What It Is
A process in which increased use of some prescription drugs causes microorganisms to undergo genetic changes that make them unresponsive to these medications, leaving some diseases more difficult to treat and leading to a global health crisis.
Microbes, or microorganisms, are small living organisms. The main classes of microbes are bacteria, fungi, protozoa, and viruses. One well-known type of microbe is bacteria, a class of single-celled organisms. There are several types of bacteria, including decomposers which break down substances in soil, mutualists which provide essential nutrients to plants, and chemoautotrophs which help to degrade some pollutants.
Most microbes, including bacteria, do not pose a threat to humans. In fact, many bacteria perform helpful functions such as digesting food or detecting harmful substances. However, some microbes can cause human disease by damaging human cells. Common microbes that can cause human disease include:
- Bacteria such as Streptococcus (strep throat), Staphylococcus (staph infections like Methicillin-resistant Staphylococcus aureus (MRSA)), and E. coli (food poisoning);
- Fungi such as dermatophytes (ringworm);
- Protozoa such as Plasmodium (malaria); and
- Viruses such as rhinoviruses (common cold), Influenza (flu), and Ebola.
Researchers have developed drugs called antimicrobial agents to treat diseases caused by microbial infections. Antimicrobial drugs work by either preventing microbes from growing and reproducing or killing them entirely, rendering the microbes unable to continue causing disease.
When antimicrobial drugs are taken over an extended period as prescribed, most of the disease-causing microbes die early in the infection. Disease symptoms can decline at this stage as the medication takes effect and microbes begin to die. However, the microbes that survive at this early stage can continue to cause infection if they are not continually exposed to an antimicrobial drug. Thus, antimicrobial prescriptions often recommend taking the full treatment regimen, even after the symptoms have subsided.
Different types of antimicrobial drugs are required to treat different types of infections. For example, antibiotic drugs, which are designed to fight infections caused by bacteria, are ineffective against infections caused by viruses. A different class of drugs, antiviral drugs, can treat viral infections but cannot treat other types of diseases caused by non-viral microorganisms.
Over time, increased use of antimicrobial agents has led microbes to evolve such that they become resistant to these drugs and maintain the ability to cause disease. This phenomenon, known as antimicrobial resistance, makes disease treatment more difficult because existing drugs are ineffective in counteracting drug-resistant microbes. The infections caused by these microbes must then be treated with increasingly higher doses or with different medications.
Antimicrobial resistance occurs when microbes either change their own genetic code (through a process called genetic mutation) or receive new genetic information from other microbes (through a process called gene transfer). These genetic changes arise when antimicrobial drugs do not sufficiently prevent microbial infection, either because the drug is present in insufficient quantities or because the bacteria have evolved resistance over a sustained exposure. Bacteria that do not evolve such resistance eventually die, while those that do evolve resistance can reproduce and continue to spread infection in the host organism.
People do not become resistant to antimicrobial medication. Instead, the microbes within the body can develop resistance. The presence of drug-resistant microbes in the body makes the person more susceptible to microbe-caused infections and makes these infections more difficult to treat. The link between antimicrobial use and antimicrobial resistance is well established on both the individual and population levels, suggesting that a reduction in inappropriate antimicrobial drug use could mitigate antimicrobial resistance.
Antimicrobial resistance further intensifies when antimicrobial agents are overused or misused. Common ways that these drugs can be misused include:
- Misdiagnosis of an infection, leading to the prescription of an ineffective medication;
- Failure to follow standard protocols such as finishing a complete prescription of an antimicrobial medication;
- Abuse of drugs, such as taking antimicrobial drugs without a prescription; and
- Overuse of antimicrobial drugs to prevent disease in the agricultural system, including the plants and animals that humans eat.
Such misuse of antimicrobial drugs can lead to multi-drug resistant diseases, commonly called “superbugs,” which are resistant to more than one type of antimicrobial medication and are therefore more difficult to treat than other drug-resistant diseases.
Scientists generally recommend taking the full prescription of antimicrobial medication, even after symptoms have subsided. However, some scientists claim that antimicrobial resistance is unlikely to occur if patients stop taking the medication before they run out, and that such a prescription strategy might even increase the risk of antimicrobial resistance because the microbes are exposed to the drug over a longer period. Further research is needed to clarify the best prescription strategy to promote health outcomes while also reducing the risk of antimicrobial resistance.
In addition to the proper duration of antimicrobial prescription treatments, another scientific debate is the feasibility of developing new antimicrobial drugs to replace those to which bacteria have developed resistance. Scientists state that it is possible to develop new antimicrobial drugs, but the feasibility of developing them within a sufficient timeline to avoid global health impacts has been questioned.
If allowed to continue, the antimicrobial resistance crisis could have global impacts on human health. According to a 2014 report by the Review on Antimicrobial Resistance, 700,000 people die from drug-resistant infections every day. A 2019 United Nations (UN) report (SciPol brief available) estimates that annual deaths could rise to 10 million by 2050 unless international governments, organizations, and civil advocacy groups take collaborative action.
Several factors may worsen the effects of antimicrobial resistance in communities that lack access to particular public health necessities. For example, lack of knowledge about the proper prescription and use of antimicrobial drugs can lead to improper use, which may increase the risk of antimicrobial resistance. In addition, infected water, poor waste management systems, and lack of access to general advances in medical care can increase the spread of diseases and exacerbate antimicrobial resistance. These health disparities have led to an up to 80 to 90 percent of infections in some low- to middle-income countries developing drug resistance. Entities such as the UN have proposed global action plans that aim to reduce such health disparities and mitigate antimicrobial resistance.
In addition to its effects on human health, antimicrobial resistance also poses risks to the global economy. According to a 2018 report (SciPol summary available) by the World Health Organization (WHO), patients suffering from drug-resistant infections accumulate higher healthcare costs than patients with conditions that are responsive to medication. This increased cost is due to the increased duration of the illness, as well as the cost of medical tests and the drugs themselves. The burden of these costs is the greatest for low- and middle-income countries, which may not have sufficient resources to keep up with the increased costs and demand for human support. The World Bank estimates that rising costs of food production and healthcare due to antimicrobial resistance could push 28 million additional people into extreme poverty by 2030.
The economic risks associated with antimicrobial resistance are complicated by the fact that changing antimicrobial usage could have its own adverse economic effects. For example, animal products cost less when antimicrobial drugs are used in agricultural practices because these drugs enhance animal growth and feed efficiency. Consequently, modifying current antimicrobial practices could raise the price of animal products and harm animal product producers due to the costs associated with alternatives. Balancing the benefits of reduced healthcare costs with the risks of increased agricultural costs will be essential when considering the potential economic effects of changing current antimicrobial treatment strategies.
Finally, antimicrobial resistance could also lead to environmental impacts due to increased antimicrobial content in agricultural and healthcare waste. Antimicrobial drugs that animals ingest can be excreted as waste in large quantities. Although this waste is often treated with a composting process before being released to the environment, this process may not fully degrade antimicrobial content, leaving some antimicrobial content to be released with the potential to spread through runoff. This antimicrobial waste can negatively influence both wildlife and human communities, especially when the antimicrobial content intensifies drug resistance.
The following statements from antimicrobial resistance experts highlight the need for continued work to respond to this global crisis:
- Thomas Cueni (Director General of the International Federal of Pharmaceutical Manufacturers & Associations, Chair of the Antimicrobial Resistance Industry Alliance), article, The New York Times, April 29, 2019: “Everyone agrees that there is an absolute need for new antibiotics but there is no sustainable market.… I applaud the U.N. for at least putting incentives on the map, but there needs to be more than talk. What’s needed is money.”
- Haileyesus Getahun (Director of the IACG), article, The New York Times, April 29, 2019: “This is a silent tsunami. We are not seeing the political momentum we’ve seen in other public health emergencies, but if we don’t act now, antimicrobial resistance will have a disastrous impact within a generation.”
- Melinda Pettigrew (Professor of Epidemiology at the Yale School of Public Health), article, CNN, April 29, 2019: “If we are going to develop successful strategies to reduce the impact and spread of antimicrobial resistance the scientists, clinicians, veterinarians, policymakers, and members of the community will have to work together to address the problem from a One Health perspective.… Work to reduce the use of antibiotics in livestock and fish farming – especially for growth promotion. And make sure family and community members and children have their vaccines!”
- Lance Price (Director of the Antibiotic Resistance Action Center at George Washington University), article, The New York Times, April 29, 2019: “Even if you don’t care about the suffering of people who drink unclean water and get resistant infections, you still have to recognize that these bacteria don’t recognize international borders. They will come here, and they will kill us. We have to let people know that the problem is closer than they think.”
- Ada Yonath, (Director of the Helen and Milton A. Kimmelman Center for Biomolecular Structure and Assembly, recipient of the 2009 Nobel Prize in Chemistry), Nobel Prize Dialogue, May 22, 2019: “I think a 10-15 fold increase in deaths due to infectious diseases is realistic if we do not find new antibiotics.… Antibiotic resistance is growing at a speed we didn’t expect.”
Several actions from global organizations have aimed to assess the international state of antimicrobial resistance and develop plans to address the crisis. In 2016, the UN organized a High-Level Meeting of the UN General Assembly on Antimicrobial Resistance to improve global health by specifically addressing antimicrobial resistance. This meeting led to the creation of the Interagency Coordination Group on Antimicrobial Resistance, which released a report in April 2019. The report recommends international collaboration to combat antimicrobial resistance by supporting scientific research and improving global healthcare.
At the United States federal level, the Preventing Antibiotic Resistance Act of 2017 (S 629, 115th Congress) (SciPol summary available) sought to reduce antimicrobial resistance by ensuring that approved drugs are safe and effective. However, this bill was not passed through Congress. In 2018, the Strategies to Address Antibiotic Resistance Act (S 2469, 115th Congress) (SciPol brief available) introduced new efforts to reduce antimicrobial resistance by refining government responsibilities for monitoring and reporting on public health. This bill was also not passed through Congress. However, the Pandemic and All-Hazards Preparedness and Advancing Innovation Act of 2019 (Public Law 116-22) (SciPol brief available) was signed into law in June 2019. This policy addresses public health safety concerns including antimicrobial resistance, with a focus on developing new medical treatments and vaccines, funding research efforts, and reestablishing advisory groups to both assess public health risks associated with antimicrobial resistance and advise on government actions.
While these previous efforts have strongly advocated for health outcomes, previous policies have not fully addressed the government regulation and scientific research that would be required to develop alternatives to current antimicrobial medications. Future policy work could focus on these issues in order to address the antimicrobial resistance crisis more completely.
Given the debate on the best ways to prescribe antimicrobial medications, further research is needed to determine what duration of treatment best maximizes health outcomes while reducing the risk of antimicrobial resistance. Some scientists offer a proposed solution in which physicians can prescribe a high dose at the beginning of the infection and lower doses as the symptoms subside. More research can clarify whether this strategy will be effective.
An additional area for future research is the development of new antimicrobial drugs to treat infections. According to experts, it is possible to develop new antimicrobial medications to which current microbes would not be resistant. However, it is not clear whether such drugs could be developed in time to mitigate the potential risks of the global antimicrobial resistance crisis.
Besides developing new medications, future research can also focus on developing vaccines that would prevent infections caused by microbes before they begin. While microbes can develop resistance to medications that are external to the body’s immune system, microbes do not develop resistance to vaccines because vaccines, rather than killing microbes directly, strengthen the immune system to fight infection more effectively. Therefore, newly developed vaccines could reduce or even eradicate some microbe-induced infections. Developing such vaccines is difficult because of financial challenges, hurdles in the therapeutic approval process, and lack of knowledge about how to target the immune system for the best health benefits. Ongoing research contributes to efforts to expand vaccine efficacy against microbial infections and other diseases.
Finally, development of new antimicrobial drugs or other practices to promote animal health in agriculture could further mitigate the effects of antimicrobial resistance. Treating animals with antimicrobial drugs could cause resistance that could worsen infections in humans, but it is unclear whether an alternative animal treatment is achievable and would have a smaller impact on human health.
Further research on antimicrobial resistance may lead to government action worldwide. Developing replacements to existing antimicrobial medications will require new research efforts and funding, which could come from government agencies. In addition, sales of existing antimicrobial drugs will need to be regulated to reduce their overuse and misuse. To take these actions on the global scale, individual government intervention as well as collaboration across countries and sectors will be essential.
Explainer EditorsJennifer Tribble, PhD
Duke SciPol, “Antimicrobial Resistance” available at https://scipol.org/learn/science-library/antimicrobial-resistance (7/2/2019).