Indian estate agent Ajit Varma died of a hospital-acquired multidrug-resistant infection. When he first checked into an overcrowded hospital in South Delhi, Varma had only a simple case of bronchial asthma, but his condition quickly deteriorated. Asthma gave way to pneumonia, extreme pain in his extremities and a disconcerting amount swelling. The short-staffed hospital however, treated the particularities of his health with little interest. Indeed, two weeks later, when Varma lost his vision on the eve of his death, his doctor dismissed the symptom and told the discombobulated man: “one needs to open one’s eyes to see things”. Although it would be natural to conclude that Varma was killed by the gross negligence and apathy that plague Indian private hospitals, the truth is even more troubling. After being transferred out of the ICU, Varma contracted multiple infections including methicillin-resistant Staphylococcus aureus that did not respond to multiple antibiotics. Varma is survived by his family, including myself, and the families of the other 700,000 people who lose their lives to antimicrobial resistance or AMR every year.

 

What is antibiotic resistance?

It is hard to overstate how elegantly Darwin’s theory of evolution applies to antibiotic resistance. As a category of drugs that fight infections caused by bacteria, most antibiotics work either by preventing the creation of new proteins or by impeding the synthesis of cell walls. However, when antibiotics fail to eliminate all the pathogens in an organism, certain strains mutate. Natural selection then dictates that these mutated strains can replicate with more ease because the lower dose of antibiotic kills all the susceptible, non-mutated bacteria. The result is the development of “superbugs,” like the one Varma contracted, which are hard to treat with our existing classes of antibiotics.

Although antibiotic misuse is a natural phenomenon, human misuse is accelerating the problem. In his Nobel Lecture in December 1945, Alexander Fleming issued a prescient warning about the possible future inefficacy of antibiotics. Fleming used the “hypothetical illustration” of a Mr. and Mrs. X to emphasize a simple, yet critical guideline for taking antibiotics: “If you use penicillin, use enough”. In Fleming’s parable, Mr. X consumes only a palliative amount of penicillin to treat his streptococci, and therefore passes on a newly resistant strain of pneumonia to his wife. Tragically Fleming’s advice has gone unheeded and misinterpreted all over the world due to a prevailing culture of treatment. In developing countries, nearly 75% of people erroneously believe that individuals rather than bacteria develop resistance to antibiotics. Accordingly, people are more inclined to start and stop taking antibiotics without reservation. When, in countries like India, antibiotics are easily available over the counter without a prescription, people often treat themselves without first confirming whether they are actually suffering from a bacterial infection as opposed to a viral one. Because viruses lack cell walls, antibiotics are unable to kill them, and improper diagnosis leads to unnecessary consumption of drugs. Similarly, in Western countries, doctors often feel comfortable prescribing antibiotics before they know whether the infection is viral or bacterial. Since, if the underlying condition is viral it will eventually resolve itself, these doctors often think it matters little if treatment is ineffectual.

 

On the Farm

On top of the irresponsible human consumption, there is also overuse of antibiotics on farms. Antibiotics were first discovered to increase the growth rate of livestock and improve feed efficiency by making animals gain more weight in 1950. Today 80% of all antibiotics administered in the United States are given to livestock. Since these antibiotics are overused, misused, and necessary to treat infections in people, burgeoning antibiotic resistance on the farm has severe consequences for human beings. Of particular concern are recent developments involving colistin, a drug used to treat gram-negative infections that is reserved as a last resort and rarely used in humans because of the damage it can cause to the renal and nervous systems. However, much to the alarm of the scientific community, the discovery of a colistin resistant mcr-1 gene last November rendered certain types of superbugs resistant to even this antibiotic. Scientists believe that the overuse of colistin in Chinese farms and livestock probably led to a mutation in the bacteria. This mutated gene was then transferred from a microbe that infects livestock to a microbe that infects human beings through a process called horizontal gene transfer that allows resistance to jump from species to species. Resistance to colistin has severely depleted our defense arsenal against bacteria that can cause pneumonia, urinary tract infections, and sepsis, and has also increased the fatality risk associated with routine procedures such as hip replacements.

 

The Cautious Optimism of Jim O’Neill

The same mechanism that allows bacteria to develop resistance may also present a way for us to bring the situation under control. When a bacterium mutates and becomes more resistant it uses up a tremendous amount of its stored energy. Therefore bacteria only becomes resistant to an antibiotic when repeatedly exposed to the drug, and it is logical to assume that resistance would decline if antibiotics were used more sparingly. Indeed through a rigorous combination of scientific innovation, global co-operation, and economic pressure, the opportunity remains to retrieve antimicrobials from the brink of obsolescence. An influential report sponsored by the British Government and assembled by Lord Jim O’Neill–popular for coining the term BRIC (Brazil, Russia, India, China) economies–suggests that the scourge of antimicrobial resistance can be effectively tackled. By launching targeted public awareness campaigns about the proper use of antibiotics, reducing the intake of antibiotics by livestock and humans, and simultaneously increasing the number of antibiotics available on the shelves, the O’Neill report concludes that combating antimicrobial resistance is not just possible, but also affordable. While the economic cost of antimicrobial resistance is predicted to be $100 trillion a year by 2050, the cost of action against rising resistance is estimated to be a much more modest $40 billion dollars a decade. Furthermore, the report provides accompanying recommendations to reduce resistance that include prohibiting the use of antibiotics that are vital to humans in livestock, carefully surveying the administration of drugs in developing countries, improving sanitation and hygiene to reduce risk of infection and disease, using rapid and specific diagnostic techniques to distinguish between bacterial infections and other infections, administrating vaccines and other alternatives to antibiotics, and forming an international coalition for action and a global innovation fund.

Scientists are also pursuing other options to combat antibiotic resistance. Phage therapy, a Soviet era alternative to antibiotics, is being explored with renewed interest to treat particularly stubborn antibiotic resistant infections. It works by using bacteriophages (viruses that infect bacteria) to kill bacterial pathogens, and hinges on a simple principle: that specific bacteriophages will match with and attack specific bacteria until there is no more infection left. Although phage therapy prevents the development of resistance in the bacteria, the treatment has limits because phages can only be used when the exact type of invading bacteria is known. Notwithstanding, phage therapy, along with immunotherapy, ecobiological approaches, and other strategies suggested by the National Institute of Allergy and Infectious Diseases is being pursued with increased vigor.

On our current trajectory, strep throat, C-sections, and scrapped knees will cause unprecedented anxiety. But a comprehensive global initiative can yet stay the coming of a post-antibiotic age. The most monumental scientific achievement of the last century is not yet a failure, and we must do whatever we can to keep it that way.

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