The Rise and Fall of Antibiotics

Many of us cannot remember a time when antibiotics were not around. Omnipresent in clinical settings, antibiotics have been playing crucial and diversified roles in medicine ever since the discovery of penicillin. It is not to anyone’s surprise, therefore, that bacterial resistance to this class of drugs has been described as “almost as big, if not bigger, than climate change,” and even as “the end of modern medicine.” To understand the scope of the issue, we must first tackle the questions of why bacteria develop resistance, how the overuse of antibiotics is changing the evolutionary landscape of microbes, and what is being done about it, both in Canada and around the world.

Understanding Antibiotic Resistance

Antibiotic resistance is a phenomenon that is relatively easy to misunderstand. It occurs when medicines traditionally used to treat bacterial infections are no longer effective as a result of bacteria evolution. It is, in fact, the pathogens, or bacteria, that become resistant to the antibiotics, not the human or animal consuming them. Antibiotic resistance does not discriminate between age or geographic region and occurs in virtually all corners of the globe where antibiotics are prescribed, albeit it affects some regions faster and more severely than others. Many common illnesses treated by antibiotics, such as pneumonia, tuberculosis, gonorrhea, and salmonellosis, are becoming particularly harder to treat as a result of antibiotic resistance.

Not only are antibiotics lifesaving medications in their own right, but they also play key roles in surgery and other customary medical treatments, such as chemotherapy. Preventing or treating infections in patients with chronic diseases such as diabetes, rheumatoid arthritis, or end-stage renal disease, antibiotics also play key roles in preventing the development of infections in organ transplants, cardiac surgery, and joint replacements. As a result of their tremendous impact on human health, antibiotics have been a major factor in increasing the human lifespan, which grew from 56.4 years in the 1920s for the average American to around 80 years today. In other parts of the world, antibiotics are an integral tool to keep the mortality rates caused by food-borne infections in check.

Antibiotics in Action

Antibiotics have been an indispensable treatment option for millions of lives since the discovery of penicillin in 1928 by Sir Alexander Fleming. Dubbed the “miracle drug,” penicillin’s commercial success first took root during World War II, where it cured common battlefield infections such as pneumonia. Penicillin soon became available to the public and morphed into a global phenomenon. However, the history of resistance is almost as old as the drug itself. Shortly after its introduction, penicillin was no longer as potent as it was when it first arrived, as penicillin resistance became a threatening concern. New “beta-lactam” antibiotics were discovered by the 1950s in response to this resistance, but the first case of methicillin-resistant Staphylococcus aureus was spotted soon, both in the United Kingdom and in the United States. In response to methicillin resistance in S. aureus as well as in coagulase-negative staphylococci, yet a new drug called vancomycin was introduced. The cycle began again in 1979 and 1983 when cases of vancomycin resistance were, not surprisingly, reported in coagulase-negative staphylococci. Resistance can be seen as a rule, rather than the exception, as it has been seen in nearly all antibiotics that have ever been developed.

Causes of Antibiotic Resistance

One of the major causes of antibiotic resistance is the overuse and misuse of antibiotics. Sir Alexander Fleming himself predicted that the “public will demand [the drug and] … then will begin an era … of abuses.” But how is it that the more an antibiotic is used, the less effective it becomes? The answer boils down to understanding the mechanisms of evolution. As a result of natural selection, antibiotics remove the competitors that respond to the drug and leave the ones that can tolerate it, giving the resistant ones a “boost” in their ability to survive and reproduce. This enables them to leave relatively more copies of their genes in the gene pool compared to the non tolerant individuals. Over many generations, we can expect the population to contain many of the resistant genes that initially gave the surviving bacteria a leg up. Resistance occurs spontaneously through mutation, but since genes can be transferred horizontally in bacteria – meaning that genes can be acquired anew for each generation, from nonrelatives – resistance can also be transferred among different species of bacteria. If antibiotics are consumed frequently and at high dosages, this only increases the selection pressures against the non-resistant strains and makes the fitness advantages of the resistant ones even more beneficial. Unfortunately, we see exactly this overuse of antibiotics in parts of the world where antibiotic use is largely unregulated and antibiotics are readily available over the counter, without the need for a prescription. According to the IMS Health Midas database, 22.0 standard units of antibiotics – with one unit roughly equivalent to one pill or capsule – were prescribed per person in the United States in 2010.

In Canada and around the World

What does this mean for Canadians? A recent article by the CBC states that antibiotic resistance costs Canada’s national healthcare system around $1.4B per year and is likely to kill close to 400 000 Canadians by the year 2050. Furthermore, the percentage of resistant bacterial infections is projected to grow from 26% in 2018 to 40% by 2050. This results in about $120B in hospital expenses and a $388B cost to the GDP cumulatively over the next three decades. However, the implications of antibiotic resistance are sadly not confined to the economic realm but spill over to the social fabric as well. The impact of resistant infections will most likely be unequally distributed among socioeconomic groups, making resistant infections more frequent in already marginalized groups. As for Canada’s actions towards antibiotic resistance from a global perspective, the country has been falling behind on an effective surveillance system of antimicrobial resistance and the use on the federal, provincial, and territorial levels, according to a recent report named, “When Antibiotics Fail,” commissioned by the Public Health Agency of Canada.

The same report emphasizes the importance of improved stewardship. This not only encompasses the careful use of antibiotics but also the strategies to prevent infection and control its spread through strict hygiene measures. The report also calls for more flexible regulations and incentives to promote the discovery of new antimicrobials as another major cause of antibiotic resistance is the relative paucity of new broad-spectrum antimicrobials that have been discovered recently. Alternatives to antibiotics, including vaccines using phages, are being actively researched to treat resistant infections. At the individual level, it is crucial that one only uses antibiotics when prescribed to do so and to follow more conservative guidelines regarding antibiotic use. For healthcare professionals, it is crucial to inform patients of the correct amount of antibiotic intake and the dangers of misuse. In addition, hygiene should be given high priority in healthcare workplaces to minimize the spread of infection.

At the international level, members of the World Health Organization have agreed that antibiotic resistance is a concern of global significance and have correspondingly signed the Global Action Plan, which details the best practices each country can take to reduce resistance. Antibiotic resistance as a global issue was addressed by the United Nations before the General Assembly in 2016, and a year later, in May 2017, the G20 leaders signed a monumental declaration on global health, which addressed antibiotic resistance. According to the National Health Service of England, antibiotic prescriptions reduced by 5.3% in 2015, in comparison with 2014. Furthermore, the US National Institutes of Health and the Biomedical Advanced Research and Development Authority have set up a fund called CARB-X, which allots $48M to support antibiotic drug discovery projects.

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