Prior to the development of antibiotics, an infection could more often than not, lead to one’s demise. A sore throat, simple skin infection, or a urinary tract infection could potentially be life threatening. However, with the development of the first antibiotic, new possibilities arose, along with hope and optimism. Previous diseases that would ultimately lead to death could now be cured and sometimes in a matter of days.
Penicillin was initially hailed as a “miracle drug,” as it had rapidly become the cure for many diseases. Penicillin was widely used after it first came to the market and was used to treat infections such as sexually transmitted diseases, skin and soft tissue, pharyngitis, and respiratory infections. Penicillin even found its way into World War II, as the United States pushed for penicillin to be used to save soldiers’ lives by treating a variety of diseases such as blood stream infections or infections secondary to injury or surgical operations.
The United States, through commercial scale fermentation, had produced 4 million sterile packages of penicillin per month during World War II. However, as the use of penicillin soared to meet the demand of those that needed its cure, an interesting and frightening side effect was noted, called antimicrobial resistance. For bacteria to survive exposure to penicillin, it would ultimately “learn” or adapt to overcome and defend itself against this new powerful weapon designed to protect humanity. This natural selection of more resistant bacteria was inevitable and an evolutionary process, as bacteria soon developed mechanisms of becoming resistant. These mechanisms include the development of antibiotic resistance genes harbored by the bacteria. When a bacteria mutated and developed these resistance genes, penicillin would no longer be effective against it, making the bacteria even more dangerous.
Penicillin resistant bacteria was initially noted by the father and creator of this miracle drug himself, Alexander Fleming. Alexander Fleming is credited with penicillin discovery in 1928, although it took him many more years to convince the scientific community of its possibilities of curing people from infections. In 1940, it finally came to the market with the help of other scientists. In 1945, in an interview with the New York Times, Alexander Fleming, a recent Nobel Prize recipient for this amazing discovery, warned the world that the misuse of this new drug, could lead to antimicrobial resistance. Fleming went as far as to say, “The thoughtless person playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penicillin-resistant organism.”
Eighty-two years after the first antibiotic was introduced, we are now seeing antimicrobial resistance in an unprecedented manor. The Centers for Disease Control and Prevention (CDC) notes that 2.8 million antibiotic-resistant infections occur in the U.S. each year with more than 35,000 people dying as a result. Side effects of antibiotics such as Clostridioides difficile lead to an additional 3 million infections with 48,000 deaths. In addition to the CDC, the World Health Organization (WHO), and the United Nations (UN) have now identified antimicrobial resistance as a global and public health concern. The WHO has implemented the Global AMR response in an effort to combat this rising threat. The UN has warned that if no action is taken, drug resistance disease can lead to 10 million deaths by each year by 2050 and force up to 24 million people into extreme poverty by 2030.
Although antimicrobial resistance is a natural phenomenon that occurs when bacteria are exposed to antibiotics, this process is exacerbated and accelerated with the overutilization of antibiotics. The CDC estimates that at least 30% of antibiotic prescriptions are unnecessary. This translates to 47 million excess antibiotic prescriptions each year. In 2015, the White House released the National Action Plan for combating antibiotic resistant bacteria, which set a goal of reducing inappropriate antibiotics. The Joint Commission, an institution that provides regulator standards for hospitals and nursing homes, and the Centers of Medicare and Medicaid Services (CMS) has made it mandatory to implement programs to reduce the overuse of antibiotics, called antimicrobial stewardship programs[9,10]. However, despite the global effort to reduce antibiotic overutilization, and regulatory standards implemented, we are still seeing antimicrobial resistance rise, along with increasing mortality and morbidity. This global health crisis has no boarders, as countries around the world are seeing similar trends.
Antimicrobial resistance can be viewed similarly to climate change in many ways.Both issues are attributed to human activity and its resolution involves global collaboration. As noted by Andrew Jameton and Howard Frumkin, in Chapter 10 of Environmental Health Ethics, in order to effectively solve these large problems, environmental justice needs to be addressed. As it pertains to antimicrobial resistance, low socioeconomic regions with limited resources are often left without the tools needed to combat antimicrobial resistance. In some studies, it was noted that 80% of counties have below average infectious disease specialists or no infectious disease specialists at all. This disproportionately effects rural parts of the United States.
An important argument that can be made, is that the healthcare system has a moral obligation to provide the resources needed to combat antimicrobial resistance. There is a clear gap in the ability to provide effective antimicrobial stewardship throughout the US. Most effective antimicrobials stewardship programs are in academic institutions or large hospital centers with the resources to fund these programs. For outpatient facilities, or those facilities with limited resources, antimicrobial stewardship programs remain on the wayside either by not being implemented at all or implementation of a less than par program to meet minimal requirements.
Newer technologies using artificial intelligence (AI) and machine learning give access to infectious disease expertise in settings that otherwise would not. Data analyzed by AI systems can track, record, and monitor infection and antimicrobial resistance trends while also providing real time evidence-based guidance on the appropriate utilization of antimicrobials. The ethical consideration of this level of automation for disease surveillance was addressed in the article by Michelle M. Mello and C. Jason Wang, Ethics in Governance for Digital Disease Surveillance. Although using advanced technologies to provide the tools needed to solve antimicrobial resistance appears logical, it’s important to assure inequities and bias still does not persist based on limited excess to facilities using these newer technologies. Patients’ privacy can be a potential ethical concern as this may go beyond what patients are accustomed to as it pertains to who is viewing their data.
Clinicians must be cognizant of antimicrobial resistance and that their direct actions can have indirect dire consequences. Currently, there are no regulations or mandates that require antimicrobial stewardship programs in the outpatient setting. This is particularly concerning, as a large portion of inappropriate antibiotic prescribing occurs in the outpatient setting. There is currently no accountability for healthcare providers prescribing antibiotics outside of evidence-based recommendations. In many situations, healthcare providers may not even be aware of new evidence and the latest guidelines on antimicrobial prescribing. Most healthcare providers are not specifically trained in the specialty of infectious disease. In addition, infectious disease specialists are paid considerably less than other medical specialties, which may account for the many medical school graduates gravitating away from this specialty. It is clear that the growth of infectious disease specialists is not meeting demand.
Global health issues are often difficult to solve as it involves collaboration on multiple levels, including the individual level, local and federal government, and collaboration between nations. We see this level of complexity when trying to find solutions to climate change, and similar obstacles exist with regard to antimicrobial resistance. An emphasis on ethical and moral responsibilities of healthcare providers, insurance companies and the government, in providing solutions is essential. Left without accountability, we are bound to see these problems worsen. In addition, counties must unite and work together to solve these global issues. What will affect one country, is bound to effect another, as COVID-19 has clearly demonstrated. Newer technologies can help bridge the gap and provide important tools to underserved areas, that otherwise would have no access innovative solutions. An open mind should be kept so that new innovations can be implemented to help solve these issues, while maintaining the ethical and moral standards expected.
- Chain E, Florey HW, Gardner NG, Heatley NG, Jennings MA, Orr-Ewing J, et al. Penicillin as a chemotherapeutic agent. Lancet. 1940;236:226–8. 10.1016/S0140-6736(01)08728-1
- Quinn R. Rethinking antibiotic research and development: World War II and the penicillin collaborative. Am J Public Health. 2013;103(3):426-434. doi:10.2105/AJPH.2012.300693
- Tan SY, Tatsumura Y. Alexander Fleming (1881-1955): Discoverer of penicillin. Singapore Med J. 2015;56(7):366-367. doi:10.11622/smedj.2015105
- Sillankorva S, Pereira MO, Henriques M. Editorial: Antibiotic Alternatives and Combinational Therapies for Bacterial Infections. Front Microbiol. 2019;9:3359. Published 2019 Jan 18. doi:10.3389/fmicb.2018.03359
- Jameton, A., Frumkin, H. “Environmental Health Ethics.” in Frumkin, Howard, ed. Environmental Health: From Global to Local, 3rd ed. Jossey-Bass, 2016.
- Where Is the ID in COVID-19: Rochelle P. Walensky, MD, MPH, Daniel P. McQuillen, MD, Sara Shahbazi, PhD, John D. Goodson, MD.https://doi.org/10.7326/M20-2684
- Frenkel A, Gross D, Levi S. (2020) Artificial intelligence: A solution to the need for outpatient antimicrobial stewardship. InfectionControl.tips. 6:1-9.
About the Author
Ari Frenkel is a board certified infectious disease and internal medicine physician as well as a children’s book author and musician. He has served as infectious disease medical director in multiple settings and established successful antimicrobial stewardship programs in underserved areas. His experience includes medical director of infectious disease for RCCH (Regional Care Partners), a corporate hospital system that had 14,000 employees and 2,000 doctors across 16 hospitals throughout the United States. Dr. Frenkel also served as a medical director in the nursing home and rehab setting and is well versed on infectious diseases pertaining to long term care. He served as a clinical instructor and preceptor for Lincoln Memorial University-DeBusk College of Osteopathic Medicine and Alabama College of Osteopathic Medicine. Currently, Dr. Frenkel is expanding his education and obtaining his masters in public health, via Yale’s School of Public Health. Due to the rising global threat of antimicrobial resistance, Dr. Frenkel dedicated his career to solving this predicament. He co-founded Arkstone Medical Solutions, a biomedical technology company that uses artificial intelligence and machine learning to democratize infectious disease expertise across many clinical settings. Using this technology, thousands of physicians and healthcare facilities now have access to the tools they need to provide antimicrobial stewardship and better care to their patients.