Introduction

Each year, an estimated 7.7 million deaths are caused by bacterial infections – 4.95 million of these are associated with bacterial pathogens resistant to the antibiotics available to treat them (1). Globally, antimicrobial resistance (AMR) is the third leading cause of death after ischemic heart disease and stroke (1), posing a significant and growing threat to public health. 

AMR presents a significant challenge to the sustainability and effectiveness of public health responses to communicable diseases and epidemics. Despite the continuous progress made, this crisis is escalating at a rate that surpasses the current response - and the cost of AMR is high. 

Urgent action is needed to address this pressing issue. The world is as yet unprepared for the predicted 20% increase in mortality resulting from AMR between now and 2050 (2,3).

This emerging global health crisis transects sectors and multiple dimensions, requiring a collaborative approach. To combat this formidable public health threat, we need to work together across sectors. 

Cross-sectorial collaboration is not just a strategy, it's a necessity.

The Lancet Series on AMR | A Foundation for Action

There are very few issues in global health with such consensus and advocacy yet so little concrete action as AMR (13). 

In May 2024, the Lancet launched a global series on AMR, the need for sustainable access to effective antibiotics, and illuminating the havoc AMR is reeking on global health.

In conjunction with the upcoming United Nations (UN) General Assembly, which includes a high-level meeting on AMR, this seminal work is just one vital step forward in the battle against AMR. 

The series, authored by leading experts and comprised of an executive summary, four research papers, and a commentary, focuses on interventions and investments that can guide decision-making to achieve sustainable access to effective antibiotics and accelerate progress in addressing AMR (1,7-11). 

Key Recommendations from the Lancet Series

This comprehensive roadmap presents an in-depth analysis of the emerging global AMR crisis, offering data-driven insights and evidence-based recommendations. 

It outlines specific, actionable steps to combat AMR, including preventing infections, optimising antibiotic use, developing new antibiotics, and investing in AMR research and surveillance (1,7-11). 

The new Series provides robust evidence on the effects of expanding methods to prevent infections, such as access to safe drinking water, adequate sanitation, vaccination, and infection and prevention control in health-care facilities. 

It concludes by proposing concrete, measurable goals for reducing AMR mortality and antibiotic use by 2030.

Some of the key recommendations include:

• Prevention: Investing in improved sanitation, hygiene, and vaccination programmes to prevent infections.

• Antibiotic Stewardship: Optimising antibiotic use in human and animal health to reduce the emergence of resistant bacteria.

• Research and Development: Increasing investment in research to discover new antibiotics and develop rapid diagnostic tools.

• Surveillance: Strengthening surveillance systems to track the spread of antimicrobial resistance and inform public health interventions. 

• One Health Approach: Recognising the interconnectedness of human, animal, and environmental health in addressing AMR.  

Essentially, the Lancet Series has provided a robust evidence base for the UN meeting, which is expected to translate these recommendations into concrete actions and commitments at the global level.

As Dr. Ramanan Laxminarayan (President of the One Health Trust) said ¹³ in his opening remarks at the launch of the Lancet Series:

"For too long, AMR has been seen as either not urgent or too difficult to solve. But neither is true.

We need immediate action."

The UN General Assembly | A Global Commitment

The Lancet Series directly informs and influences the upcoming UN High-level Meeting on AMR in September 2024.

The last high-level UN meeting on AMR occurred at their General Assembly in 2016 and laid the groundwork for tackling the AMR crisis.

The upcoming high-level meeting is a crucial platform to urgently address the drivers of morbidity and mortality due to drug-resistant infections and highlight excellence in antibiotic stewardship.

This meeting is an essential opportunity for world leaders to collectively address AMR's looming threat to global health and food security and achieve the 2030 Sustainable Development Goals (12). 

Goals of the UN High-Level Meeting

This meeting aims to galvanise global action and secure high-level political commitment to address the crisis. 

Key goals include:

• Global Action Plan: Developing a comprehensive global action plan to combat AMR.

• Increased Investment: Mobilising additional financial resources for AMR research, development, and implementation.

• Stewardship and Access: Improving antibiotic stewardship and ensuring equitable access to essential medicines. 

• Surveillance and Data: Strengthening surveillance systems and data sharing to inform decision-making. 

• One Health Approach: Promoting a One Health approach to address AMR accross human, animal, and environmental sectors. 

   

Antimicrobial Stewardship (ABS) - The REVERSE Project

Improving antibiotic stewardship is a critical component of both the Lancet recommendations and the UNGA goals (1,7-12). Research projects provide valuable data, inform practice, and offer innovative strategies.

One such research project is REVERSE -pREVention and management tools for rEducing antibiotic Resistance in high prevalence SEttings. This mixed-method approach combines quantitative research with implementation science and cost analysis to answer questions about the real-life effectiveness of infection prevention and control (IPC) programmes in combination with antibiotic stewardship on healthcare-associated infections due to multidrug-resistant microorganisms. 

With its collaborative nature, the project will offer expert implementation support to the participating hospitals and will additionally study the effectiveness of this external support in a hybrid implementation-effectiveness trial. REVERSE will also develop a novel health-economic framework that allows for incorporating the effect of changes in the use of a range of antibiotics on antibiotic-resistant infections and estimating long-term population effects to integrate both into cost-effectiveness analyses. 

It will conclude the effectiveness and applicability of prevention strategies in lower-resource settings by cross-checking its programmes with activities in low- and middle-income countries.

Intersection

The recommendations from the Lancet Series, the ongoing research in the REVERSE project (and others like it), and the UN GA’s goals for AMR intersect. 

Our goals align.

The Lancet series proposes what they describe as ambitious yet achievable global targets – the ‘10-20-30 by 2030’ goals. 

Target 1: A 10% reduction in mortality from AMR

IPC measures are vital here. Scaling up existing services and implementing new innovations must occur to reduce infection rates and AMR-associated morbidity and mortality. 

Within the REVERSE project, IPC is a central focal point being tackled through intervention programmes, new training tools, education, and more. Work package three focuses on this programme within REVERSE. They will determine the effects of bespoke protocols designed to augment basic and enhanced IPC measures to decrease the incidence density of healthcare-associated CRE, CRPA and CRAB infections, as well as their prevalence in repetitive screening surveys.

Target 2: A 20% reduction in appropriate human antibiotic use

The overuse and misuse of antibiotics play a massive role in AMR, and improved antibiotic stewardship is critical. We must address education, training, availability, and accessibility to improve antibiotic usage. This applies to healthcare professionals and all stakeholders, including the general public.

A key component of the REVERSE project is focussed on antibiotic stewardship, actively visiting sites, meeting and training ABS teams and ward champions, and developing and implementing new interventions—designed as a cohesive approach to improving overall antibiotic prescribing. 

Target 3: A 30% reduction in inappropriate animal antibiotic use

AMR is a complex problem requiring coordinated sector-specific actions in the human health, food production, animal, and environmental arenas. A One Health approach is vital to significantly impact AMR across the board. As humans, our health is intertwined with animals and our environment. Approximately 18% of AMR-related burden can be averted using WASH (Water, Sanitation and Hygiene), vaccines, and better IPC (7).

The One Health approach to preventing and controlling AMR brings stakeholders from relevant sectors together to communicate and collaborate on the design, implementation, and monitoring of programmes, policies, legislation, and research to mitigate AMR and attain better health and economic outcomes (7,9-10). 

Conclusion 

If we are to tackle AMR and rid ourselves of this burden, it is clear that the problem is complex and intersecting and that continued research, policy implementation, and global cooperation are vital. 

The Lancet Series on Antimicrobial Resistance is a pivotal cornerstone in our global fight against this formidable threat. Its comprehensive analysis and far-reaching recommendations have underscored the urgency of the crisis and illuminated the road forward. ABS is an indispensable strategy in this battle, offering a multifaceted approach to preserve the efficacy of existing antibiotics.

The upcoming UN General Assembly presents a critical juncture for global action on AMR. By leveraging insights from the Lancet Series and advancements in AMR research, world leaders have an unprecedented opportunity to forge a united front against this crisis. The work that is done in projects like REVERSE is now more important than ever. A concerted effort to implement evidence-based strategies, invest in research and development, and strengthen surveillance systems is imperative.

Ultimately, the success of combatting AMR depends on sustained commitment, collaboration, and innovation. Only through a collective, multi-sectoral approach can we safeguard our health and well-being for generations to come.

We look forward to a concise and action-oriented political declaration from the UN GA with a shared vision, including the consideration of measurable targets and objectives, agreed in advance by consensus through intergovernmental negotiations, to be submitted by the President of the General Assembly for adoption by the Assembly.

References

1. Antimicrobial resistance: an agenda for all. Lancet. 2024; 403:10442. 
2. Murray CJ, Ikuta KS, Sharara F, et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022; 399: 629-655.
3. Tang KWK, Millar BC, Moore JE. Antimicrobial Resistance. Br J Biomed Sci. 2023 Jun 28;80:11387. doi: 10.3389/bjbs.2023.11387. PMID: 37448857; PMCID: PMC10336207.
4. Ilkuta KS, Swetschinski LR, Aguilar GR, et al. Global mortaility assosicated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2022; 400: 221-48. 
5. Murray CJ, Ikuta KS, Sharara F, et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022; 399: 629-55. 
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7. Lewnard, JA, Charani, Gleason, AE, et al. Burden of bacterial antimicrobial resistance in low-income and middle-income countries avertible by existing interventions: an evidence review and modelling analysis. Lancet. 2024; 403:(10442): 2439-2454.
8. Laxminarayan, R, Impalli, I, Rangarajan, R, et al. Expanding antibiotic, vaccine, and diagnostics development and access to tackle antimicrobial resistance. Lancet. 2024; 403:(10443): 2534-2550.
9. Shrestha J, Zahra F, Cannady PJ. Antimicrobial Stewardship. [Updated 2023 Jun 20]. In: StatPears [Internet]. Treasure Island (FL): StatPears Publishing;2024 Jan.
10. Fatokun O, Selvaraja M, Anuar H, et al. Antimicrobial resistance at the human–animal–environment interface: A focus on antimicrobial-resistant Escherichia coli transmission dynamics, clinical implications, and future directions. Int J One Health. 2024;10(2):161-71. doi: 10.14202/IJOH.2024.161-171.
11. Okeke IN, de Kraker MEA, Van Boeckel TP, et al. The scope of the antimicrobial resistance challenge. Lancet. 2024;403(10442):2426-38.
12. Mendelson M, Lewnard J, Sharland M, et al. Ensuring progress on sustainable access to effective antibiotics at the 2024 UN General Assembly: a target-based approach. Lancet. 2024;403(10443):2551-64.
13. One Health Trust. Launch of The 2024 Lancet Series on Antimicrobial Resistance. 2024. May 23. Available from: https://youtu.be/xboBz-wdqVs.