The Global Threat of Antimicrobial Resistance
Nearly 90 years ago, the antibiotics era began when a chance discovery by Alexander Fleming, a professor of bacteriology at St. Mary’s Hospital in London, spawned a series of laboratory experiments that culminated in the isolation of penicillin from “mold juice.” So began a nearly 20-year global effort to manufacture pure penicillin on a commercial level, culminating in this lifesaving wonder drug’s first wide use by Allied forces during the final year of World War II.
In the years after the war, the challenge was how to increase supply and how to manufacture the medicine on a large scale while initiating demand: helping the drug enter routine use in hospitals around the world so that its remarkable benefits could be realized by all.
Today, we face a very different set of supply and demand problems; in fact, just the opposite of where we started. With dozens of antibiotics now readily available and access to them routine (and sometimes even taken for granted) by so much of the world’s population, we have too much demand. Around the globe, people are consuming antibiotics in ever-greater quantities, often in unnecessary ways. That, unfortunately, is speeding up the pace at which bacteria develop resistance to the antibiotics used to treat them, and progressively undermining the effectiveness of the drugs. Antimicrobial use in the agricultural sector deepens this challenge, driving the emergence of these drug-resistant bacteria. And on the supply side, we face the problem of too few companies developing new drugs to replace those that we are losing to rising resistance.
According to the World Health Organization (WHO), resistance to antibiotics and other types of antimicrobials is growing and represents the single greatest challenge in infectious diseases today. The WHO reported nearly half a million new cases of multidrug-resistant tuberculosis across 100 countries in 2013, amounting to more than 20 percent of previously treatable tuberculosis cases now being resistant to multiple drugs. In the United States, the Centers for Disease Control and Prevention estimates that each year, at least 2 million people become infected with bacteria that are resistant to antibiotics, and at least 23,000 of them die. This inflicts a direct cost of $20 billion on the U.S. health care system. In the agricultural sector, U.S. Food and Drug Administration sales data showed that drugmakers sold more than 20 million pounds of medically important antibiotics for use in food-producing animals in 2014—23 percent more than in 2009—the most ever reported and more than twice the amount of antibiotics sold to treat people.
This is a global health crisis that knows no borders. Left unchecked, antimicrobial resistance (AMR) will touch all people, regardless of their nationality or their country’s level of development. It will dangerously undermine health care as we know it, making common procedures such as cancer chemotherapy or cesarean section births—which depend on effective antibiotics to reduce their risks—far more dangerous than they are today. Indeed, by 2050, 10 million people a year could be dying as a result of AMR, up from around 700,000 today, with China and India each being home to about 1 million affected patients. And by then, an estimated $100 trillion in global GDP will have been lost.
Just as infections travel with the people who carry them, so does resistance, so solving AMR is a shared responsibility. AMR is one of the biggest health threats facing the world, but it is not beyond the world’s ability to meet and conquer it, both economically and scientifically. The global community must act together, and quickly, to address the problem.
In 2014, United Kingdom Prime Minister David Cameron asked me to look at these problems from the perspective of a global economist, and to recommend how the international community can act against this growing threat. After more than 18 months spent immersed in this fascinating topic, my independent Review on Antimicrobial Resistance recently published its final report, which identified several steps that should be taken to prevent the worst effects of AMR.
Global Leaders Must Act
In economic theory, the “tragedy of the commons” is used to describe systems in which individuals act in their own interest instead of acting to help the common good. This theory is often cited for global challenges such as climate change to illustrate the difficulty in motivating individuals to sacrifice—for example, use public transport even if it’s less convenient—in favor of a future and shared objective: reducing air pollution and carbon dioxide emissions. AMR is another issue that can be seen through this lens. Individual interest is generally to continue consuming antimicrobials at the present rates, while the future goal is to reduce demand overall to weaken resistance. Likewise for the supply side of AMR, one company’s motivation may be to invest resources in developing a more lucrative drug for other purposes, while the global need—and that of the pharmaceutical industry—is to have a robust and sustainable supply of new antibiotics, which tend to garner fewer profits and yet are the bedrock upon which so much of modern medicine depends. The way to overcome the tragedy of the commons—in theory and by example—is to achieve cooperation by acknowledging mutual goals and gains and instituting policies or regulations to support targeted collaboration. That is what is needed today.
There are three upcoming opportunities for global leaders to address AMR:
First, the most natural set of countries to initiate cooperation on AMR is the Group of 20, or G-20, which consists of developed nations as well as emerging economies such as South Africa, Brazil, India, and Turkey. The greatest responsibility for action lies with the G-20 because these countries experience the most drug-resistant infections and can do the most to solve the problem.
The best opportunity for this group to make significant policy progress is when the G-20 meets in September in Hangzhou, China. As the host nation and G-20 chair for 2016, China can and should unify G-20 governments on this issue. This has as much to do with national interest as global leadership. The Review on Antimicrobial Resistance’s prediction that as many as 1 million people a year could die because of AMR by 2050 would have a cumulative economic cost of $20 trillion—equivalent to two years of current Chinese output. And other emerging economic powerhouses—including the rest of the countries known as the BRICs (Brazil, Russia, and India, in addition to China)—face steeper climbs to combat AMR because of the rapid growth in demand for antimicrobial drugs. For instance, the BRICs and South Africa accounted for three-quarters of the growth in antibiotic consumption between 2000 and 2010. Given that much of this growth in demand is linked to higher national incomes, the emerging global middle class, and better access to health care, we can project that demand will only increase as more of the emerging world increases its economic wealth and food consumption. Therefore, action by China and its BRICs partners, and the whole of the G-20, promises leadership by example for the rest of the world, which must also engage in sustainable steps to tackle AMR to help reduce our profligate use of these drugs.
Resistance to antibiotics and other types of antimicrobials is growing and represents the single greatest challenge in infectious diseases today.
Second, September also marks the annual meeting of the United Nations General Assembly, which for the first time has AMR on its agenda. At that gathering, global leaders should address AMR by taking the first steps toward concrete commitments that involve the human and animal sectors in parallel, and identifying ways in which the poorest nations can be supported in that effort. The attention to this issue by the U.N. leadership would be immensely important and powerful. It is through the U.N. that the focus and plans of global leaders turn to action, particularly with a broader base of representatives that include developing nations and civil society. So what is needed most from the U.N. is a clear and compelling call to action that is based on the collaboration of all nations and civil society, taking AMR action steps ranging from communiqués to country-level changes.
The third global leadership opportunity resides with the World Health Organization. The organization’s work on surveilling and strengthening the capacity of low-income countries to address the challenges of AMR has been critical to progress. Specifically, its proposed Global Antimicrobial Surveillance System is an encouraging step in the direction of a much-needed global network for surveillance of drug resistance.
Beyond global leadership forums, all of us as individuals can take action at the personal, business, and community level. These steps include the very basic—such as better hand-washing and sanitation to reduce the spread of infections—as well as more sophisticated actions such as the development and adoption of technologies to improve the way we diagnose infections and prescribe antimicrobial drugs.
What follows is an AMR action plan that can align the global community on a set of core steps.
A Plan for Action
Supporting antibiotic development
Currently, the most significant supply-side challenge is the mismatch between what we know the world needs in terms of new drug availability and development to defeat rising resistance, and the size and quality of the delivery pipeline. With drug development taking up to 15 years, we need to boost the development of new antibiotic drugs now rather than waiting for a more intense crisis.
The main reason for the mismatch is that the commercial return for a new antibiotic is uncertain until resistance has emerged against a previous generation of drugs. In other medical fields, a new drug is meant to significantly improve on previous ones and so will become the standard first choice for patients after it comes to market. That is often not true for a new antibiotic: Except for patients with infections that are resistant to previous generations of drugs, a new antibiotic is probably no better than any existing and cheap generic product on the market. By the time that new antibiotic becomes the standard first line of care, it might be near or beyond its patent life. This means that the company that developed it will struggle to generate sufficient revenue to recoup its development costs.
Three interventions are needed to remedy this: First, create a more predictable market for antibiotics to sustain commercial investment in research and development. Where necessary, change how antibiotic developers are rewarded to ensure more predictable financial compensation for developers of critically needed new drugs, support conservation efforts, and ensure good value and equitable access for purchasers. Key to this is breaking the connection between a new antibiotic’s profitability and its volume of sales—thereby eliminating the commercial uncertainty that hinders drug companies’ investments in antibiotic discovery and the imperative that they sell new antibiotics in large quantities, which contributes to the development and spread of resistance. I have proposed a new global system of “market entry rewards”: payments of $1 billion or more to the successful developers of antibiotics that meet our most pressing unmet needs. For recipients to receive the rewards, they would have to commit to global affordable access to their product and support for improving the appropriate use of antimicrobials.
Second, by creating a more attractive commercial market for antibiotics, we would develop an environment that encourages investment in the earlier stages of the pipeline to tackle AMR. But for now, a concerted effort is needed to overcome years of underinvestment in early-stage antibiotic discovery by companies and governments alike, in a way that will prime the drug development pipeline. Specifically, I have proposed establishment of a global AMR innovation fund of about $2 billion over five years to boost funding for “blue sky” research into drugs and diagnostics and help more good ideas get off the ground. This money could be found within current government budgets or even more easily within the funds that the pharmaceutical industry spends each year on other initiatives.
Third, we must support efficient drug development through centralized public platforms for clinical trials, better sharing of information at early stages, and regulatory harmonization when they do not endanger patient safety. These interventions would have the potential to make the discovery of new antibiotics faster and more efficient.
We must also consider the role of vaccines, which have the power to fight fast-moving epidemics but can also protect us against the more predictable threat of drug resistance. Vaccines offer a unique opportunity over time to reduce the number of infections that require medication. Yet vaccine development also takes a long time, often more than 10 years, and requires strategic investment and significant research and development. Here, too, we need to consider interventions that might include advance market commitments and market-entry rewards to kick-start development.
We need to boost the development of new antibiotic drugs now rather than waiting for a more intense crisis.
The demand side of AMR has two challenges: antibiotics prescribed to patients who do not need them and a lack of the drugs for those who do. A key solution is to improve diagnosis of medical issues to reduce unnecessary use.
Consider the patient who visits a doctor today for treatment of respiratory problems. The examination of the patient for this type of illness remains essentially unchanged from the days when Fleming discovered penicillin. An antibiotic may be prescribed, as is often the case based on recent research, but the patient may have a condition such as a viral infection for which antibiotics aren’t effective. A new study by the CDC and The Pew Charitable Trusts focused on such interventions in the U.S. and found that this type of unnecessary antibiotic usage amounted to an estimated 47 million courses of antibiotics wasted in one year.
Another issue arises when patients are given powerful antibiotics that should ideally be kept in reserve in case an infection is caused by a drug-resistant strain that would not be cured by older medicines. When such “last line” drugs are given on an initial basis to many patients, cases of multidrug-resistant infections increase, as does the risk that untreatable cases will emerge.
Improved technology permits us to change this pattern. Rapid point-of-care diagnostic tools for bacterial infections, which allow doctors to identify the nature of an infection in minutes instead of hours or days, have the potential to transform diagnosis and treatment from an empirical process to one of precision. Furthermore, technological advances in computer learning and artificial intelligence may be able to help scientists bend the curve of our current diagnostic boundaries to analyze and interpret data faster and more effectively to support better clinical decisions in real time.
Although the precise quantity of antimicrobials used globally in agriculture and food production is difficult to estimate, the evidence suggests that it is at least as great as the amount used by humans. In fact, in some countries, such as the United States, usage in animals actually outstrips human consumption.
Without better policies, the trend line of relative use of antibiotics in agriculture is expected to sharpen as the global middle class expands through economic growth, leading to increased food production, especially as demand for animal protein catches up.
Just as there is a clear correlation between rising levels of human use of antibiotics and growing resistance, the same is essentially true in agriculture. Higher use of antibiotics drives increased drug resistance as bacteria are exposed more often to the antibiotics used to treat them. This is also true for other medicines, such as antifungals.
We will not, nor should we, completely stop the use of antibiotics in animals when treating infections. However, excessive and inappropriate use of antibiotics in agriculture must be reduced. Specifically, as part of the AMR action plan, we need three broad interventions to address the agricultural component of AMR.
First, we need to set a global target to reduce antibiotics in food production to an agreed level for livestock and fish, along with restrictions on the use of antibiotics important for human health. In addition, each country must set an agreed limit based on its agricultural output and resources.
Second, we should develop standards to reduce antimicrobial manufacturing waste released into the environment. This needs to be viewed as a straightforward issue of industrial pollution, with responsibility for containment by all players in the supply chain to reduce resistance from strains emerging through the environment.
Third, we must improve surveillance to monitor usage and progress against targets for improvement. Data have the power to ensure consistent and measurable headway toward goals and to strengthen accountability.
Educate and inform to change behaviors
In the early 1980s, scientific research identified an emerging global public health crisis that was little understood at the time. The world gradually began to understand HIV/AIDS—which it first thought to be a rare form of pneumonia—learning to separate myths from facts and strengthen protection and treatments. Awareness and knowledge of HIV/AIDS grew slowly over time as a global public education effort began to help thwart infection. Few Brits of my generation can forget the U.K. government’s chilling “don’t die of ignorance” campaigns in the late 1980s, warning us of the dangers of HIV/AIDS. For today’s millennial generation, the red ribbon is globally synonymous with one of the most successful and powerful health advocacy movements that we have ever seen.
Now we need to apply the same focus and intensity to AMR. We need to build public awareness of the scale and severity of the problem, strengthen understanding of what individuals should do differently, and then engage in more aggressive public advocacy to focus policymaker attention and drive action.
Simple steps such as encouraging more hand-washing and taking the necessary dosage of antibiotics when prescribed can help, and people must begin to learn about the risks and benefits of antibiotics. Additionally, global education and advocacy can help us make strides to improve water and sanitation infrastructure, particularly in urban areas, to help prevent the spread of infections in communities. Surveillance is another critical pillar of education, as seen in the recent Ebola crisis. If we cannot measure the development and spread of drug resistance—and explain it clearly to the public—we cannot manage it.
We must also be able to retain the expertise and experience of those studying AMR and working in the field if we hope to educate people and policymakers around the world. Specialists must be properly rewarded and supported for their work on AMR, and we must leverage their knowledge to bring data and lessons forward for everyone.
Governments, civil society, academia, and the private sector all have roles to play in educating people on the risks, encouraging effective stewardship at the individual and collective level, and creating specific plans and tools to address the crisis.
Even with the clear AMR threat and an action plan at the ready, it can be hard to feel a sense of urgency to tackle this crisis. On a personal level, I know this well, as I was wholly unaware of the size and severity of this challenge before taking on my role, and that is despite years of experience in global finance that involved discussions about key policy issues with leaders around the world. But we must overcome this complacency and this lack of awareness if we are to use the time we have now—which is limited—to make a difference by addressing AMR before it is an even broader public health crisis with increased loss of life. We must make a choice to become personally enlightened on the issues and take that knowledge forward for additional public education efforts and for advocacy that provides policymakers with further momentum and support. And policymakers must feel the imperative to act now, to take bold steps to force dialogue, set targets, and address systemic risk. AMR knows no borders, and so we also must transcend individual interests and motivations to act together now.