world effects.

LA RESISTANCE ANTIMICROBIENNE EST un probleme transnational et multisectoriel qui exige une action collective mondiale etant donne que les Etats ne peuvent combatire a titre individuel la menace que represente la propagation des > pour leurs citoyens. Une fois qu'on a circonscrit les failles sous-jacentes au marche et a la gouvernance mondiales qui freinent cet engagement collectif, on constate le caractere imperatif de relever ce defi au moyen d'une reponse juridique d'envergure internationale. Dans cette optique, un traite international en matiere de resistance antimicrobienne pourrait promouvoir l'acces, la conservation et l'innovation relativement aux antimicrobiens, en definissant des normes d'utilisation appropriee universelles en mobilisant des ressources financieres a cette fin, en coordonnant des reponses nationales et en fixant des attentes pour la surveillance. Cet article extrapole a partir des propositions precedentes en vue d'elaborer un traite en matiere de resistance antimicrobienne, qui assurerait la coordination entre Etats afin de preserver un acces durable aux medicaments antimicrobiens efficaces. Cet article identifie en particulier les fonctions necessaires pour contrer la resistance antimicrobienne a l'echelle mondiale, ce que les pays ne peuvent realiser, a titre individuel; les politiques qui beneficieraient le plus de la legalisation internationale par rapport a d'autres approches; de meme qu'une feuille de route permettant de transformer ces fonctions et leurs mecanismes de mise en oeuvre en composantes propres a un traite. Nous soutenons qu'un traite international est la plate-forme la plus susceptible de favoriser l'emergence d'une action collective mondiale en matiere de resistance antimicrobienne, comprenant des normes regissant une utilisation responsable et une surveillance exigeant une legalisation appliquee (politiques essentielles); le financement de l'acces, l'infrastructure, et les mesures de controle des infections beneficiant de la legalisation (politiques de soutien); les incitatifs a l'innovation afin de favoriser une veritable entente (politiques d'incitation); et les mecanismes de mise en oeuvre afin de veiller a ce que le texte du traite entrame des consequences concretes.

1. Introduction II. Part I: Global Interventions Needed to Respond to AMR that Countries Cannot Implement Individually A. Leadership and Stewardship: Strategic Planning of the Global Health System B. Ensuring Provision of Global Public Goods: Discovery, Development, and Delivery of New Health Tools C. Management of Externalities: Reduction of Negative Health Effects that Transcend State Borders D. Direct Country Assistance: Improving the Unequal Distribution of Health Problems and Resources III. Part II: Which Interventions Would Benefit From Legalization and Which Would Not? A. Conservation Policies 1. Prohibiting the Use of Antimicrobials for Growth Promotion or Routine Preventive Measures in Animals 2. Regulating Antimicrobial Prescription and Availability for Humans 3. Designating Human-only Classes of Antimicrobials 4. Strengthening and Coordination of Surveillance Systems and Laboratory Capacity 5. Strengthening of Infection Prevention Practices 6. Providing Education on Effective Antimicrobial Use to Health Professionals and Patients 7. Prohibiting the Marketing and Promotion of Antimicrobials B. Access Policies 1. Mobilizing Financial Resources for Infrastructure in Resource-poor Regions 2. Funding for Access to Appropriate Antimicrobials in Resource-poor Regions C. Innovation Policies 1. Funding and Incentives for Innovation for Medical Technologies Combatting AMR D. Core, Supportive, and Incentivizing Policies IV. Part III: How Can We Turn These Interventions Into Components of a Treaty? A. Key Principles B. Substantive Content C. Implementation Mechanisms D. Which Mechanisms Are the Most Helpful? 1. Global Institution 2. Pooled Funding Mechanism 3. Special Rapporteur 4. Penalties V. Conclusion I. INTRODUCTION

   Antimicrobial resistance (AMR) is an evolutionary mechanism by which bacteria, viruses, parasites, and fungi evolve to no longer be susceptible to antimicrobial medicines, thereby rendering these treatments ineffective. (1) This natural adaptation is artificially accelerated by the inappropriate overuse, misuse, and abuse of antimicrobials in humans and animals. Accelerating AMR has many consequences, such as prolonged infection periods, increased mortality, greater spread of infection, and higher healthcare costs. (2) For instance, in 2014, resistant infections were responsible for 50,000 deaths worldwide, and the rates of resistance continue to increase. It is projected that by 2050, the costs associated with AMR could cumulatively reach $100 trillion USD if no action is taken. (3) This issue is compounded by limited innovation in the field, which has caused the rate of novel treatment development to slow.

   One high-profile example is the evolution of methicillin-resistant Staphylococcus aureus (MRSA). In 2005, MRSA was responsible for 94,000 hospital-acquired infections, which led to 19,000 deaths in the United States. (4) The spread of resistant strains is increasingly prominent in low and middle-income countries (LMICs), as a lack of access to antimicrobial treatments and varying levels of hospital infection prevention and control measures contribute to the proliferation of MRSA and other resistant infections. Recently, it has been discovered that the prevalence of MRSA in hospitals in Asian countries is on average 674%. (5)

   The World Health Organization (WHO) has recognized AMR as a global threat since the 1950s and has advocated for the implementation of numerous recommendations and action plans by its member states. (6) However, there has been little progress in sustaining antimicrobial effectiveness and improving access to antimicrobials worldwide. Today, AMR is still recognized as one of the most pressing global health threats and it is widely accepted that global collective action is required to address key elements of the issue. (7) Yet global efforts to conserve the effectiveness of existing antimicrobials and to invent new ones remain inadequate and fragmented.

   To many people this is shocking. But from a political economy perspective, this insufficient response is entirely rational and predictable. It stems from several game-theoretic problems and global governance and market failures in how antimicrobials are developed and made available worldwide. (8)

   To simplify, the problem essentially boils down to a tragedy of the commons, whereby all countries would benefit over the long term from effective limits on antimicrobial use, but individual countries are incentivized to not impose costly limits over the short term. (9) Such problems are often seen in the environmental sector, where we see the world struggle to manage common-pool resources such as limited carbon emissions in the atmosphere and clean oceans. The key is that every country is incentivized to maximize their short-term interests, which leads to free-riding by countries on every other country's efforts. Individual countries that do choose to implement effective resource stewardship, end up incurring costs without the guarantee that long-term benefits will be obtained due to the free-rider problem and the potential spread of resistant-microbes from other countries. In this case, AMR is further exacerbated by global market failures, whereby there is a misalignment of public and private interests. As a result, antimicrobials are a scarce resource in LMICs where they are unaffordable, and oversupplied in wealthier contexts where they are not used appropriately. The vast social cost of drug misuse is unfortunately too often eclipsed in the minds of patients and their clinicians by their potential benefits--no matter how unlikely those benefits may be, such as the widespread use of bacteria-fighting antibiotics to address viral infections. (10) Although there is strong evidence that certain national policies can limit AMR, the growth of international travel and trade impedes their effectiveness in any single country. (11) Globalization has led to more cases of resistant-microbes spreading seamlessly across national...