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SPONSORED FEATURE : The AMR Conundrum

Sponsored Features Team

The alarm bells are ringing shrilly on the need to tackle anti-microbial resistance which threatens to be the biggest killer in the world in three decades

As foreseen by the father of antibiotics Alexander Fleming way back in 1945, the world now has reached a critical point where the known classes of anti-microbial drugs have little or no impact on the microbes they are meant to destroy.

Globally, thought leaders are worried about the dangers of AMR (Anti-Microbial Resistance). In 2014, then Prime Minister of the United Kingdom, David Cameron commissioned macroeconomist Jim O’Neill to recommend solutions to the problem of AMR. 19 months later, the Review on Antimicrobial Resistance brought out its report.

And the findings are sobering.

But First – What Is AMR?

In layman’s terms antibiotics are the drugs used to kill bacteria. Apart from antibiotics, there are anti-virus drugs which kill viruses and other specific drugs for specific microorganisms.

Microbes reproduce very quickly – in a matter of minutes, in fact. They also evolve very quickly and adapt.

When antibiotics are given to a patient with a bacterial infection, the drugs kill off most of the bacteria in the human body. But there are likely to be a few bacteria which are resistant to that drug. These bacteria then multiply, along with the resistant gene, replacing the original strain that was killed by the antibiotic. Over a period of time, the antibiotic becomes virtually useless as it is unable to act upon the resistant bacteria.

“Antibiotics select out resistant bugs,” explained Dr V Ramasubramaniam, Senior Consultant, Department of Infectious Diseases, Apollo Hospital. He is also in an advisory capacity with the Antimicrobial Stewardship Initiative, a program set up by Indian Council for Medical Research (ICMR).

Dr V Ramasubramanian, Infectious Diseases Specialist
Dr V Ramasubramanian, Infectious Diseases Specialist

“The resistant gene used to be transferred by birth of bacteria – what we call chromosomal mediated – a vertical transfer of genes which sit within the nuclei of the bacteria. But now the bacteria are becoming smarter. The resistant gene is available in the cytoplasm itself, so the transfer can now be across species. As the bacteria move through one another, they can transfer the resistant gene to a completely new species of bacteria – this is what we call plasmid mediated. This is a horizontal kind of transfer. All microbes are increasingly becoming resistant to several classes of antibiotics now,” he adds.

“This has led to the emergence of ‘superbugs’ such as Methicillin-resistant Staphylococcus aureus (MRSA) and extremely drug-resistant tuberculosis, bacteria which are difficult or impossible to treat with existing medicines,” according to the 2016 Jim O’Neill report.

Increasing resistance to antibiotics across the world Source: World Economic Forum Global Risks Report 2013
Increasing resistance to antibiotics across the world Source: World Economic Forum Global Risks Report 2013

The report goes on to warn that AMR could take 10 million lives every year by 2050 if its spread is not stemmed. Currently around 700,000 deaths across the world are due to anti-microbial resistance.

How Does AMR Spread?

The question of how AMR has become such a global crisis can be answered in a three-fold manner. Overuse of antibiotics in humans, overuse of antibiotics in the meat, poultry and fish industry and overuse of antibiotics in agriculture.

“There is phenomenal misuse and abuse of antibiotics,” says Dr V Ramasubramanian. “Two-thirds of antibiotics taken by humans are inappropriate.

For instance if a patient comes to a doctor with low blood pressure, difficulty in breathing and fever, it could be sepsis, a condition that requires antibiotic treatment. It could also be something else altogether which does not need antibiotics. But the presenting symptoms are the same. How does the doctor decide? To be on the safe side, he prescribes antibiotics to the patient.

At the same time, we also have patients coming in with a flu or a common cold and demanding antibiotics from the doctor. This comes from a culture of instant gratification, but it leads to overuse of antibiotics,” he adds.

The problem is present across the world.

According to the Jim O’Neill report, more than actual human consumption of antibiotics, it is the ingestion of antibiotics through food that increases the spread of AMR.

Antibiotics used in food industry poses a greater risk to humans Source: World Economic Forum Global Risks Report 2013
Antibiotics used in food industry poses a greater risk to humans Source: World Economic Forum Global Risks Report 2013

Antibiotics are used with abandon in the rearing of chicken, cattle, goats and pigs for food. In an effort to ensure that the animals, kept in small and close quarters, do not fall ill and spread infectious diseases that could cull the entire herd, antibiotics are fed along with their regular feed as a preventive measure.

“The quantity of antibiotics used in livestock is vast. In the US, for example, of the antibiotics defined as medically important for humans by the US Food and Drug Administration (FDA), over 70 percent (by weight) are sold for use in animals. Many countries are also likely to use more antibiotics in agriculture than in humans but they do not even hold or publish the information,” according to the 2016 O’Neill report.

“Less than 20% of antibiotics are consumed by humans,” said Dr Ramasubramanian. “70-80% of the antibiotics are used in poultry, cattle and fish as growth promoters. Cooking the meat can remove most of the resistant bugs, but one cannot say for sure if it is completely gone. And if the raw meat is placed in the kitchen or on tables, knives are used, that means your kitchen is already contaminated,” he says.

He says that AMR can affect a person without that person even consuming antibiotics. “Antibiotic resistant bacteria from a person’s gut goes through the sewer lines. At some point, due to the poor state of sanitation infrastructure in our country, the sewer lines mix into drinking water lines. In this manner, antibiotic resistant drugs can affect an entire community,” he says.

Lack Of New Drugs

Compounding the issue is the fact that the last known class of antibiotics was developed in 1987 – the lipopeptides! No major new antimicrobial drugs have been discovered in the past almost three decades.

No new classes of antibiotics have been discovered since 1987 Source: World Economic Forum Global Risks Report 2013
No new classes of antibiotics have been discovered since 1987 Source: World Economic Forum Global Risks Report 2013

“According to a 2016 study by The Pew Charitable Trusts, every currently available antibiotic is derived from a class discovered by 1984,” records the World Economic Forum’s Global Risks Report 2018.

The reason for this is that it is more profitable for pharmaceutical companies to invest in making drugs to treat ailments like cancer rather than antibiotiocs and antivirals where profit margins are small.

For instance, according to the O’Neill report, the total market for antibiotics is around USD 40 billion a year. Only USD 4.7 billion of this though is from the sales of patented antibiotics. This is equivalent to the annual sales of one single cancer drug. No profit, no antibiotic.

The O’Neill report goes on to record how the profit-seeking pharmaceutical industry has turned away from the interests of medicine to other non-communicable diseases like cancer, thereby weakening us in the battle against AMR.

The Effects

So what happens if we sit back and allow AMR to spread? We lose in a variety of ways. Take for instance a surgery – a Caesarian delivery, for instance. The mother is kept free from infection by the use of antibiotics, thereby ensuring her quick recovery and good health.

But if antibiotics stopped working, even such small surgeries could turn fatal. Chemotherapy for cancer treatment could become life threatening.

“Nearly 200,000 people die every year from multidrug-resistant and extremely drug resistant tuberculosis (TB) alone. In India, antibiotic-resistant neonatal infections cause the deaths of nearly 60,000 new-borns each year,” writes Jim O’Neill in the 2016 report.

Another example is that of gonorrhoea which is down to its ‘last line’ antibiotic. Once this too becomes redundant, there is no cure.

Another danger is that doctors, left with no options, are now using antibiotics that have been thus far avoided due to the bad side effects of the drug. “This is the case with colistin, for example, which can cause kidney failure and so was never given to patients for many years. Over the past decade however, it has re-entered use as a last resort treatment for patients with particularly hard-to-treat Gram-negative bacterial infections, and already colistin resistance is emerging,” warns the O’Neill report.

The economic impact of AMR on countries is already showing. The US, for instance, is coughing up an additional USD 20 billion every year to treat two million infections caused by bacteria which have already become resistant to the first-line antibiotics, says the report.

The global AMR conundrum Source: World Economic Forum Global Risks Report 2013
The global AMR conundrum Source: World Economic Forum Global Risks Report 2013

“India, with more than 20,000 hospitals, more than a billion population, wide cultural diversity, socio-economic disparity, and a large medical community of more than three-fourths of a million doctors, will find the resistance problem an issue very difficult to tackle unless we initiate whole hearted and joint efforts to tackle the menace on a war footing,” stated doctors and healthcare policymakers at a seminar on AMR called “The Chennai declaration: A roadmap to tackle the challenge of antimicrobial resistance” held in 2013.

The Way Forward

The Doomsday prediction is almost upon us but a global concerted effort could slow the spread of AMR.

This can be done by spreading awareness about AMR the world over, using antibiotics sparingly in humans, animals and agriculture and by developing new drugs.

The Jim O’Neill report estimates the cost of global action on all these fronts at USD 40 billion over a 10-year period.

Of this, says the report, about USD 16 billion would be needed to overhaul the R&D pipeline.

Restricting the sale of over-the-counter antibiotics is also one way to tackle the problem – by forcing sales of these drugs only through the prescription of a doctor.

But there are hurdles here as well, especially in the developing nations. As pointed out in the World Economic Forum’s 2013 Global Risks Report – “A national task force in India recommended the end of over-the-counter sales of antibiotics, but India’s Health Minister responded with concern that such a move would effectively deny access to antibiotics to patients in rural areas where there are no physicians to prescribe the drug.”