The new precision stewards? A research agenda for ethical, legal and social aspects of antimicrobial resistance

Karen M. Meagher, PhD

7/19/2022

If only traditional susceptibility testing took less time. If only there was a way to get the most personalized microbial profile into the hands of treating clinicians faster. Then the devastating conflict between missing sepsis or generating a new superbug ― between saving this patient or sparing future generations ― would dissolve. Narrow-spectrum, tailored treatment would become standard of care.

This is the promise of precision stewardship: the right drug, at the right dose, at the right time, for every patient. And the molecular tools that can make it possible are rapidly advancing: next-generation sequencing to optimize de-escalation phylogenetics to anticipate the next variant and maybe even mRNA vaccines to break open the decades-long discovery void.

Current U.S. patient burdens would be reduced: 35 million or more lives per years saved, hospital stays shortened and an estimated $35 billion in annual economic losses recouped. (1-3) Perhaps even there will be hope for mitigating global health inequities, to ease at least one of the heavy burdens that migrant and refugee communities disproportionately shoulder. (4)

If this sounds too promising, that is probably because those in infectious diseases and public health know that expectations for technological solutions can be exaggerated. (5) Antimicrobial resistance is a tangled puzzle of a problem. Like many infectious diseases, the etiology of pathogenesis is varied, and development of resistance does not fit a simple pattern. Furthermore, an aspect of inevitability marks the characterization of antimicrobial resistance. Wherever there are infections, we will use antimicrobial treatments; wherever there is exposure, we generate selective pressures for the development of resistance. We cannot avoid antimicrobial resistance entirely ― but we can slow it down.

Potential health gains and social and ethical challenges

The precision health era will undoubtedly include public and population health gains. (6) Already rapid diagnostic testing has shown the potential to perform on key stewardship goals, including time to de-escalation and reduced hospital stay. (7) Meanwhile, molecular epidemiology can also improve hospital outbreak response, including by pinpointing a source of exposure. (8)

And yet, already, precision methods have also raised social and ethical challenges ― as technological advances often do. Phylogenetic analysis in HIV surveillance has raised questions about how to balance concerns about unintended disclosure of personal information and privacy with public health benefit. (9) Dropping newer, more accurate, technologies into health organizations marked by fears of liability and retaliation for reporting hospital-acquired infections is a recipe for exacerbating, not dissolving, clinicians’ moral worries. (10)

Precision stewardship will come with some improvements in care and benefit for future generations. However, antimicrobial prescribing is a hallmark example of the implementation challenges changing medical practice. Adding new technologies ― and new forms of expertise such as genomics and computational biology ― into the mix will not make matters simpler.

AMR requires solutions that acknowledge both the perils and promise of new molecular technologies. Moreover, we should be cognizant of how the context in which pathogen genomic technologies will be introduced differs from the development of human genetics. What if, in contrast to human genetics, such technological promise is stymied, due to similar market failures that have characterized antimicrobial drug development? Luckily, we do not have to wonder what a wide-ranging multidisciplinary, and innovative research portfolio might look like.

A multidisciplinary call to action

Calls for social science and AMR collaborations are already on the rise. The stage is already set to continue establishing and addressing the critical knowledge and collaborative gaps needed to move stewardship forward. Like other public health challenges, the social determinants of resistance are complex, intertwined and require coordination that confounds the capacity of many policy levers.

Recognition of this problem is leading to articles that focus on the disperse and underfunded social science research on AMR. (11,12) The social turn of stewardship also involves a normative shift, reframing AMR as an ethical challenge. (13,14) As a result, those who care about AMR are left with a complex multidisciplinary call to action ― to address empirical, policy, and ethical gaps in how we understand and address the rise of AMR and its mitigation.

What can ethics, specifically, offer those most engaged in the work of stewardship? First, ethics offers language to name our troubles. Problems are always more disturbing ― and isolating ― when we cannot name them. Embracing an ethos of stewardship acknowledges the need to develop a moral vocabulary that does not downplay or deny the subjectivity of judgement or the reality of tradeoffs. Second, applied ethics employs multidisciplinary problem-solving not only by recognizing the multifaceted causes of social problems, but because disciplinary training enculturates us into a mindset for framing problems and solutions. Multidisciplinarity checks these biases and leverages the strengths of multiple lenses.

The legacy of human genetics research

The U.S. Human Genome Project has a companion investment in research on the ethical, legal and social implications (ELSI) of genetics, spanning decades. Out of the challenges of old problems such as eugenics — and new problems such as genetic literacy — the field of ELSI scholarship was born. More recently, a variety of efforts to organize something akin to an ELSI agenda for AMR have been organized.

For example, the International Network for AMR Social Science (INAMRSS) coordinates academic centers advancing inquiry on these topics. At a global level, the World Health Organization, the World Organization for Animal Health, the Food and Agriculture Organization of the United Nations, and the United Nations Environment Program have created the Quadripartite, a cross-sectoral and global effort to coordinate a One Health approach to AMR mitigation.

In turn, groups like INAMRSS and the Quadripartite will challenge ELSI scholars to grow beyond a narrower focus on advances in human genetics. The need to engage with the global health aspects of AMR will also accompany a need to confront the ongoing reluctance of related fields, like bioethics, to center their agendas around problems of patient need, systemic forms of injustice, and to embrace global governance and human rights frameworks that help translate social analyses into policy solutions. This mutual capacity for expanding our evidence base and critically examining public health and ethical imperatives suggests an exciting future for the ELSI of AMR collaboration.

Disclaimer: This work was made possible by the Center for Individualized Medicine at Mayo Clinic. The views here are those of the author and do not reflect the positions of Mayo Clinic.

References

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