Antibiotic resistance (ABR) poses an urgent public health risk. High rates of ABR have been noted in all regions of the globe by the World Health Organization. ABR develops when bacteria are exposed to antibiotics either during treatments in humans or animals or through environmental sources contaminated with antibiotic residues (Figure, Panel A). Spread beyond those administered antibiotics occurs through direct contact with the infected or colonized person or animal, through contact or ingestion of retail meat or agricultural products contaminated with ABR organisms, or through the environment. ABR bacteria spread from individuals to populations and across countries (Figure, Panel B).

The right to health is enshrined in the constitution of the World Health Organization and numerous other international agreements. Yet today, an estimated 5.7 million people die each year (Table 1) from treatable infectious diseases, most of which are susceptible to existing antimicrobials if they were accessible. These deaths occur predominantly among populations living in poverty in low- and middle-income countries, and they greatly exceed the estimated 700,000 annual deaths worldwide currently attributed to antimicrobial resistance (AMR). Ensuring universal appropriate access to antimicrobials is not only a critical part of realizing the right to health, it is necessary for mobilizing effective collective action against the development and spread of AMR.

The dangers presented by antibiotic resistance (ABR) have now established themselves as a global health security issue. From an international policy perspective, three key pillars have been established: responsible access, conservation, and innovation. These pillars are intrinsically linked, meaning that any attempt to address one must take into account the implications for the other two.

An urgent need exists to address the innovation failure in ABR. In the field of anti-bacterials, the pipeline remains anemic in terms of therapeutics with novel mechanisms of action, new drug classes and strategies involving radically different, innovative approaches. The key reasons for this failure have already been well established. The slow development of new antibiotics is the result of a poor and uncertain commercial market and scientific challenges in research and development (R&D).

Antibiotic development and usage, and antibiotic resistance in particular, are today considered global concerns, simultaneously mandating local and global perspectives and actions. Yet such global considerations have not always been part of antibiotic policy formation, and those who attempt to formulate a globally coordinated response to antibiotic resistance will need to confront a history of heterogeneous, often uncoordinated, and at times conflicting reform efforts, whose legacies remain apparent today. Historical analysis permits us to highlight such entrenched trends and processes, helping to frame contemporary efforts to improve access, conservation and innovation.

Antibiotic resistance presents a classic example of the “tragedy of the commons.” In this eponymous tragedy, the commons — shared, public access lands — are overgrazed because farmers can send their livestock onto the land at a zero price. The “tragedy” occurs because overgrazing destroys the land and reduces its ability to provide fodder. The application to antibiotics is obvious: the use of antibiotics creates selection pressure leading to increased proportions of resistant bacteria in the patient and the environment. The increase in frequency of resistant organisms diminishes the effectiveness of antibiotics in treating future infections; thus, the long-term value of the antimicrobial resource is reduced.

Antimicrobial resistance is a critical public health challenge, and the contribution of the widespread use of antimicrobials in food animals to bacterial drug resistance and human infection demands greater policymaker attention. Global consumption of antimicrobials in food animal production by 2030 is projected to rise by two-thirds due to increases in both food animal production and demand for animal products. In the United States (U.S.), the volume of antibiotics sold for use in food-producing animals is at least three times greater than that sold for human use. A One Health approach that emphasizes the connections among the health of humans, animals, and the environment is needed to address antibiotic resistance in an integrated manner. This approach holds the promise of collaboration across multiple disciplines, including doctors, veterinarians, food safety professionals, and environmental health experts.

Antibiotic resistance (ABR) is a common-pool resource challenge like those that global environmental scholars have been addressing for decades. Just like clean air, fish stocks, and oceans, antibiotic effectiveness shares the two defining qualities of a common good: it is rivalrous in that it is limited or subtractable upon use, and it is non-excludable in that it is very difficult to stop people from abusing them inappropriately. This is because each use of antibiotics increases the likelihood that affected bacteria will adapt and evolve in ways that makes them less susceptible to these bacteria- harming antibiotics. The natural development of resistance is what separates antibiotics from most other medicines — the use of which do not affect the effectiveness of these medicines for others.

Most proposals for new international agreements aim to address important global challenges. If the goal is to solve problems, then the value of these agreements depends on their ability to influence the world — to shape norms, constrain behavior, facilitate cooperation, and mobilize action. A recent review of empirical studies has suggested that many international agreements fail to achieve their aspirations. The review indicates that the form in which states make commitments to each other — through an international legal agreement or through other means — may not be as important as commonly thought. It is the content of the commitments and how these are supported by mechanisms to encourage implementation that matter the most. When developing proposals for new international agreements, like the one that has recently been proposed to address antibiotic resistance (ABR), attention to implementation mechanisms should therefore be equal to if not greater than the attention paid to its form.

Adopting international legal agreements for every global health challenge is not a good idea. Such an enterprise would require unprecedented political mobilization and resources that are impossible to sustain, and it would lead to further fragmentation in global health governance. International legalization also has its costs and trade-offs, including potentially devastating dark sides that we have tallied elsewhere.

Yet we believe that calls for an international legal agreement on antibiotic resistance (ABR) are important and that such an agreement is in fact much needed for the future of global health. We came to this conclusion based on a reasoned assessment of the facts before us — the potential benefits, costs, and trade-offs of an ABR legal agreement — and consideration of four criteria we previously proposed for prospectively evaluating proposals for new global health treaties.3 We came to this conclusion despite previously expressing concerns about adopting new international legal agreements on global health issues.

This article assesses which policies for addressing antibiotic resistance (ABR) as part of a multi-pronged approach would benefit from legalization through an international legal agreement. Ten candidate policies were identified based on a review of existing literature, especially The Lancet Series on Antimicrobial Resistance (AMR), The Lancet Infectious Diseases Commission on AMR, and the World Health Organization (WHO) Global Action Plan for AMR. These policies were then grouped under the headings of access, conservation, and innovation.

Each of the ten policies were assessed using four criteria developed by Hoffman, Røttingen, and Frenk to help consider why their legalization may be helpful, necessary and/or justified. These criteria are: (1) the problem has a significant transnational dimension; (2) the goal justifies the coercive nature of law; (3) the outcome is likely to be beneficial; and (4) legalization represents the best commitment mechanism among competing alternatives.

The nature and effectiveness of any international legal agreement is heavily shaped by the forum in which it is negotiated and implemented. This includes both the substantive content that global policymakers agree upon and the subsequent state compliance with those provisions. Forums differ in their institutional characteristics, thereby providing unique opportunities and costs for participating actors. Forums may have different mandates, capacities, cultures, members, and legal processes — all of which ultimately affect distributions of power and influence. These differences then shape how issues are framed, the content of agreements as they are negotiated, and the incentives states have to comply with any obligations.