Apr 09, 2025 Antimicrobial Resistance: A Serious Global Health Threat Pt 1
In the early twentieth century, medical researchers and entrepreneurs began searching for substances that could kill pathogenic microorganisms—such as bacteria, fungi, parasites, and viruses—while leaving the infected host unharmed. Paul Ehrlich, a German scientist, coined the term “magic bullet” to describe these substances. He demonstrated the potential of this concept when he discovered a compound called Salvarsan, which effectively targeted invading microorganisms in the body without harming the host. Salvarsan, an arsenical compound, proved to be an effective and relatively(!) safe treatment for syphilis and other diseases caused by protozoa, which are single-celled organisms.
The German scientist Gerhard Domagk discovered Prontosil, the following “magic bullet,” in 1932. He had tested various textile dyes manufactured by a nearby chemical company on infected animals. One of these dyes was found to cure mice infected with pathogenic streptococci. Further research revealed that Prontosil was a prodrug; it was metabolized in the body to produce sulfanilamide, the true antibacterial agent. Sulfanilamide drugs became essential medical tools during the Second World War, as crystalline sulfanilamides were sprinkled on open wounds to prevent subsequent infections.
The ultimate “magic bullet” was discovered in 1928 by Alexander Fleming, a microbiologist in London. However, Fleming did not pursue his discovery of penicillin’s antibacterial properties at that time. Eleven years later, in 1939, Howard Florey, an Australian pathologist, and Ernst Chain, a British biochemist, purified and produced enough penicillin to test its effectiveness as an antibiotic. During World War II, penicillin played a crucial, life-saving role. This discovery marked a turning point in medical history, revolutionizing the treatment of bacterial infections. Additionally, the discovery of penicillin stimulated the development of the modern pharmaceutical industry and led to the discovery of many other antimicrobials.
However, there were early signs that antimicrobial use could lead microorganisms to develop resistance to these drugs. In 1924, Silberstein published a report in the Archiv fur Dermatologies und Syphilis on developing protozoal resistance to Salvarsan. In 2018, Dov Stekel wrote to Nature to call attention to this early report of a process that is now threatening the ability of modern medicine to treat many infections by microorganisms.
According to the World Health Organization (WHO), bacterial resistance to antimicrobials was directly responsible for 1.27 million deaths in 2019 and contributed to an additional 4.95 million. The WHO has stated that antimicrobial resistance “puts many of the gains of modern medicine at risk.” For instance, before the development of effective treatments for infections caused by micro-organisms, if a child showed signs of “blood poisoning” in a limb, the recommended course of action was the amputation of the infected limb.
Antimicrobial resistance occurs when humans misuse antimicrobials, leading to the development of resistance genes. Microorganisms can quickly develop resistance, especially if a patient takes too low a dose of an anti-microbial, does not complete the entire prescribed course, or misuses antibiotics for viral infections like colds (since antibiotics do not work on viruses). Additionally, in many regions of the Global South, antibiotics can be obtained without a prescription.
Furthermore, microorganisms that develop resistance genes can transfer them to other microorganisms through a process known as horizontal gene transfer (HGT). To combat this issue, it is crucial to prescribe antimicrobials only when necessary, ensure that patients complete their prescriptions, and advise them not to stop taking the medication even if they start to feel better.
Bacteria have quickly developed resistance to each new antibiotic discovered. Resistance to penicillin, which was first used in the 1940s, became a worldwide problem by the 1950s. Tetracycline was introduced in 1948, but bacteria began to show resistance by the end of the 1950s. Erythromycin became available in 1952, and resistance was observed as early as 1955. In 1960, methicillin, a lab-developed relative of penicillin, was created to combat penicillin resistance. However, methicillin-resistant staphylococcus aureus (MRSA) emerged within a year, leading to its global spread by the late 1960s. Today, drug-resistant infections are the third leading cause of death in the United States, resulting in an estimated 162,000 fatalities each year.
The manufacture and prescription of antibiotics are contributing to the widespread development of antimicrobial resistance around the globe. Professor Sally Davies, England’s Chief Medical Officer, has labeled antimicrobial resistance as “a ticking time bomb,” emphasizing that it is a primary concern for the UK and the entire world—arguably as significant as climate change. Most of the prescribed antibiotics are excreted unchanged, which results in these substances contaminating wastewater streams globally. When sewage treatment is inadequate or non-existent, antibiotics and resistant pathogens can enter rivers, lakes, groundwater, and oceans.
In developed countries within the OECD, 17% of bacterial infections are resistant to some antibiotics. In contrast, Indonesia, Brazil, and the Russian Federation report antibiotic resistance rates ranging from 40% to 60%. Approximately 80-90% of active pharmaceutical ingredients are manufactured in China, while India is the largest producer of finished medicines, particularly private-label generic drugs. Hyderabad, a city in India, is one of the world’s largest centers for drug production, and its environment is heavily polluted with antibiotics. In one lake near Hyderabad, the antibiotic concentration was higher than typically seen in the blood of patients undergoing treatment.
The large amounts of antibiotics entering environments around the world pose a significant problem not only for pathogenic bacteria but also for beneficial bacterial species essential for ecosystems’ healthy functioning. These beneficial bacteria are also negatively impacted by medical antibiotics. The global pool of resistance genes that bacteria can accumulate is known as the antibiotic resistome. This resistome allows resistance genes to spread rapidly across the globe. For instance, the gene responsible for resistance to the antibiotic carbapenem was first identified in India in 2008. By 2012, this resistance gene had been detected over a thousand times in 55 countries.
The use of antibiotics could be reduced in certain situations. The 2016 O’Neill Review on Antimicrobial Resistance (AMR) highlights the issue of diarrheal diseases in low- and middle-income countries, which account for approximately 1.1 million deaths annually. Diarrhea is the second leading cause of death in children. Yet, it is estimated that 60% of the burden of diarrhea could be prevented by providing access to safe water and sanitation. Moreover, two-thirds of diarrheal cases are caused by viral infections that cannot be treated with antibiotics, even though they are often prescribed for this condition. The O’Neill report estimated that universal access to clean water and improved sanitation could eliminate nearly 300 million unnecessary courses of antibiotics each year.
Part II will explore the 70-year debate over antibiotic consumption by farmed animals and its putative role in the global development of antimicrobial resistance.