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How to stop the rise and rise of drug-resistant superbugs

By Vanora Bennett

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Modern medicine’s eureka moment

In 1928, scientist Alexander Fleming came back from holiday to find one of his laboratory experiments had accidentally grown mould. The blue-green mould specks had killed the microbial culture he’d been growing. “That’s funny,” he said, and looked more closely. The “mould juice” he deduced must be zapping the microbes turned out to be penicillin. Its development as the most powerful infection-fighting agent the world has ever known has, in the 90 years since, changed the course of history. With the development of a multi-billion-dollar pharmaceutical industry, turning out synthetic versions of this and multiple later antibiotics, people today feel better protected than ever before from disease. In the UK alone, before antibiotics, infectious diseases were responsible for about 40 per cent of deaths a year. Today that figure is just 7 per cent.

Who wouldn’t feel secure? Antibiotics, which attack bacteria, are just one part of a broader set of antimicrobial drugs developed in the 20th century that act against a range of infections. Viruses can be treated with antivirals, fungi with antifungals, and parasites such as malaria with antimalarials. As a result, immense ground has been gained against disease. Advances have been made in the treatment of conditions such as cancer, where antibiotics are crucial in helping chemotherapy patients avoid and fight infection. Surgical procedures such as organ transplants and caesarean sections have become routine and relatively low-risk, thanks to our ability to effectively stave off or treat acute infections with antibiotics. These drugs underpin the miracle of modern medicine.

But not any more.

Dame Sally, Chief Medical Officer for England, issues a stark warning on the dangers of antibiotic resistant superbugs.

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What if the drugs stop working?

In recent years, fears have been growing that our protection against disease is diminishing. More and more cases have been recorded of the bugs that cause diseases we thought we’d conquered becoming resistant to existing drugs. “Superbugs” such as Methicillin‑resistant Staphylococcus aureus (MRSA) lurk in hospitals. Tuberculosis figures are on the rise, as are a host of other diseases.

“I want you to imagine a world where routine surgery, such as caesarean sections, lead to unstoppable and dangerous infections, a world in which sick patients spend years in isolation wards, in which we doctors have no treatments for tuberculosis, no treatments for gonorrhea. Now I know this sounds dystopian, but it’s not the future. This is now. And it’s not just now in far-flung countries. This is now, here in Britain, because infectious diseases are developing resistance to the drugs we use to treat them,” is how England’s Chief Medical Officer, Dame Sally Davies, puts it. “They’re fighting back.”

Take the case of Pamela Bird, a middle-aged British woman who went into hospital in 2011 for a routine operation on her stomach. She fell ill with blood poisoning caused by a resistant bug and has spent years since then on a ward.

 “I’d collapsed in the garden and my daughter found me and I was rushed into intensive care and I were there for 11 days in an induced coma, and it then attacked all my internal organs, so I lost four-fifths of my bowel. Suddenly everybody started wearing blue overalls including porters and anybody else that came near me. You can see people sort of looking and almost covering their mouths to prevent them breathing in the germs cos they don’t know what I’ve got. You’ve got to really work your way through it because it can make you feel very alienated, very isolated. Especially when you’re in a room like this I’ve been for a long time now, one room on your own.”

(3'22') Pamela Bird, a middle-aged British woman who went into hospital in 2011 for a routine operation on her stomach

Also fighting back is gonorrhea, a sexually transmitted disease that once – pre-penicillin - ravaged populations, not only causing painful venereal discharge and other unpleasant symptoms in sufferers but also blindness in their children. “Until recently gonorrhea was quite easily cured by a single pill. But sadly that’s not the case,” says Dame Sally. “Since 2011 in the UK we’ve had to use not one antibiotic but two to treat it and in 2016 we had an outbreak of gonorrhea resistance to one of these two antibiotics spread across the UK. Just a few months afterwards we were told about a patient resistant to both of those drugs. So for that patient we’re out of treatment options. It’s like going back to the pre-antibiotic era.”

AMR: causes, consequences and costs

The World Health Organisation calls this phenomenon anti-microbial resistance, or AMR. This “arises when the micro-organisms which cause infection (e.g. bacteria) survive exposure to a medicine that would normally kill them or stop their growth. AMR has increasingly become a problem in recent times because overuse of antimicrobials has increased the rate at which resistance is developing and spreading but we lack new drugs to challenge these new superbugs. This results in us facing a growing enemy with a largely depleted armoury.”

In our globalised and hyper-connected world, this renewed vulnerability to disease affects everyone.

Right now, a conservative estimate is that AMR claims 25,000 lives in Europe every year. A 2016 study for the British government said that the death toll attributable to AMR around the world is 700,000 people a year.

If there is no decisive action now, the future looks bleaker still.

The World Bank warns that without containment the potential economic and societal costs make it unlikely we will reach the 2030 UN Sustainable Development Goals. Between now and 2050, says a British study by Lord Jim O’Neill, an economist and ex-chairman of Goldman Sachs, the predicted cost of AMR to the global economy is 60 to 100 trillion dollars in lost productivity. That 100 trillion is more than the planet’s current GDP. 

Lord Jim O’Neill, an economist and ex-chairman of Goldman Sachs on AMR on Charlie Rose show

“If by 2050 we’ve not taken action, we’re going to have 10 million deaths a year – and that is more than die at the moment of cancer,” said Dame Sally, who in the past five years has become a leading campaigner against AMR on the global stage.

A problem of human behaviours

The scale of this global problem is so vast that Dame Sally compares it to climate change. Like climate change, she also says, it is caused by human behaviours: by the over-use and improper use of antibiotics in human medicine; by huge-scale use of non-therapeutic antibiotics in the livestock industry and through improperly treated waste from the pharmaceutical industry.  Most of the antibiotics consumed by humans and animals are passed out in urine and faeces.  The release of large amounts of antibiotics into the wider terrestrial, aquatic and marine environment increases bacterial exposure to antibiotics and as a consequence increasing the risks of bacteria developing resistance.

Today’s problems are made worse still by the fact that no new classes of antibiotics have come into clinical use since the late 1980s. Investing in new anti-microbials makes less economic sense for pharmaceutical companies than investing in drugs for chronic diseases.  (Despite high development costs, there is limited scope for a return on investment in developing antibiotics due to the demand for cheap drugs). So it’s stopped being possible to just swap a drug that has become less effective for a new one that works better.

Drug misuse by people

One key cause of AMR proliferation cited by campaigners is misuse of drugs by humans.

The UK government says one in four prescriptions is unnecessary.

In many poorer countries without sophisticated medical systems, antibiotics are routinely bought over the counter without prescription, often from market stalls. Even in southern Europe, despite an EU law which makes it illegal to get antibiotics without a prescription, the over-the-counter figure is 20 per cent. A Google search shows two million results for “buy antibiotics without prescription”. Many are listed by the World Health Organisation as critically important for human health – the sole or limited treatment for a disease. And even people who have never bought an antibiotic may have pressured their doctor to prescribe them unnecessarily. The UK government says one in four prescriptions is unnecessary, creating conditions for resistance to thrive.

Massive use of non-therapeutic antibiotics in the animal farming business

   WHO is recommending that farmers and the food industry stop using antibiotics routinely to promote growth and prevent disease in healthy animals. 

Another driver for AMR proliferation is the large-scale use of antimicrobials in agriculture. Says Dame Sally: “At least two-thirds of antibiotics across the world are fed to livestock and fish, and probably more. And of that, 75 per cent or more is non-therapeutic, non-treatment use, given to healthy animals. Why? To give growth promotion, because it’s cheaper than hygiene - ghastly! - so they get faster from birth to fork. This is illegal in Europe, but, as incomes rise around the world and the amount of meat eaten rises, the amount of antibiotics given to livestock is rising too.”

Penicillin was first used experimentally in farm animals in 1942. Studies showed that hens fed low doses of the drug laid more eggs and sows produced more surviving piglets. “No wonder farmers were so keen,” commented Philip Lymbery and Isabel Oakeshott in their book “Farmageddon: The True Cost of Cheap Meat”. Now, according to Jonathan Safran Foer’s book “Eating Animals”, the scale of factory farming has grown. Six billion chickens a year are raised in factory farms in the EU, over nine billion in America and more than seven billion in China. The worldwide total is 50 billion factory-farmed birds a year – and that will rise exponentially if India and China eventually start consuming poultry at the rate the United States does.

“As chickens, cows and pigs are housed in ever-closer confinement and pushed further beyond their natural capabilities, farmers have grown more and more reliant on antibiotics to prop up the system. This usually involves giving low, sub-therapeutic doses of drugs to animals through their feed or water,” Lymbery and Oakeshott write. “The aim is to compensate for the sickly environment the animals are kept in.”

The first warning sign emerged in the 1960s, with serious outbreaks of treatment-resistant salmonella linked to the poultry industry. It was the first recorded “superbug”. These antibiotic-resistant bacteria can be passed from animals to humans through their meat, or manure, or even in airborne particles.

Raising health standards can, however, reverse the process. In the UK, a scandal over salmonella in eggs peaked in the 1980s, when over 90 per cent of British hens were kept in cages and cabinet minister Edwina Currie famously lost her job for claiming that “most” British eggs were infected. Now almost half of laying hens are either free-range or organic, and salmonella rates have plummeted to 0.25 per cent, with smaller and non-caged flocks much less likely to be infected. Still, in the US, where food production is more highly industrialised, there are around 9.4 million cases of food poisoning every year. Of those leading to hospitalisation around a third are due to salmonella.

Can you do without disease-preventing (rather than disease-curing) antibiotics in animal farming? It clearly makes sense to follow recommendations to “adopt cost-effective, socially agreeable and commercially viable measures to manage antimicrobial resistance in a sustainable manner for live-stock production.” Dame Sally gives the example of Denmark, one of the world’s biggest pork producers, which in 2000 banned antibiotic growth promotion with good results. She also admires Namibia, whose high-quality sanitation and animal welfare requirements – and an antibiotic growth promoter ban – have won the African state the right to export beef to the EU, where antibiotic use for growth promotion has been banned since 2006. “But the catch is that you’ve got to introduce good sanitation and hygiene and animal nutrition, and all those have a cost, and it will be hardest for farmers in the developing world.”

And drug misuse by business

An important third factor in AMR proliferation, as well as human and animal overuse, is manufacturers’ misuse. “We know some manufacturers pump antibiotics into the environment in shocking quantities,” says Dame Sally. “There’s also run-off from high-use hospitals and farms in poor countries. In one river in India, downstream from a manufacturing plant, Swedish research has found about 44 kg of sipefloxicin being released each day – that’s 44,000 doses a day. And what this means is that the river is creating the conditions for super-speed evolution for resistance to critical antimicrobials.”

How do we tackle this?

Hospitals and schools alongside the rest of Khujand are being transformed thanks to clean and accessible water.

While antibiotic use is regulated and relatively low in EU countries, there is less regulation elsewhere. Yet risk-averse states can’t afford to rest on their laurels. Globalisation means the effects of drug resistance are felt everywhere. In a world of easy air travel, it is impossible to quarantine a resistant bug.

First and foremost, the answer is to address the inappropriate use of antibiotics worldwide. “We would argue that global problems require global solutions,” says Dame Sally.

But there are a couple of caveats. It’s not as simple as restricting antibiotic supplies. While use of antibiotics is shooting up in countries like India and China, that’s from a low base. The biggest quantities of antibiotics are still consumed in Australia, America and Europe. So there are issues with international fairness around restricting use, as developing countries which have the highest infectious disease burden might – justifiably - not be willing.

Nor is it enough of an answer to insist that antibiotics are only given out by prescription, in countries where, “if they’ve got next to no medical profession, say in rural areas, or can’t afford a private doctor, then that would be preventing people from getting the medicine they need most.”

England’s CMO prefers a bigger answer – remembering that “antibiotics are not a substitute for sanitation and public health, stopping spitting. Diarrhoea still claims 1.1 million lives each year and is the second most common cause of death in children – and 60 per cent of those lives could be saved by simple access to safe water and sanitation. So we have to invest in sanitation, hygiene, infection control, vaccination and behavioural education.”

It’s also not enough, she underlines, simply to provide technology to help people live more cleanly and healthily. Indian Prime Minister Narendra Modi’s campaign to end the disease-inducing open defecation practised by 70 per cent of Indians living in villages is a case in point. His government built 60 million toilets in an attempt to end the practice. But the initiative had mixed results as many villagers used the new toilets for storage and went on defecating outside. “Tech is not all – we need funding for education in hygiene and behavioural change. Change only happens when everyone is brought on board.”

Lessons to be learned

There are lessons here for investors. It helps to invest (as development banks such as the European Bank for Reconstruction and Development actively do) in high-quality water supply and waste water treatment. It also helps to apply international health standards as well as promote best international practice across the pharma, farming, and all manufacturing investments. And it’s clearly beneficial to promote better animal welfare through recommending the application of EU standards (again something the EBRD routinely does – the only IFI with this written commitment).

There are also initiatives within the grasp of every private individual. Most are easy and personal. One is not to demand antibiotics whenever you have a cold or flu. Another is to slow the spread of germs by washing your hands for 20 seconds, with soap, after using the toilet.

Individuals can also use consumer power for public campaigns to improve commercial practices. A 2016 survey by public health and environmental organisations graded 25 of the largest US fast food chains based on their stance on injecting meat with antibiotics. It found almost all America’s chain restaurants used beef, chicken, and pork routinely treated with antibiotics. Outraged American consumers campaigned successfully to get the brands lagging behind in promising antibiotic-controlled meat to raise their standards. By December 2016, the chain Burger King announced plans to switch to chickens raised without antibiotics “critically important” to human health. In April 2017, the fried chicken fast-food establishment KFC followed suit, and so did McDonald’s in July 2017, promising to phase out the use of high-value human antibiotics in chicken and work on antibiotic plans for other meats, dairy cows and laying hens.

But ultimately it’s governments and global organisations that must write the rules. 

A start has been made. Saving antibiotics for future generations is at last on the global agenda. In 2016, a UN declaration on combating antimicrobial resistance was signed by 193 countries at the UN General Assembly. Signatories committed to develop surveillance and regulatory systems on the use and sales of antimicrobial medicines for humans and animals; encourage innovative ways to develop new antibiotics, and improve rapid diagnostics; and raise awareness among health professionals and the public on how to prevent drug resistant infections.

With the principle in place, it’s now up to individual countries to carry out their promises. The British government includes AMR on its list of medium-term risks, along with flu and terrorism. It’s doing awareness-raising work. It aims to reduce inappropriate prescribing by 50 per cent by 2020.

“We owe it to our children and grandchildren to make sure we have effective antibiotics in 10, 20 and 50 years’ time,” said Dame Sally. “We want the drugs to still work.”

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