[Updated Version - 05-02-2024]
Tackling Antimicrobial Resistance: What is the global strategy missing?
The Global Context: One of the big events in the global health policy in the coming year is the United Nations High Level Meeting on Antimicrobial Resistance scheduled for September 2024 [1]. There is undeniable merit in categorizing antimicrobial resistance as one of the top-ten global threats, and the proposed breadth and urgency of action are highly required.
“Worldwide AMR is estimated as directly causing 1.27 million deaths and contributing to a further 4.9 million deaths per year, making antibiotic-resistant infections more deadly than HIV/AIDS or malaria. But AMR is also a serious threat to food security (SDG2) because it increases the loss of animal lives due to untreatable infections and raises the cost of animal health care. …. The economic toll of AMR is expected to result in a GDP drop of at least $3.4 trillion annually by 2030 and push 24 million more people into extreme poverty (SDG1).” 1–3. But progress has been slow with only 27% of nations report effective implementation of the plan.
Though a world-wide threat, its adverse consequences are far worse in Low- and Middle-Income Countries( LMICs) and within this category, India has the highest burden of the problem 4. The complexities of antimicrobial resistance (AMR) in LMICs stem from a variety of factors, including the practices of healthcare professionals, patient behaviours regarding antimicrobial usage, and the supply chains of antimicrobials within the population. Contributing elements may encompass inappropriate prescription practices, insufficient patient education, limited access to diagnostic facilities, unauthorized sales of antimicrobials, inadequacies in drug regulatory mechanisms, and the non-human use of antimicrobials, such as in animal products 5.
In India specifically, several factors such as the- inadequate public health systems, suboptimal hospital infection control, elevated rates of infectious diseases, and unregulated clinical practices, often conducted by providers with limited training and qualifications, are contributing to the rising prevalence of resistant pathogens. This situation is amplifying the burden of untreatable neonatal sepsis and healthcare-associated infections. Though there is a policy in place in India for addressing AMR, reports show limited compliance with the guidelines 6,7
[1] This High Level meeting, is convening seven years after the first such meeting held in 2016 and which meeting endorsed the WHO Global Action Plan on Antimicrobial Resistance adopted in the 68th World Health Assembly in year 2015. Further in 2018, under the leadership of the UN, a Quadripartite partnership of WHO, The Food and Agriculture Organization (FAO), the United Nations Environment Programme (UNEP) and the World Organisation for Animal Health (WOAH) endorsed the global action plan and agreed on multisectoral actions for its implementation. This year begins with the Executive Board of the WHO endorsing a report made and adopting a political declaration, sponsored by 27 nations, on this issue. In India, which already had a National Plan of Action for 2017 to 2022 is also getting ready to adopt its next action plan.
Proposed Strategies- Global and National
This Report to the EB proposed three strategies for a comprehensive public health response to antimicrobial resistance in the human health sector. The first is the prevention of all infections that give rise to the use of antibiotics, noting that viral and other infections also contribute to inappropriate antibiotic use. The second strategic priority is universal access to quality diagnosis and appropriate treatment of infections. The third priority is strategic information and innovation – notably surveillance of both antimicrobial resistance and antimicrobial consumption/use; the development of new vaccines, diagnostics and antimicrobial agents; and measures to make these accessible and affordable. There is a foot note that adds that this formulation of strategic and operational priorities is tentative and would be finalized after global consultation.
However, though most statements in the draft report and draft decision are welcome, these are not sufficient. Part of the reason for this is the lack of a critical review on the lack of progress in the last seven years since the Global action plan was adapted. Reviewing this lack of progress, the PHM had posted its critical observations and recommendations 8 .
This article builds on that to influence the deliberations in the scheduled UN meeting on this issue.
Reducing Infectious Disease in the Community
The first of the three strategies calls for ensuring that all that everyone has access to safe water, sanitation, hygiene, and waste disposal, and these largely relate to water-borne illness. It should have also called for ensuring that there is protection against other adverse social and environmental determinants of ill health- like air pollution, poor nutrition, poor housing and over-crowded settlements, safety standards in public buildings and open spaces and poor working conditions all of which could promote respiratory infections. Neither the report nor the resolution goes beyond an abstract understanding of behaviour change, without understanding the political economy that creates the conditions for such behaviours. While measures like WASH are necessary, they are far from sufficient to make a difference. Since the poorer and marginalised sections are the main victims of poor hygiene, the emphasis on individual behaviour changes amounts to victim blaming and this only adds insult to injury and compounds the problem. The UN Assembly should give a call for countries to enact and implement public health laws which are rights oriented. “Public health law enables a nuanced understanding of the role of government in creating the conditions for people to be healthy, the reasonable limits that governments may place on personal freedom to promote the health of the population” 9.
The Public Health Laws in place in many nations were made under colonial rule to protect the enclaves of the privileged, and these make the citizen accountable to the state with a reliance on policing and coercion for enforcement. The need is for public health legislations that can enforce the rights of the citizen on the state to ensure that access to safe water, sanitation, and hygiene measures are delivered as an entitlement through public services. Most countries which do have such a law, provide for local self-government institutions viz municipalities and their rural equivalents- as their duty bearers. This is welcome. But local-self governments are not provided with the financial powers, the transfers of technology and other capacities required to play their role. Prevention of cross-infections in the facility is of course important and the report emphasizes, but here too it is not a stand-alone intervention but one which is integrated with quality-of-care improvements. While the first strategy is appreciated, as currently outlined, it overly focuses on health facilities and lacks substantial content regarding community-acquired infections, making it less likely to have a significant impact
The Paradox: Problems of Access and of Overuse
The second strategy addressed the misuse and the overuse of antibiotics as the main driver of antimicrobial resistance. The strategy correctly notes that while misuse and overuse are a problem, there are in parallel persistent problems of access to essential antibiotics when required. For this the WHOs AWaRE approach is a good start. This approach categorises medicines into categories of Access: which are first line antibiotics which should be easy to access and universal and b) Watch- where antibiotic resistance is likely to develop and which we need to restrict to only circumstances where the first line does not work and Reserve- which antibiotics must be used very sparingly and only when there is AMR to other antibiotics. In practice, this has been very difficult to implement in many LMICs, and drugs on the second and even third category or often used as first line, and even as preventives, where they have no role at all.
Commercially conditioned provider and patient behaviours
Much of inappropriate use of antibiotics is because of commercial pressures and the nexus it has with professional behaviours. These pressures lead to shaping public demand in favour of inappropriate use and leads to a legitimizing vicious cycle 10. This report addresses this entire problem as an issue of consumer and provider behaviour and again completely leaves out the political economy considerations which are the main drivers. These are:
- As related to commercial marketing: There is aggressive and often unethical marketing of pharmaceuticals, with inducements and incentives offered to prescribe higher cost antibiotics of the higher two categories. The use of brand names to provide an irrational marketing and pricing advantage and the failure to ensure generic names. Antibiotics are often sold as irrational combinations, often to avoid regulatory price controls or for branding and marketing purposes. Antibiotics are also promoted and used by informal care providers who have no training, and have picked up these practices from the market. And most important, updated unbiased, scientific prescription information on newer antibiotics is not available to prescribing physicians. The relationship of professional associations to such marketing is mixed with many falling preys to the inducements and only few who are able to stand above it.
- As related to quality assurance: It is much easier to ensure quality when it is part of public procurement, it is almost impossible to assure the same in private retail markets. So often sub-standard antibiotics are available in many LMIC markets.
Competitive pressures and health-seeking culture in the private sector: there are much greater pressures on private providers to prescribe a greater number of antibiotics with greater power, and promising more immediate relief, so as to have a competitive advantage with other providers in the market.
- Patients’ behaviour toward irrational antibiotic use is not solely a result of providers’ low education. Adequate patient education, also indicative of high-quality care, enhances responsive healthcare and is fundamentally a matter of patients’ rights. In the context where, in 18 countries representing approximately 50% of the global population, patients spend 5 minutes or less with their primary care physicians, the issue of patient engagement to build an understanding about the rational use of antibiotics remains a major concern 11. Average consultation time serves as a recognized quality measure and is endorsed by both the WHO and the International Network for the Rational Use of Drugs (INRUD) for enabling the safe and cost-effective utilization of drugs12. We propose that the strategy should explicitly include average consultation time, as a key systems challenge and as a key metric to assess rational use of antibiotics, as part of the surveillance of antimicrobial consumption to guide patient care and action on antimicrobial resistance.
All these marketing related distortions of ethical and scientific healthcare are not limited to antibiotics, but with antibiotics they contribute in a major way to the misuse of antibiotics. The strategy should therefore call for strong regime of marketing regulation, accompanied by provision of good quality information and proactive promotion of better antibiotic choices. This would have to be part of a better regulatory regime for private sector care in LMICs. Especially in primary health care, but in all levels of health care, one principle of organizing health services must be that clinical decision making is not subject to market pressures. This can be best assured in public provisioning of services or in designing contracts with private providers, which adhere to this principle.
Microbiological Capacity in health systems
When it comes to stewardship, the first requirement is a significant increase in microbiological capacity- laboratories, professionals, technicians. There is a need to have such capacity even at the district level and to develop technologies that enable this. This is a requirement for surveillance too. It is also important to call for the use of information from microbiology surveillances in a real time basis for local and regional antibiotic stewardship. There is a danger that accelerating the consumption of microbiological and genomic diagnostics for every individual infection episode, would increase costs of care without necessarily improving antibiotic decisions. There is a need for providers to be guided by patterns of antibiotic sensitivity in each region and reducing the necessity for testing. The strategy should therefore call for public provision of microbiological guidance including affordable rate controlled or free testing services to all patients irrespective of choice of provider. It should also call for local availability and use of information from ongoing microbial surveillance.
Misuse in the Animal/Veterinary Sector
This report and the draft decision are surprisingly silent on the misuse of antibiotics in the animal/veterinary sectors, though it is well known that much of the antibiotic resistance that arises even in human infection is from the commercial practices in the animal sector. India is the fourth largest user of antibiotics in animal feed, the others being China USA and Brazil. At the current rate of change India could become the major consumer of antibiotics in animal husbandry. There are also high levels of sub-standard antibiotics in this sector 13,14 (Perhaps this silence is because, this issue is addressed in the sector-wide strategies of the other Quadripartite partners. However, without providing cross-references and linkages to the relevant documents and showing the points of convergence, this strategy is incomplete. The strategy should call for banning the use of antibiotics for preventive purposes and growth promotion in rearing animals for food, better microbial surveillance and feedbacks to farmers and veterinarians to guide antibiotic choice, and restriction of some antibiotics for use in some sectors. Even greater silence exists in relation to antibiotic leakage into the environment.
Need for an alternative innovation regime
This commercial basis of the pharmaceutical sector also relates to the current challenges of innovation which is the third strategy proposed in this report. The current innovation and knowledge regime is bad for all essential medicines of public health importance, but when it comes to anti-biotics it is particularly terrible. By definition third and fourth generation antibiotics have to have very restricted use- which means a very limited market size and very high price mark-ups. It is not possible to create an intellectual property regime and a financing model just for newer antibiotics. Public financing of antibiotic research would help, but without control over patents and distribution we will see the same outcome as we saw with Covid vaccines- a huge profit to big pharma with high inequities in access, despite the public finance. A strategy to develop a more effective innovation regime should a) delink the price of innovation and development from the price of marketing the drug- the latter reflecting only manufacturing costs and b) where public financing is involved, mandate a public acquisition of IPRs and mandatory licensing of multiple generic manufacturers to undertake production including where possible public sector manufacture.
In summary though there are many welcome measures in these strategies it is far too incomplete to succeed. In our regions there is a local saying: “like jumping across a well and managing to cross only nine-tenth across it.” Good try, but you still fall in.
Call to the UN’s High-Level Meeting
It is important therefore for member-states and civil society and public health professions to ask that, in addition to its current articulation of three strategies, the Political Declaration in the United Nations High Level Meeting on Antimicrobial resistance includes the following:
- A call to countries to enact and implement public health legislations that can enforce the rights of the citizen on the state to ensure that access to safe water, sanitation, and hygiene measures is delivered as an entitlement through public services. This would need to go along with local-self-governments being provided with the financial powers, the transfers of technology and other capacities required to play their role.
- A call for strong regime of antibiotic marketing regulation, accompanied by provision of good quality information and proactive promotion of better antibiotic choices. This would have to be part of a better regulatory regime for private sector care in LMICs. Especially in primary health care, but in all levels of health care, one principle of organizing health services must be that clinical decision making is not subject to market pressures. This can be best assured by public provisioning of services and in designing contracts with private providers, which adhere to this principle.
- Ensuring public provision of microbiological guidance including affordable rate controlled or free testing services to all patients irrespective of choice of provider. It should also call for local availability and use of information from ongoing microbial surveillance.
- Banning the use of antibiotics for preventive purposes and growth promotion in rearing animals for food, better microbial surveillance and feedbacks to farmers and veterinarians to guide antibiotic choice, and restriction of some antibiotics for use in some sectors
- Ensure that the UN high-level meeting and political declaration is a call of the quadripartite alliance and not only of the human health sector.
A more effective innovation regime for antibiotics which should a) delink the price of innovation and development from the price of marketing the drug- the latter reflecting only manufacturing costs and b) where public financing is involved, mandate a public acquisition of IPRs and mandatory licensing of multiple generic manufacturers to undertake production including where possible public sector manufacture.
Authors: T. Sundararaman, Shalini Singh
References and for further reading:
- EB154_PHM_IntegratedItemCommentariesFinal_240118R.pdf. Accessed February 4, 2024. https://who-track.phmovement.org/sites/default/files/2024-01/EB154_PHM_IntegratedItemCommentariesFinal_240118R.pdf
- EB 154th session W. Antimicrobial resistance: accelerating national and global responses EB154/CONF./7 154th session 23 January 2024.
- EB 154th session WD 2023. Antimicrobial resistance: accelerating national and global responses, WHO strategic and operational priorities to address drug-resistant bacterial infections in the human health sector, 2025–2035-Report by Director General.
- Moss M. Charting the Course for the AMR Agenda in 2024. unfoundation.org. Published November 28, 2023. Accessed February 4, 2024. https://unfoundation.org/what-we-do/issues/global-health/the-amr-agenda-in-2024/
- Laxminarayan R, Chaudhury RR. Antibiotic Resistance in India: Drivers and Opportunities for Action. PLOS Med. 2016;13(3):e1001974. doi:10.1371/journal.pmed.1001974
- Ayukekbong JA, Ntemgwa M, Atabe AN. The threat of antimicrobial resistance in developing countries: causes and control strategies. Antimicrob Resist Infect Control. 2017;6(1):47. doi:10.1186/s13756-017-0208-x
- Ranjalkar J, Chandy SJ. India’s National Action Plan for antimicrobial resistance – An overview of the context, status, and way ahead. J Fam Med Prim Care. 2019;8(6):1828-1834. doi:10.4103/jfmpc.jfmpc_275_19