Session V of the workshop focused on moving from knowledge to action in combating antimicrobial resistance. The session was moderated by James Hughes, professor of medicine and public health at Emory University Rollins School of Public Health. During this session, workshop organizers asked forum members, speakers, and attendees to break into four groups, each focusing on a specific theme: surveillance; stewardship, infection prevention, and behavior modification; basic and applied research and development; and global policy and coordination. Each group was given 1 hour to discuss and explore the top three immediate or short-term actions that could result in the biggest impacts that are feasible and cost-effective against antimicrobial resistance. A member of the Forum on Microbial Threats or speaker of the workshop was assigned to moderate each of the four breakout groups. The moderator for the breakout group on surveillance (Group 1) was Jeffrey Duchin, health officer and chief, Communicable Disease Epidemiology and Immunization Section for Public Health, Seattle and King County, Washington. For the breakout group on stewardship, infection prevention, and behavior modification (Group 2), the moderator was John Rex, chief strategy officer at CARB-X. Emily Erbelding, deputy director of the Division of AIDS at the National Institutes of Health, was the moderator for the breakout group on basic and applied research and development (Group 3). For the breakout group on global policy and coordination (Group 4), the moderator was Suerie Moon, director of research at the Global Health Centre, Graduate Institute of International and Development Studies, Geneva. All speakers and attendees were invited to join the breakout group of their choice. This
chapter summarizes some of the suggested actions that emerged from the breakout groups and reflections on possible next steps by some workshop participants during the final synthesis discussion of the workshop. The ideas that each group came up with should not be construed as collective conclusions or recommendations, and do not necessarily represent the views of all workshop participants, the Forum members, or the National Academies.
Duchin reported for the breakout group on surveillance. The first suggested action, he said, was to optimize data acquisition from existing sources, including
- Antibiotic prescribing patterns,
- Antibiograms from clinical health care facilities and the U.S. Department of Defense,
- Information from clinical laboratories including isolate repositories,
- Information from health care systems on outcomes in patients with antimicrobial drug-resistant infections,
- Information on antimicrobial drug usage both in humans and animals,
- Information from citizen science related to environmental sampling, and
- Data from veterinary diagnostic laboratories (e.g., state diagnostic laboratories for animals, veterinary laboratories, and data from the U.S. Food and Drug Administration).
Duchin suggested that the data acquired could be incorporated into a central data repository in a standardized format for analysis and interpretation, perhaps accompanied by guidelines for interpretation.
According to Duchin, the breakout group’s second suggested action was to improve the standardization of surveillance systems by adopting the recommendations of the World Health Organization (WHO) Advisory Group on Integrated Surveillance for Antimicrobial Resistance. This includes organisms to surveil (and the order of priority), laboratory methods, data quality issues, and methods for sampling and culture. The group’s third suggested action, said Duchin, was to improve and standardize environmental surveillance. This could include locations for obtaining surveillance isolates, surveillance methods, and data collection protocols to accompany guidance. Duchin said that the sampling of farm animals could be more extensive if environmental sampling were a precompetitive process among producers.
Guidance from the Genomic Standards Consortium1 could be included as part of the standardization process around environmental sampling, he said. Finally, Duchin commented on the issue of culture-independent diagnostic testing and molecular methods, emphasizing the need for guidance about how these methods should be used and interpreted, as well as their implications for various aspects of surveillance and response.
Reporting for the breakout group on stewardship, infection prevention, and behavior modification, Rex explained that the discussion was divided into human and veterinary domains. A suggested action applicable to both domains, he said, is the need for more vaccines; this entails everything from funding basic development science to establishing priority vaccine targets. Another suggested action for both domains, Rex said, is building workforce capacity by training health care providers and leadership, as well as establishing standardized curricula that include stewardship and infection prevention.
A suggested action specific to the human domain, said Rex, concerns measuring and reporting data on antimicrobial usage, such as usage by tonnage by a territory and usage by health care providers. Referring to the previous day’s presentation by Jeffrey Linder, Rex noted the simple act of measuring—and telling people you are measuring—coupled with minimal feedback can have an effect on behavior. Rex said that the group highlighted a gap around stewardship and incentive principles for all of the domains of veterinary medicine. Some structure exists for food animals in terms of guidance and incentives, he said, but not for companion animals and aquaculture. He suggested working on how to structure stewardship and incentives for the latter space.
Erbelding reported for the breakout group on basic and applied research and development. The group’s suggested action was to prioritize an ecologic systems biology approach to validate biosignatures, she said. This approach would include measurements from water systems, antibiotic use, and food, among other relevant entities in the ecosystem, and would enable description of the microbiome and of factors that correlate with the resistome, she added. A description of the entire ecosystem would
also enable the identification of the biosignatures of resistance in each compartment, said Erbelding, which could be validated by experimentally perturbing the system in a positive or negative way. Having established this approach and validated the biosignatures, Erbelding said, specific interventions could be tested. For example, it would enable comparisons between various animal food production practices to measure the persistence of effect on the resistome over time. Validated biosignatures could also be used for modeling new approaches in other ecosystems, such as animal management methods, she said.
Reporting for the breakout group on affecting global policy and coordination, Moon explained that the group began by looking at the world of antimicrobial resistance. She described it as “a world of about 10,000 pieces that may or may not fit together into a puzzle.” However, she noted, there may be better ways to frame the issue because of natural overlap of these activities with such things as global health security and universal health coverage. The group discussed the importance of bearing in mind the global political context, Moon said. She predicted that the appetite for big, multilateral solutions may be diminishing, but that we fortunately have a number of broad multilateral plans already in place.
Much of the group’s discussion focused on the activities needed at the transnational level (either at the regional or global levels), but there were no suggestions for further agreements or declarations on this issue, Moon reported. The first suggested activity, Moon said, concerns convening the global community of practice around antimicrobial resistance, with stakeholders from all sectors sharing knowledge and identifying gaps. She said that in particular, it would be very useful to strategically convene smaller groups that could form a transnational network of exchange for sharing and strategizing about concrete, day-to-day practices among private-sector actors, prescribers, stewardship policy makers, and scientific researchers, for example. The second suggested activity is a more concerted coordination of efforts in areas of need, she said. This might include global coordination of economic incentives provided for research and development in health technologies, she continued, as well as the regulatory and policy frameworks within which it occurs. She said that similar global coordination is needed among funders that are building health care capacity at the country level. In terms of the economic actors in agriculture, aquaculture, and other sectors, there is also a need for incentives and frameworks for regulation and policy. She highlighted the importance of “small tweaks or levers of trade policies or trade incentives that can, in fact, change the
behavior of actors without having to resort to necessarily global level plans or strategies.” Finally, the third suggested activity, Moon reported, is the development of monitoring and accountability efforts outside of the existing United Nations (UN) system that may be required to ensure that this global complex system to fight against antimicrobial resistance continues to evolve in a forward direction in line with the global goals, strategies, and action plans that are already in place.
After the moderators reported some suggested actions that emerged from the breakout groups, several workshop participants reflected on potential next steps that could be taken moving forward to counter the threat of antimicrobial resistance. The discussion began with the topic of funding as well as refining and leveraging the message of antimicrobial resistance. David Relman, professor of medicine at Stanford University, noted that the funding system is currently fragmented and not well aligned with the One Health view, and as a result, much of this work suggested by the four breakout groups might be difficult to fund with the existing defined portfolios and disparate priorities of individual institutions. He asked about new types of funding systems or organizational principles that could bring together separate institutions to collaborate on identifying the resources needed to carry out the work proposed. Keiji Fukuda, director and clinical professor at the University of Hong Kong School of Public Health, observed that it is very difficult to create new systems to package together funding and partners at the international level, which may pose a barrier to Relman’s suggestion. Fukuda suggested that there is more potential for success at the country level to leverage antimicrobial resistance as a rallying cry, but the concept of antimicrobial resistance will need to be clarified as a unified concept—with a consistent description—to sustain attention on the issue. He suggested reshaping the concept:
So that we think of antimicrobial drugs in the same way that we think about clean water. . . . We use as much as we need, but we don’t waste it. It’s like food. You eat as much as you need, and you don’t waste it. It’s a concept that people can understand.
Rex suggested that putting antimicrobials in a framework underlined by the notion of security—secure food, secure water, secure antibiotics supply—may help unify the concept.
Jesse Goodman, professor of medicine and infectious diseases at Georgetown University, agreed about the importance of messaging to sustain action against resistance. He noted that ongoing revolutions in science—
from the microbiome to vaccinology to metabolomics—offer new potential to stimulate and sustain interest; similar scientific revolutions have changed the perception of antibiotics in animal agriculture in just a few years, he said. As an attention-getting tactic, Goodman suggested focusing on the threat that untreatable infections pose to basic health system functions that affect everyone in society.
Kumanan Rasanathan, chief of the Implementation Research and Delivery Science Unit at the United Nations Children’s Fund, reflected that strengthening the antimicrobial ecosystem does need that type of unifying banner, but that it needs to be coupled with efforts to penetrate into existing agendas that already have ongoing community action. He used climate change as an example, noting that it has moved forward, not necessarily because people identified with the climate change movement under a unified banner, but because of people acting in their own spheres of interest (e.g., transport planners want to reduce congestion because it is often a key deliverable for them). He suggested inserting surveillance of antibiotic use and outcomes into the huge existing quality improvement agenda to strengthen health systems, particularly in low- and middle-income countries, which already calls for better data systems to improve health systems’ performance. That said, Rasanathan noted, there are specifics that need to remain under the antimicrobial resistance agenda because they cannot be carried out elsewhere.
Sally Davies, chief medical officer for England in the United Kingdom Department of Health, noted that because a report produced by the Interagency Coordination Group on Antimicrobial Resistance is due to the UN Secretary General for the UN General Assembly session in 2018 (see Chapter 2), now is the time to shape the desired changes, targets, structures and so forth for the immediate and longer term. Low-hanging fruit, she suggested, is inserting antimicrobial resistance into all policies (universal health care, tuberculosis, and malaria, for example). Davies expressed concern about a potential schism that could arise if—as some people have suggested—a new UN body or global fund is created for antimicrobial resistance. She noted that this would be a mistake:
We need to see antimicrobial resistance as an underpinning issue that impacts the whole health system and food chain, and we have got to strengthen health systems. But if we are not careful, we will find those who are about the subject starting to have a battle about what the future’s structures are, whether there is enough money—and there isn’t enough money—and where we need a special fund . . . rather than staying together, which we are at the moment, to help people lead better lives and have safer food.
Lonnie King, professor and dean emeritus at The Ohio State University College of Veterinary Medicine, noted a positive shift in the sphere of
antimicrobial resistance toward establishing shared interests. He suggested that despite a common misconception, establishing shared interests does not require compromising if it is mutually agreed that those interests will achieve the best outcome for everyone involved. He said the public represents part of that shared interest, and thus the public should be involved in this effort.
Davies also highlighted the need to engage civil society and create a public face for antimicrobial resistance. Rima Khabbaz, deputy director for infectious diseases at the U.S. Centers for Disease Control and Prevention, similarly suggested promoting its public face:
People have to see antimicrobial resistance as a problem, their problem. . . . The change that we have seen in public safety and what people are saying—[that] it is not acceptable to go to a health care setting to get treated and come up with an adverse event—has changed things. I think with antimicrobial resistance, we need the same—people saying “No, it is not okay; I need the antibiotics protected.”
Goodman agreed that the problem of antimicrobial resistance is so complex and important that both the payoffs and the solutions need to be synergistic across the human, animal, and environment sectors. Similarly, incentivizing product development will require both public–private and government partnerships, he said. To add to the discussion on product development, George Poste, chief scientist of the Complex Adaptive Systems Initiative at Arizona State University-SkySong, commended Rex’s presentation (see Chapter 5) for its pragmatic description of the fragility of the research and development process. He expressed concern that certain predictions—for example, that 10 new antibiotics will be developed by 2020—are not at all feasible. Poste suggested that for the situation to improve, pragmatic policies will need to be developed by drug development experts in direct collaboration with the pharmaceutical industry.
On the topic of data, Peter Daszak, president of EcoHealth Alliance, observed that for gains to be achieved against the problem of resistance, surveillance data will need to be collected in countries other than the United States, where antimicrobials are freely available and unregulated. To better understand the actual level of risk and find solutions, Daszak suggested the pharmaceutical industry should be persuaded to open up their sales and surveillance data. Davies noted that efforts to promote the fight against resistance on the global stage are hampered by the lack of a WHO International Classification of Diseases code for people who have severe morbidity or mortality from antimicrobial resistance, which is a requisite step for standardizing data. Finally, Rasanathan added that while data to inform hard science on usage and behavior are needed, so are data on
policy implications, economic markets impact, and relative impact modeling around different regulatory choices.
King concluded the workshop by reiterating the importance of shaping the concept of antimicrobial resistance, both for unifying efforts and for inflecting the progress that has already been made to galvanize momentum toward future actions that are measurable and impactful. He hoped that the workshop would help stimulate even more action moving forward and achieve big wins in the immediate term.