Strict border control has been instituted; people must self-isolate for a period before entering the city. The sick are quarantined and their contacts are traced and isolated to prevent them from infecting healthy people. Everyone is encouraged to rigorously adhere to personal hygiene measures in slowing the spread of disease. The year is 1347 and the Black Death has struck Europe.

         The bubonic plague, the disease responsible for the Black Death, caused many of the worst epidemics in history. It is estimated that between 30% and 60% of Europe’s population was felled during Europe’s first battle with the plague, which lasted from 1347 to 1352. The plague ravaged Europe in a series of waves between the 14th and 18th century, killing millions. Outbreaks of the plague continue into modern times. In the mid 19th century there was an outbreak of plague in China which later spread to Australia in the early 20th century. While the plague has, for the most part, been defeated, there are still approximately 2000 cases each year.

         It may come as a surprise that the bubonic plague was caused by a bacterium, called Yersinia Pestis, not a virus. While there are modern bacterial epidemics, like Tuberculosis, most epidemics in the last 100 years including Covid-19, SARS, HIV/AIDs, Polio, Ebola and the Spanish Flu have been viral rather than bacterial. For the most part, the developed world has been spared from devastation at the hands of bacteria, thanks to improved hygiene practices together with one of the most important discoveries of the 20th century: antibiotics.

         The first antibiotic, Penicillin, was discovered accidentally by Sir Alexander Fleming in 1928. Sir Fleming discovered Penicillin while researching a bacterium called Staphylococcus. After coming back from vacation, he noticed one of the petri dishes he was using to grow Staphylococcus had grown mold. He found that the Staphylococcus was growing all over the dish except for the area surrounding the mold. Sir Fleming concluded that some property of the mold was inhibiting the growth of Staphylococcus. Sir Fleming found that the mold, Penicillium notatum, was not only able to inhibit the growth of Staphylococcus, but it could also kill a wide variety of bacteria.

         With that discovery, the era of antibiotics commenced. Antibiotics not only prevent mass death in epidemics like the bubonic plague, but are also used to treat a variety of everyday ailments that were once considered deadly, like pneumonia. It is estimated that antibiotics alone have extended the average life expectancy by 20 years.  

         However, the effectiveness of antibiotics is under threat. Bacteria have begun to develop immunity against antibiotics. In part, this is a natural process. Over time, bacteria acquire random mutations, some of which grant them greater resistance to antibiotics. If a colony composed of both antibiotic resistant and non-antibiotic resistant bacteria is exposed to antibiotics, only the bacteria that is less vulnerable to antibiotics will survive, resulting in a colony of bacteria which is more resistant to antibiotics. This process repeats itself many times leading to the growth of bacteria colonies that are immune to antibiotics.

         While antibiotic resistance is a natural process, it has been hastened by the reckless use of antibiotics in both the medical and agricultural industries. In medicine, antibiotics are often prescribed even where there is no proven medical benefit. For example, it has been estimated that antibiotics are prescribed for approximately 38% of the respiratory tract infections, which include coughs, colds and sore throats, that are referred to physicians. It is estimated that approximately 46% of these prescriptions are unnecessary because the disease is not sufficiently severe or the infection is viral rather than bacterial.

         Antibiotics have also been overused in the agricultural industry. These drugs are used by farmers to treat bacterial infections in livestock and crops. Small doses are often given to healthy animals to encourage growth, consume less food and improve disease-resistance. The constant exposure to antibiotics quickly leads to the development of antibiotic-resistant bacteria. This harmful practice is especially prevalent in developing countries where there are fewer regulations against the overuse of antibiotics.

         Antibiotic resistance has already become a large issue. The CDC estimates that 2.8 million Americans are infected with antibiotic-resistant bacteria and 35,000 Americans die from antibiotic-resistant bacterial infections each year. In developing countries, like India, cases of antibiotic resistance are even more common. Right now, many of these bacterial infections can still be treated with “last resort” antibiotics, which are more expensive antibiotics that are used less frequently. However, bacteria develop immunity even to these “last resort” antibiotics.

         Antibiotic resistance has become an increasingly large problem over the last 50 years, as there have not been any new antibiotic mechanisms discovered since the 1970s. Antibiotics are not being developed because many of the obvious ways to kill bacteria have been used in previous generations of antibiotics, making it difficult and expensive to develop new antibiotics. Researchers estimate that developing a new antibiotic would cost approximately $1.5 billion U.S, but would only bring in approximately $46 million U.S of revenue a year. Because of such financial barriers, very few large pharmaceutical companies are trying to develop new antibiotics.

         Even though big pharmaceutical companies have largely given up on developing new antibiotics, there have been some exciting new advances in the field coming from smaller companies and researchers in academic institutions. One promising area of research lies in the use of bacteriophage therapy, either in conjunction with antibiotics or as a stand-alone therapy. Bacteriophage therapy uses a class of viruses that target bacteria, called bacteriophages, to kill bacteria that are harmful to humans. While bacteriophage therapy has not been approved for use on humans in the EU or the U.S, there have been many clinical trials that demonstrate its utility in certain biological infections. One limitation to bacteriophage therapy is that bacteriophages are very specific, as each individual bacteriophage targets one strain of bacteria. Contrastingly, antibiotics work on a wide array of different bacteria. This means that multiple types of bacteriophages are needed to treat infections that are composed of multiple strains of bacteria. In particular, bacteriophage therapy may not be a practical treatment for certain ailments, such as burn wounds, which tend to be colonized by multiple strains of bacteria.

         As the world slowly begins to emerge from the Covid-19 pandemic, it is important we begin to focus on antibiotic resistance, the next big threat to global health. It is estimated that antibiotic-resistant bacteria could kill up to ten million people per year by 2050, unless steps are taken to prevent antibiotic resistance. However, there is hope. Through a combination of more responsible use of antibiotics and more antibiotic research, the antibiotic resistance crisis can be averted. The world must come together to invest more money into antibiotics research, train doctors to limit antibiotic use to cases where it is medically necessary and prevent the overuse of antibiotics in agriculture. Luckily, unlike the Covid-19 pandemic, the antibiotic resistance pandemic comes with advance warning. We must act on it, before it is too late.

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