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Antibiotics – a class of drugs commonly used in modern day medicine and designed to selectively target and kill disease-causing microbes – are postulated to have saved millions of lives but are also becoming increasingly ineffective due to the rise of antimicrobial resistance. To stop the spread of superbugs, a truly unified response from the global population is necessary

By Channy Lee

Sir Alexander Fleming warned of bacteria becoming resistant to penicillin in 1945 when he accepted the Nobel Prize for his discovery of the first commercialized
antibiotics. Antibiotics, a class of drugs commonly used in modern day medicine and designed to selectively target and kill disease-causing microbes, are posing a worldwide challenge larger than what Fleming had cautioned. That is, the existing family of antibiotics is becoming increasingly ineffective in the fight against bacterial infections.

In 2013, it was estimated by Centers for Disease Control and Prevention (CDC) that more than two million people fall ill every year with antibiotic-resistant infections in the US, causing at least 23,000 deaths. The number of deaths puts to foreground the critical case of rising antibiotic resistance, which is classified as the ability bacteria develop over time to overcome the pathogen-malignant effect of antimicrobial agents.

The market for this essential class of drugs is part of a larger problem. The pipeline for antibiotics is, in effect, gradually turning obsolete because few new antibiotics have proved to be an effective alternative and even fewer have been approved for the greater market in the last 30 years. After 70 years of birth of the revolutionary medicine, the healthcare industry – and governments worldwide – stands before a race against fast-adapting bacteria.

A post-antibiotic era?

The discovery of antibiotics is postulated to have saved millions of lives. The medicine has enabled the progress of treatment and surgery with preventive measures of disease-causing infections, promoted stable growth in livestock animals, while significantly reducing the possibility of an epidemic outbreak. It remains a weapon of choice among healthcare professionals in the fight against bacterial infections – and will be so in the foreseeable future.

The use of antibiotics, however, has continued to expand in ways that critics say are having a negative impact on the pharmaceutical effects of the drug and are leading to the rise of antimicrobial-resistant bacteria. Viruses or bacteria developing resistance to drugs is a natural phenomenon, but the case of antimicrobials, namely antibiotics, has been greatly exacerbated by a plurality of misuse and overuse.

According to a study conducted by CDC, a total of 262.5 million courses of antibiotics were prescribed for outpatients in 2011, which is equivalent to 842 prescriptions per 1,000 people. Being so familiar with a drug prescribed so often, many demand antibiotics as a form of treatment for virus-induced illnesses, such as a cold or a flu, for which antibacterial compounds are useless.
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Antibiotics are optimally prescribed only in 50 percent of the time, and even when prescribed properly and accordingly, many patients have a tendency to stop taking the drug when they feel better. They can lead to the growth of antibiotics resistance in patients and the spread of resistance strains. In some countries, access to antibiotics is simply too easy because they are commercially available over the counter, exposing the drug to potential abuse.

Inessential use of antibiotics also prevail across livestock raising, with hundreds of animals being fed with antimicrobial-administered food or through direct injection in animal husbandry. Pervasive acceptance towards such practices has contributed to the emergence of a threat to public health alongside the danger arising from overconsumption of antibiotics among humans.

Gonorrhea and tuberculosis, for example, used to be diseases that could be cured in a few days with antibiotics. It is no longer the case as antimicrobial resistant genes continue to spread among strains of bacteria because the constant use of antimicrobials can fundamentally alter microbial ecosystems of humans.

As a result, microbes began to fight back for survival in a natural selection process and are now winning by out-doing the arsenal of medicine. Strains of tuberculosis completely drug-resistant that emerged in India a few years ago have now been identified worldwide.

A vicious cycle

Fundamentally, reducing misuse and overuse of antibiotics in human medicine and food production is one way to alleviate the drugs’ declining effectiveness. The need for containment of antimicrobial resistance has been recognized decades ago on a global scale, as evidenced by the Resolution of the World Health Organization (WHO) in 1998, which urged member states to formulate appropriate measures to tackle antimicrobial resistance.

There are multiple dimensions as to why the historically stable and effective use of antibiotics is failing. Resistance is a problem on its own, and the fact that there are few alternatives once resistance renders existing antimicrobial agents no longer reliable has expanded the battle against antimicrobial resistance beyond the realm of bacteria and drugs themselves.

From 1983 to 1987, there were 16 new antibiotics approved by the US Food and Drug Administration. From 2008 to 2012, only three were approved. More than 20 large pharmaceuticals had programs to develop new antibacterial agents twenty years ago. The number was down to four in 2013. Researchers have even noted a diminishing supply of existing drugs, although still far from a critical point.

When it comes to antibiotics, the drugs are not working and neither is the market, partly due to a larger focus on drug development for anti-viral infections and other diseases. The commercial valuation of any new antibiotic is tricky because of the uncertainty a drug may involve. Plus, it is harder to estimate actual future demand for antibiotics than those for other long-term drugs targeting, for example, cancer or heart diseases.

The investment on developing new antibiotics is risky business because drug resistance may emerge any time after they are introduced to the market. The financial burden of research and development, in terms of resources and time, is immense. On average, it takes 23 years for an antibiotic development to realize some return on investment, according to estimates by the UK Review Committee on Antimicrobial Resistance.

The paradox in establishing a sustainable supply of antimicrobial agents is: there must be enough demand and purchases just to offset the development cost and help fund R&D of the next-generation antibiotics; yet, there must be minimal use of the drug in order to extend its effectiveness and to prolong shelf-life before resistance develops again.

The good news is: governments are getting involved. British Prime Minister David Cameron in 2015 appointed former Goldman Sachs chief economist Jim O’Neill to head the UK Review Committee on Antimicrobial Resistance – to specifically devise a comprehensive plan to tackle the issue of antimicrobial resistance. The consensus is that the world market needs a fix to steer away from the direction headed towards a global epidemic.

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Racing against the clock

No new major class of antibiotics has been discovered since 1987, according to WHO. In spite of a pessimistic outlook, there are indications of new approaches to the development of a class of medicine deemed so vital in the fight against bacterial infection in the human body. Some involve looking back to precursors of modern day treatments that served the same purpose prior to the discovery of antibiotics, and microbiology is an entirely new approach to the objective.

Then, there are the proposed solutions leveraging economic means – close to 100 pharmaceutical companies and trade associations at the World Economic Forum in Davos earlier this year issued a joint statement urging more action on the governmental level to incentivize development of new antibiotics. Public-private partnerships have since been surfacing, and governments across the globe have issued plans to drive research and development for new antibiotics.

De-linkage is another economic option being proposed by economists, where profitability would be ‘de-linked’ from volume of sales. Although controversial, it may prove useful “given the difficulty in significantly curtailing use, [the] incentive for drug companies to sell more drugs, and weak market incentives for private companies to undertake research into areas that society needs but are not profitable. Translated into a procedure, one or several lump sums would be paid to the developer regardless of how many courses of drugs are sold.”

The World Economic Forum has identified antimicrobial resistance as a global risk beyond the capacity of any organization or nation to manage or mitigate alone. At the World Health Assembly in May 2015, a global action plan on antimicrobial resistance was adopted, outlining five objectives in an approach that requires coordination among numerous international sectors and actors. It is set to acknowledge the importance of securing a sustainable pipeline for replacing drugs that are no longer effective.

To stop the spread of superbugs – bacteria which have become resistant to antibiotics typically used to combat the microbe – it is yet to be clear which solutions will be sufficient to compensate for the circumstances of reduced economic incentives and strenuous regulatory requirements. The crisis therefore is not just a convoluted challenge posed on the healthcare sector, but calls for a truly unified response from the global population.