The world is fixated on viruses thanks to COVID-19. Public and private sectors have mobilized extraordinary levels of resources in tackling the pandemic, including developing vaccines in record time and antiviral and antiretroviral treatments for the disease. In the process, however, another major microbial threat has been neglected. In a study published in The Lancet in January, researchers at the University of Washington estimated that 1.3 million people die each year from bacterial infections that are resistant to antibiotics. Such infections kill more people annually than do HIV/AIDS, diarrhea, and malaria. Antibiotic resistance causes more deaths than any infectious disease apart from COVID-19 and tuberculosis.

These new estimates have brought the problem of antibiotic resistance out of the shadows and confirmed what most public health experts, researchers, and clinicians have known for a long time: the overuse of antibiotics risks making the drugs useless and brewing the next major health crisis. As incomes around the world have risen, so has the consumption of antibiotics—in particular in the agricultural sector, where the drugs are used at an industrial scale on animals. Such extensive use creates the conditions that allow bacteria to become resistant to the drugs. Antibiotic resistance could well become the leading cause of death by infectious disease in the coming years. In 2016, the United Nations General Assembly called for global action to protect the world’s antibiotics, but there has been little progress since. The consequences of inaction are serious. With antibiotics rendered ineffective, societies would return to a world of greater death and deteriorating life expectancy in which common surgeries, transplants, and chemotherapy become much more dangerous because of the high risk of untreatable infection.

THE ETERNAL WAR OF BACTERIA AND FUNGI

The ability of bacteria to evade treatments predates the modern use of antibiotics. Fungi, from which many antibiotics are derived, and bacteria have been in competition for at least hundreds of millions of years. Some bacteria have, over time, developed mechanisms to resist the attacks of fungi, such as thicker, less permeable cell walls; the ability to neutralize the enzymes produced by fungi that would otherwise kill them; and the ability to pump out the fungal threat.

But that capacity to resist has grown immensely in the era of antibiotics. These drugs lead to their own undoing in the following way: When administered, antibiotics may successfully kill off the majority of bacteria causing an infection. But even as susceptible bacteria die out, bacteria that can fend off the drugs survive. With repeated antibiotic use, the population of bacteria is increasingly made up of the ones resistant to the drugs—in much the same way that the continued application of weed killers on a lawn eventually leads to a lawn filled with hardy, resistant weeds. 

Over the past eight decades, societies have used antibiotics at an industrial scale—totaling hundreds of thousands of tons per year—not just for treating humans with illnesses but also to support the production of meat since antibiotics help fatten poultry, cattle, and pigs. Humans and animals frequently share bacteria, so drug-resistant bacteria amplified in animals can jump to humans. In the pre-antibiotic era, around one in ten million bacteria would be resistant to antibiotics—a holdover of information from the bacteria-fungal wars. With the constant use of antibiotics and Darwinian selection—bacteria that are susceptible to antibiotics are unable to survive, while those that are not susceptible do—ten to as much as 90 percent of bacteria causing infections are now resistant to previously effective antibiotics. Many patients now get infections that are not treatable with any available drug.

LESS IS MORE

Untreatable bacterial infections affect people everywhere, in both rich and poor countries, but most deaths related to drug resistance are in South Asia and sub-Saharan Africa. Unlike COVID-19, which moved rapidly around the world, antibiotic resistance is a slow pandemic and has been spreading at a more gradual pace. The cumulative damage it has caused over the years likely exceeds the current toll of COVID-19. Antibiotic resistance, however, hasn’t received the same urgent attention that COVID-19 has. And while roughly $50 billion is spent each year on tackling HIV/AIDS in low- and middle-income countries, global spending on antimicrobial resistance amounts to less than $1 billion per year. Much of this limited spending is concentrated in high-income countries. 

But several steps can be taken now to head off this looming catastrophe. Agricultural producers of meat and poultry must drastically reduce their usage of antibiotics. Currently, 80 percent of the world’s antibiotics are used industrially to fatten the billions of poultry, pigs, and cattle raised every year. Antibiotic consumption anywhere provides resistant bacteria a better chance of survival. Major poultry producers such as Purdue and Tyson have shown that it is possible to raise large flocks of chickens without putting them on a steady diet of antibiotics. The United States has seen a 40 percent decline in antibiotics used in agriculture since 2014 without any accompanying reduction in animal health. But much more can be done.

If farmers in the United States were to use antibiotics at the rates that European farmers do, total consumption in the United States could go down another 50 percent. Authorities should improve biosafety standards on farms to prevent animals from getting infected in the first place, make investments in new vaccines to prevent diseases, and get farmers to commit to adopting the practices that are already in place in the best-run facilities. Simply put, the meat and poultry industry should try to meet the standards of limited antibiotic use achieved in European countries. Consumers can also drive change by demanding antibiotic-free meat; many have no idea the food they eat has been raised using antibiotics.

As much as 90 percent of bacteria causing infections are now resistant to antibiotics.

People also need to stop taking antibiotics unnecessarily. Researchers have deemed roughly half to 70 percent of the antibiotics used by humans to be inappropriate. In other words, the drugs provide no real benefit to the patient even as they help create microbial resistance. Antibiotics are easily available over the counter without a doctor’s prescription in many countries, but these are also places where it can be hard to access a doctor and an antibiotic could mean the difference between life and death. Doctors in many countries around the world have been inappropriately treating COVID-19 with antibiotics even though there is no clinical evidence to support such use. In India, for instance, authorities removed antibiotics from the list of recommended medicines to treat COVID-19 only in January, nearly two years into the pandemic. Any new antibiotics developed in the future will meet the same fate as the ones already in use unless governments, public health officials, clinicians, and the public in general understand the importance of discouraging inappropriate antibiotic consumption.

Overall consumption can be reduced in two ways. First, preventing infections will help lower the demand for antibiotics. Increased vaccination coverage against both bacterial and viral diseases can help. For instance, the broader embrace of seasonal influenza vaccinations—the flu can lead to bacterial infections—could avert hundreds of millions of antibiotic prescriptions. Vaccines against pneumonia and rotavirus have also been shown to be effective in reducing infections, obviating the eventual need for antibiotics. New vaccines against pathogens such as klebsiella and staphylococcus must be developed. In much the same way as governments have prioritized vaccine development during the COVID-19 pandemic, they need to encourage the rapid investment in vaccines to prevent key bacterial infections. Public health authorities should also improve infection control protocols in hospitals. A small proportion of patients who are admitted to hospitals each year acquire an infection during their hospital stay.  Reducing the occurrence of these infections will reduce the need for antibiotics. 

The second way is to reduce the unnecessary use of antibiotics. The average American consumes more than twice as much antibiotics every year as the average Scandinavian, despite not being any sicker. Authorities should educate physicians to prescribe fewer antibiotics, make it easier for them to prescribe alternatives to antibiotics, including medicines that relieve cough and cold symptoms, and use the correct diagnostic tools to ensure that an infection is indeed caused by bacteria before they choose to prescribe an antibiotic. 

Governments and the private sector also need to replace the antibiotics that no longer work. The PASTEUR Act being considered by the U.S. Congress provides much needed incentives to support antibiotic developers. Several major initiatives, such as the REPAIR Impact Fund, seek to leverage public and private funding to boost new antibiotic development. The Biomedical Advanced Research and Development Authority, a U.S. government agency, is an important funder of research into new antibiotics. The U.S. Centers for Disease Control and Prevention spends nearly $300 million a year on antibiotic resistance. But funding levels are low globally, particularly in low- and middle-income countries—likely less than a few hundred million dollars in total. A serious effort to develop new antibiotics and vaccines will likely require investments of around $10 billion a year to ensure that antibiotics remain useful. Private companies are not willing to make those investments on their own without some public sector support since they do not see antibiotics as a profitable investment. There is simply no alternative to a strong government investment in these valuable drugs that make modern health care possible. 

A WORLD SAFE FOR ANTIBIOTICS

New strains of resistant pathogens already move freely across countries. It is only because testing for antimicrobial resistance is poor that the numbers of cases and deaths caused by drug-resistant infections are not on the front pages of newspapers every day. But the situation is no less serious than the COVID-19 pandemic. Many of these deaths are preventable. 

In addition to the necessary steps detailed above, governments and the private sector need to generate, update, and share information and analysis about resistance to antibiotics, in much the same way that the Intergovernmental Panel on Climate Change tracks the climate crisis.  The issue of antibiotic resistance crosses into many sectors, including medicine, public health, pharmaceutical manufacture, agriculture, aquaculture, water, and sanitation. Progress is unlikely without clear direction at global, national, and local levels that unites all these areas. 

Countries have paid heavily for not preparing adequately for the current pandemic. They should not repeat that mistake for this creeping pandemic that will only grow more intractable if not addressed.

Correction appended (March 1, 2022)

Owing to editorial error, an earlier version of this piece suggested that bacterial cells contain mitochondria, organelles that generate chemical energy. Bacteria do not contain mitochondria. The reference has been removed.

The essay also claimed incorrectly that fungi and bacteria have been in competition for 3.5 billion years. Scientists believe fungi emerged only around one billion years ago. The reference has been amended.

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  • RAMANAN LAXMINARAYAN is Senior Research Scholar at Princeton University and a member of the U.S. Presidential Advisory Council on Combating Antimicrobial Resistance. 
  • SALLY DAVIES is Master of Trinity College at Cambridge University and UK Special Envoy on Antimicrobial Resistance.
  • More By Ramanan Laxminarayan
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