With the emergence and spread of antimicrobial resistance (AMR), the already limited arsenal of effective antibiotics has become even smaller, threatening infectious disease management worldwide and putting millions of lives at risk. The threat is greatest for the very young, the very old, and the severely ill.
The toll is already substantial. Of the estimated 7.7 million deaths caused each year by bacterial infections, 4.95 million are associated with drug-resistant bacterial pathogens, and 1.27 million are directly attributable to AMR. And those numbers will only rise if AMR continues to spread, the antibiotics that much of modern medicine relies on become less and less effective, and the world's poorest countries remain unable to access new antibiotics.
But that outcome is not inevitable, according to a new series of papers on AMR and sustainable access to effective antibiotics published last week in The Lancet by an international collection of more than 40 scientists and experts.
Scaling up infection prevention and control strategies, childhood vaccine programs, and access to safe water and hygiene could prevent hundreds of thousands of deaths from resistant infections. Reducing inappropriate antibiotic use in humans and animals, strengthening AMR surveillance, and developing better diagnostics could help preserve current antibiotics. And rethinking antibiotic development could make new antibiotics more sustainable, affordable, and accessible.
All of these goals are achievable with the political will and commitment, the authors argue. And the upcoming United Nations (UN) High-Level Meeting on AMR will provide a "window of opportunity" for countries to start turning the tide.
"For too long, the problem of AMR has been seen as either not urgent or too difficult to solve," the experts wrote in an executive summary of the series. "But neither is true. We need immediate action and the tools to do so are widely available."
Boosting existing interventions could cut AMR deaths
While AMR is a threat to everyone, the first paper in the series suggests those at the beginning and the end of their lives and those with chronic illnesses face the biggest threat. For example, one third of newborn deaths globally are attributable to infections, and half of those are due to sepsis, which is becoming increasingly difficult to treat in low-resource settings because of drug resistance. The authors note that a study conducted in 11 countries found that 18% of babies who had pathogen-positive blood cultures died despite receiving empiric antibiotic therapy.
On the other end of the spectrum, people over 65, especially those with comorbidities and frequent interactions with healthcare, face a rising risk from increasingly resistant healthcare-associated infections. And AMR is also undermining the safety of treatments for people with cancer, chronic lung illnesses, cardiovascular disease, and diabetes.
"Access to effective antibiotics is essential to patients worldwide," series coauthor Iruka Okeke, PhD, of the University of Ibadan in Nigeria, said in a journal press release. "A failure to provide these antibiotics puts us at risk for not meeting the UN sustainable development goals on child survival and healthy aging."
But improving access to effective antibiotics is only part of the solution, according to the second article in the series. In a modeling analysis, a team led by Joseph Lewnard, PhD, of the University of California, Berkeley, estimates that existing infection-prevention methods could prevent as many as 750,000 deaths associated with AMR a year in the low- and middle-income countries (LMICs) that bear the highest burden. That represents roughly 18% of the AMR-associated deaths that occur in LMICs annually.
"Focusing on interventions with demonstrated effectiveness in preventing infections must be at the heart of global action to tackle AMR," Lewnard said in the release. "Preventing infections reduces the use of antibiotics and reduces selection pressure for AMR so that the drugs will work when they are most needed."
The study modeled three specific strategies the authors believe have the greatest potential for reducing the AMR burden in LMICs. The first is aligning infection prevention and control standards in healthcare facilities in LMICs with the current standards in high-income countries, which they estimate could prevent up to 337,000 AMR-associated deaths. Next is achieving universal access to WASH (water, sanitation, and hygiene) services, which could prevent 247,800 AMR-related deaths.
Achieving universal coverage of high-priority pediatric vaccines, such as pneumococcal and rotavirus vaccines, would save an additional 181,500 lives a year by both preventing resistant infections from occurring and reducing antibiotic consumption, according to the analysis.
Lewnard and colleagues say these results can help guide the countries' investments in public health interventions that target AMR.
Expanding access to new antibiotics
While preventing bacterial infections from occurring will play a critical role in the global fight against AMR, a third paper in the series argues that sustained progress against AMR will require more efforts to bolster the pipeline of new, innovative antibiotics, which has been unable to keep pace with AMR, particularly the increase in multidrug and pan-drug–resistant bacterial strains. It will also require a strategy to make new antibiotics accessible to all who need them.
The problems with the antibiotic pipeline have been well-documented. While antibiotic development is challenging, the central issue, the authors of the paper argue, is that the traditional, revenue-driven model of drug development no longer works for antibiotics. Because of the low return on investment, many large pharmaceutical companies are walking away from antibiotic research and development, while smaller companies struggle to stay afloat.
For too long, the problem of AMR has been seen as either not urgent or too difficult to solve....But neither is true.
As a result, few of the candidates in the pipeline are truly innovative drugs. Most, in fact, are offshoots of established antibiotic classes. To fix this problem, the authors say, push and pull incentives will be needed to support companies in the early stages of antibiotic development and to ensure that new antibiotics produce enough revenue for companies to encourage further investment.
But that alone won't solve another critical issue: Even when new antibiotics are approved, they aren't available in most of the LMICs that desperately need them because they aren't registered in those countries. And even when they are available, they're likely to be unaffordable for most of the population.
One solution they suggest is public-private partnerships for antibiotic development and access that are similar to efforts to develop and procure drugs for HIV, malaria, and tuberculosis. These types of models could improve access to antibiotics in LMICs, lower the cost of antibiotic development, and support future investment in antibiotics and novel alternatives.
"Reducing the impact of AMR through pharmaceuticals is not simply a matter of developing new antibiotics," said paper coauthor and One Health Trust Director Ramanan Laxminarayan, PhD, MPH. "Unless access and affordability are guaranteed, the vast number of deaths from resistant bacterial infections will continue unabated."
Laxminarayan and colleagues also call for more investment and innovation in diagnostics to ensure that existing and new antibiotics are used appropriately, higher uptake of approved bacterial vaccines, and funding for new vaccines that could address both bacterial pathogens and viral illnesses that drive antibiotic use.
Global targets
In the fourth article in the series, Laxminarayan and his coauthors propose three "ambitious yet achievable" global targets for 2030 that they believe should be included in the political declaration that emerges from the September 2024 UN High-Level Meeting on AMR. While the 2016 UN meeting heightened awareness of AMR among world leaders and led to the creation of national AMR action plans, critics have often cited the lack of actionable targets as a missed opportunity.
"The absence of international accountability for AMR partially relates to an absence of agreed targets," they wrote. "Without targets and subsequent monitoring and evaluation, tracking progress is difficult."
The goals, dubbed "10-20-30 by 2030," call for a 10% reduction in mortality in AMR deaths, a 20% global reduction in inappropriate human antibiotic use, and a 30% reduction in inappropriate animal antibiotic use. In addition, the authors recommend the establishment of an independent scientific body—the Independent Panel on Antimicrobial Access and Resistance—to ensure accountability and scientific consensus and call for increased funding for infection-prevention programs in human health and food production in LMICs.
Unless access and affordability are guaranteed, the vast number of deaths from resistant bacterial infections will continue unabated.
