To provide some context for the workshop’s presentations and discussions, Keiji Fukuda, director and clinical professor at the University of Hong Kong School of Public Health, and Sally Davies, chief medical officer for England in the United Kingdom Department of Health, provided their perspectives on harnessing the current global momentum to combat antimicrobial resistance.
During his keynote address, Fukuda reflected on how the issue of antimicrobial resistance has evolved since the 20th century. The discovery of penicillin in 1928 and the introduction of sulfonamides in 1937 ushered in an intense period of scientific discovery related to microbial infections, antimicrobial resistance, and drug development that continues today, said Fukuda. He noted that the 1950s through the 1970s was the “golden period” of antibiotic development, discovery, and production that spawned many of today’s current classes of antibiotics. Since the identification of transferable resistance in the 1950s, he said, an estimated 200,000 articles related to the concept have been published (Davies and Davies, 2010). The same period saw the emergence of national and international efforts to provide scientific guidance and perspectives on resistance, said Fukuda. In 1959, the World Health Organization (WHO) scientific group on antibiotics research first recommended studies on resistance (WHO, 1960), and in 1981, a scientific working group on antimicrobial resistance released a report including guidelines for the appropriate use of antibiotics (WHO,
1981). In 2001, WHO released its Global Strategy for Containment of Antimicrobial Resistance (WHO, 2001). Fukuda added that the Transatlantic Taskforce on Antimicrobial Resistance was formed in 2009, and 2011 saw the release of the European Action Plan,1 the Jaipur Declaration,2 and the World Health Day “Antimicrobial resistance: no action today, no cure tomorrow” policy package.3
The outcome of this scientific work, said Fukuda, has been a plethora of scientific knowledge and guidelines—from WHO, from the World Organisation for Animal Health (OIE), and from the Food and Agriculture Organization of the United Nations (FAO), among others—about preserving the efficacy of antimicrobials. The 1998 World Health Assembly resolution WHA51.17 (Emerging and other communicable diseases: antimicrobial resistance)4 brought to the forefront issues that are only beginning to be grappled with today, he said. Fukuda explained that the resolution formalized concerns about the rapid emergence and spread of human pathogens resistant to available antibiotics, about the increasing inefficacy of available antibiotics and the high cost of the new-generation antimicrobials, and about the potential for extensive use of antibiotics in food production to further accelerate the development of resistance.
There have been major gains in scientific knowledge, concepts, and professional guidance related to antimicrobial resistance, said Fukuda. However, he observed that the issue has been positioned as a complex phenomenon of primarily medical relevance. Although the recent adoption of the One Health approach has broadened its relevance to other fields, he said, the expectation that science will provide an endless supply of new antibiotic drugs remains prevalent. The reality is that the pharmaceutical industry has been losing interest in delivering new medicines because new antibiotic drugs are not financially viable, he cautioned, which is juxtaposed with the continued increase in antimicrobial resistance trends worldwide. The first global survey of antimicrobial resistance that was conducted by WHO in 2014, explained Fukuda, examined a group of hospital and community infections and resistance patterns to study the magnitude of antimicrobial resistance across all WHO regions and countries. The report found high levels of antimicrobial resistance in all regions, he said, as well as significant gaps in surveillance data and underreporting of key concerns
1 The European One Health Action Plan against Antimicrobial Resistance is available at ec.europa.eu/health/amr/sites/amr/files/amr_action_plan_2017_en.pdf (accessed July 31, 2017).
2 The Jaipur Declaration on Antimicrobial Resistance is available at www.searo.who.int/entity/regional_committee/64/rc64_jd.pdf (accessed July 31, 2017).
4 World Health Assembly resolution WHA51.17 is available at archives.who.int/prioritymeds/report/append/microb_wha5117.pdf (accessed July 31, 2017).
such as multidrug-resistant tuberculosis. The report underscored the need for active strategic change and extending engagement beyond the health and science sector, he said, because current approaches are essential but not sufficient.
The One Health approach provides a collaborative concept to broaden engagement beyond the realm of health and science, Fukuda said. FAO, OIE, and WHO are partnering around the One Health concept and actively targeting champions at the highest possible levels in political, economic, security, and business sectors around the world. He reported that these efforts have affected meaningful change by broadening, publicizing, and socializing the discussion about antimicrobial resistance. He pointed to WHO’s global action plan on antimicrobial resistance (WHO, 2015b) as a key development. Although it is essentially a repackaging of principles and guidance that had been created years previously, he said, it represents the outcome of focused diplomatic effort to engage across sectors and with countries at all levels of development. It also laid the foundation for a milestone high-level meeting of the G20 and the United Nations (UN) in 2016, which increased the issue’s legitimacy and formalized countries’ commitment to address antimicrobial resistance. The meeting also mandated an Interagency Coordinating Group on Antimicrobial Resistance (IACG), which is composed of high-level representatives of relevant UN agencies, other international organizations, and individual experts across different sectors, to provide practical guidance for approaches needed to ensure sustained effective global action to address antimicrobial resistance. The gains achieved are political and time limited, Fukuda warned, unless they are built upon through institutional commitment and cooperation across nonhealth public sectors and catalyze further action in the private sector.
Fukuda considered how to capitalize on the momentum of efforts to date and move from knowledge about antimicrobial resistance to the next phase of action. The high-level aims remain unchanged, he said: achieving the lowest possible sustained levels of antimicrobial resistance; developing and producing reliable new technologies, including essential medicines; and providing affordable and equitable access to those technologies. According to Fukuda, there are several foundational elements to emphasize. He noted that antimicrobial resistance needs to become a high-profile social issue—like cancer, tobacco control, or HIV/AIDS—to provide the necessary fuel to drive change. Antimicrobial resistance needs to be familiar and personally relevant to the average person, he added, and not an abstract, far-removed issue that people assume science will remedy. “Socialization” of antimicrobial resistance must be the fundamental driver, Fukuda argued, because popular concern and support will be needed to enable new policies, initiatives, and funding. He reflected, “The concrete challenge is how do you take something that in general is seen as abstract, technical, and distant, almost
like science fiction, and . . . make that personal? How do you humanize it? How do you make it seem like something that has to be dealt with now?” He suggested employing multiple voices, including civil society and media, to recraft the concept as personal, urgent, and potentially reversible with appropriate action.
Fukuda remarked that accelerating the pace of change will require closing certain knowledge gaps. He observed that in public health, evidence sometimes drives action, but insufficient evidence is often cited as justification for slow progress. Critical gaps in information, he said, include the need for a more holistic picture of the epidemiology and the etiology of resistance across the One Health domains, which will allow better allocation of resources and responsibilities. Understanding which interventions are most cost-effective is another gap, he said, as well as strategies for transitioning past the use of antimicrobials for growth promotion in agriculture.
Moving forward, Fukuda urged key groups to be visibly active in their efforts to address antimicrobial resistance. He suggested the following:
- The UN’s IACG should actively engineer cooperation and coordination among sectors.
- FAO, OIE, WHO, and other international organizations should keep the issue of antimicrobial resistance at the forefront, provide strategic advice in addition to technical guidance, and continue to exemplify the One Health approach to partnering.
- Governments should take leadership roles and broaden the involvement of nonhealth agencies, as well as introducing legislation and providing financing. Additionally, the health and agriculture sectors on the national level should work to make knowledge about antimicrobial resistance and best practices normative and to separate profit from the provision of antibiotics.
- Civil society can serve as society’s conscience, scrutinizing and organizing efforts around the inappropriate use of antimicrobials.
- Industry should find ways back into antimicrobial drug production and should internalize access to drugs as an operational concept of production, not a separate issue.
- Funders and academia should drive large-scale, multidisciplinary, impact-based research to close the knowledge gaps.
Davies warned that action on the ground against antimicrobial resistance will require evidence; research to gather evidence, she added, requires the appropriate policy and funding, which can only be obtained through
political and civil engagement. She remarked that “If we don’t get this right, not only will there be an impact with people dying of infection and that will alter modern medicine, but it will impact global health security and agricultural livelihoods and our environment.”
Davies emphasized that antimicrobial resistance is a complex, intricate problem that is not easily visible and understood by the public. However, the reality is that drug-resistant infections cause nearly one death every 45 seconds around the world—with the young, the old, the immunocompromised, and the pregnant disproportionately affected (Review on Antimicrobial Resistance, 2016). If the tide is not stemmed, the rate will increase to one death every 3 seconds, and 28 million people, mostly in developing countries, will be pushed into extreme poverty by 2050 (World Bank, 2017). With the ability of antimicrobial resistance to contribute to increased mortality and poverty worldwide and to affect the global economy, she added, achieving the UN’s Sustainable Development Goals will require antimicrobial resistance to be addressed.
Despite this need to address antimicrobial resistance, Davies reported that there have been no new classes of antibiotics in routine clinical practice since the 1980s because the market has failed. Not only have companies withdrawn from the market, but also the research environment is barren, she said. Reliance on new drugs is not the complete answer though, reminded Davies, as other efforts such as surveillance and interdisciplinary work, including contributions from economists, are also crucial. With all this said, she also pointed out that more people die worldwide from lack of access to antimicrobials than to resistance, and so handling the tension between lack of access with excess use is critical.
Davies remarked on the push for global action on antimicrobial resistance over the past few years. Repeating what Fukuda mentioned earlier in his presentation, Davies said that significant diplomatic efforts to engage across sectors and countries have helped achieve progress. She particularly highlighted the importance of the 71st session of the UN General Assembly high-level meeting in 2016 that Fukuda alluded to, where heads of state adopted a political declaration calling for coordinated global action—an agreement that had been negotiated among member states under the leadership of the Permanent Representative of Mexico. Several countries, including China, Germany, the Netherlands, Sweden, and the United Kingdom, also played key leadership positions, she added. There was also progress with the G20 in 2017 with a communique to be put forth a few weeks after the workshop by G20 leaders on commitment to combating antimicrobial resistance (G20 Leaders, 2017). Davies said negotiations continue on the diplomatic level.
Davies provided further details on the IACG, which she directs the
work of as one of the three conveners.5 IACG is supported by the tripartite secretariat of FAO, OIE, and WHO, has membership from all UN agencies, brings together experts across difference sectors including the environment, and is cochaired by the WHO director general and the UN deputy secretary-general. She was optimistic that the IACG will serve as a useful mechanism for driving action through the following terms of reference (IACG, 2017):
- Raise awareness and support implementation of major global priorities, tools, and standards for reducing antimicrobial resistance, including WHO’s global action plan and supporting the Sustainable Development Goals.
- Coordinate mapping of actions being taken by UN agencies, other organizations, and key stakeholders toward achieving measurable results, and identify opportunities for collaboration, as well as gaps, redundancies, and duplication.
- Promote, plan, and facilitate collaborative action to align activities so gaps are closed and resources are optimally distributed.
- Explore the feasibility of developing global goals and ambitions related to antimicrobial resistance for UN agencies, component members, and, where appropriate, other stakeholders, for priorities set out in the declaration.
- Regularly report on progress and on IACG meetings and issue a full report to the UN General Assembly at its 73rd session in 2018, through the secretary-general, keeping member states, stakeholders, and the governing bodies of FAO, OIE, and WHO fully apprised of progress.
Davies reported that the IACG’s initial work plan includes aligning with the Sustainable Development Goals and WHO’s global action plan; reviewing work ongoing by FAO, OIE, and WHO; and mapping a framework for action. Making progress on metrics—surveillance, monitoring, and evaluation—is also a priority for Davies. Progress is being made, she noted, with the plans for the Institute of Health Metrics and Evaluation to include antimicrobial resistance into the Global Burden of Disease resource, which provides a tool to quantify health loss from diseases, injuries, and risk factors so health systems can be improved. Furthermore, 90 percent of the world’s population is now covered by national action plans against resistance (WHO, 2017a). However, plans are meaningless without action, Davies noted, and implementing plans will require more funding, which may need more coordination on the national and global levels. Interna-
5 The other two conveners are Junshi Chen and Martha Lutterodt.
tional push funding has increased dramatically since 2014, she said, but more pull funding will be needed for diagnostics and therapeutics.6 Davies concluded her presentation by encouraging the audience to play a key role in the fight against antimicrobial resistance by following infection prevention and control practices, such as handwashing, which can reduce antibiotic consumption.
6 Push incentives, such as research grants, subsidized loans, and tax credits, aim to reduce industry’s costs to help stimulate research and development through the basic research, preclinical, and clinical trial phrases, whereas pull incentives, such as add-on payments, market exclusivity, and intellectual property protections, are provided during the approval process and the post-market period to create viable market demand.
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