The Antibiotic Paradox

What doesn’t Kill you, Makes you Stronger

“Invent a bad antibiotic, and no one will use it. 

Invent a really good antibiotic, and really no one will use it.”  ~  John Rex, Physician

Here’s a dilemma: A patient approaches their doctor presenting some symptoms of a bacterial infection. The solution for an infection would be a simple dose of antibiotic pills. As a doctor, you could either prescribe them with the medication, or not. What would you do? 

In all probability, you decide to give them the pills. And though this might sound like the obvious answer, there’s more to it than just that— the dilemma of whether to frequently use antibiotics is a consequence of the ‘antibiotic paradox.’

Illustrated by Prishi Jain

Since the discovery of Penicillin by Alexander Fleming, scientific breakthroughs in the field of bacterial infections have seen expeditious growth. The drug market had to keep up to sustain its footing in the race. Consequently, Pharmaceutical companies constantly pumped out new and improved varieties of drugs into the market, which benefited the people and the market alike. However, this tale of prosperity did not perpetuate into the second half of the twentieth century. Revenue earned by the firms started to plunge and the pattern of profits began to alter, up to the point where companies started to pull out of the market. But what was the reason?

The only plausible cause that precipitated the present quandary was ‘the antibiotic paradox.’ Identical to the human drive to survive, over time, bacterial microorganisms have been adapting to antibiotic medication and have been growing progressively resistant to them. Stated simply— though antibiotics work to kill bacteria, bacteria (living organisms) are inclined to modify in accordance with the threat to promote their survival; as a result, antibiotics also promote the growth of new strains of resistant bacteria that render older antibiotics obsolete. Therefore, a ‘paradox’ indeed— it was the overuse of largely available drugs in the market that fuelled this resistance to begin with. 

Source: McKenna, M. (2020, August 19). Nature News.

Subsequently, the ‘antibiotic paradox’ has intensified the need for manufacturing and producing newer drugs to combat resistant infections. And although antibiotics boosted the profitability and growth of the most-successful 20th century Pharmaceuticals, the present market has become non-lucrative for them. So the establishments that once dominated the business are making their getaway. Therefore, due to the reluctance to invest, the number of new antibiotics approved for consumption are substantially declining worldwide. 

Furthermore, with large corporations gone, the majority of the firms working on antibiotics are small biotechnology enterprises, who do not have deep-pockets to support the costly endeavour. Hence, in just the past two years, four US Pharma corporations working on antibiotic drugs, declared bankruptcy, despite them introducing an FDA approved drug in the market. Because of this, 5 of the 15 approved antibiotics in 2019— some of which were classified as “essential new medicines” by the WHO—sharply contracted in availability (Jacobs, The New York Times, 2019).

Source: McKenna, M. (2020, August 19). Nature News.

The fast-paced acclimatisation of bacteria causing pneumonia, tuberculosis, and secondary infections in HIV, syphilis and gonorrhoea, amongst multiple others, is resulting in augmenting resistance by the minute. On the contrary, research and development to produce anti-resistant medication has been a process that takes years, if not decades. Since the drug market is closely associated with the health industry, empirical testing, aftereffects of consumption and approval become inexorable components of research and development. Hence, taking 20 odd years to develop, approve and introduce a new antibiotic is not unheard of.

Along with the time-consuming process, the antibiotic business is also a costly affair. Economists in 2016 estimated that solely the identification of an active drug molecule and its approval by the FDA in the United States, cost approximately $1.4 billion (McKenna, Nature, 2020). And to make things worse, WHO revealed that only 14% of all antibiotics actually win approval in the first phase of the research process. 

Moreover, a novel drug isn’t sold as widely to limit the development of additional resistance, and is reserved for dire circumstances only. So even when latest and far-superior drugs are available in the market, the low-cost generic drugs are predominantly prescribed and consumed, making it harder for firms to recoup their investments. Plenty of antibiotic medications also classify as ‘intravenous drugs’ (consumption limited to hospitals), increasing their cost and restricting their availability. This doesn’t help the already strained pockets of small and medium-sized biotech firms, largely working on credit.

The biotech company Achaogen, spent 15 years and $1 billion in developing Zemdri, a drug to treat unyielding urinary tract infections. And despite Zemdri being listed as an ‘essential drug’ the company couldn’t sustain itself. With its stock prices hovering close to zero, and no financing available for marketing, the company declared bankruptcy in 2019. (Jacobs, 2019) And sadly this was the fate of many such small pharmaceuticals. 

Source: McKenna, M. (2020, August 19). Nature News.

A study estimated that it would take around 23 years for any pharmaceutical to procure the smallest amount of profit from a newly developed drug. But the short ‘useful’ life-span of antibiotics until resistant-pathogens develop, poses a hindrance as well. A relatively lower demand for antibiotics due to a shorter 7-14 day treatment periods a few times a year—consumed only when infected, makes the market less-profitable. Especially when compared to markets for long-term chronic diseases like diabetes or hypertension, where medication is a daily necessity. And a new antibiotic would have an even constricted use, since only a limited number of patients (only ones with resistant infections to older meds) would qualify for them.

Thus, unfortunately, far from the profit, the firms are currently not able to cover the basic costs of production in the short run, resulting in heavy losses and bankruptcy. Hence, it is clear that antibiotics are no longer a sustainable source of revenue which is repelling big pharmaceuticals from investing in research of these life-saving drugs. This is especially worrisome since antibiotics are still a “desperately needed class of drugs,” and even more so in the post-covid world. (McKenna, 2020)

Drug-resistant infections caused death in approximately 700,000 cases out of the millions affected until 2020. But because the complications caused by Covid-19 are resulting in a rise in pneumonia and an array of other infections, this number is expected to climb due to the pandemic. The increment in the use of antibiotics as prophylactics, though an unforeseen boom in the short-run, is concerning for the future of the drug market. 

Source: World Health Organization

What is more distressing is that in India, where the infection rates are higher, spread across a larger population and the restriction on drugs are quite relaxed, there is a greater scope for misuse and overuse of antibiotics. Hence, it does not come as a surprise that India not only ranks consistently high in antibiotic use globally, but also produces some of the strongest resistant-strain of bacteria in the world. Nevertheless, though this might be advantageous for Pharmaceutical companies selling generic gold-standard antibiotics like azithromycin, amoxicillin and doxycycline it isn’t sustainable for the long-term health of the market or the population.

This economic conundrum has yet to be untangled. Bearing in mind, human demand for improved medication and the current pandemic, there is an exigency for development in the field of antibiotics. But the costly endeavour is not beneficial for companies in the slightest, since newly manufactured antibiotics are mostly shelved. With no straightforward solution the future of the antibiotic drug market remains uncertain— either the firms would survive or the bacteria would thrive. But what is certain, regardless of outcome, is that the same axiom would apply: what doesn’t kill you, makes you stronger. 

– Sanika Sawant (Editor, Econ Declassified)

References

Boseley, S. (2020, January 17). Big pharma failing to invest in new antibiotics, says WHO. The Guardian. Retrieved from https://www.theguardian.com/business/2020/jan/17/

Hu, C. (2018, July 12). Pharmaceutical companies are backing away from a growing threat that could kill 10 million people a year by 2050. Business Insider. Retrieved from https://www.businessinsider.com/

Jacobs, A. (2019, December 25). Crisis Looms in Antibiotics as Drug Makers Go Bankrupt. The New York Times. Retrieved from https://www.nytimes.com/by/andrew-jacobs 

Langreth, R. (2019, May 3). Antibiotics Aren’t Profitable Enough for Big Pharma to Make More. Bloomberg Business. Retrieved from https://www.bloomberg.com/news/articles/

Laxminarayan, R. and Brown, G. M. (2000). Economics of Antibiotic Resistance: A Theory of Optimal Use. Journal of Environmental Economics and Management 42, 183-206 (2001). Doi:10.1006jeem.2000.1156

McKenna, M. (2020, August 19). The antibiotic paradox: why companies can’t afford to create life-saving drugs. Nature News. Retrieved from https://www.nature.com/

Photo Credit

Orange Pills by Christina Victoria Craft – https://unsplash.com/photos/ZHys6xN7sUE

World Antibiotic Awareness by World Health Organization http://158.232.12.119/campaigns/world-antibiotic-awareness-week/2017/social-media/en/

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