Antibiotic Armageddon

Antibiotic Armageddon

Some experts say we are moving back to the pre-antibiotic era. No. this will be a post-antibiotic era. In terms of new replacement antibiotics, the pipeline is virtually dry. A post-antibiotic era means, in effect, an end to modern medicine as we know it.

Dr. Margaret Chan, Director-General of the World Health Organization

Antibiotics might not seem as pressing as global terrorism or healthcare reforms. Bacteria don’t even, seem that scary. You can’t really see them, and yes there’s a scary Mission Impossible movie every now and then. But really, the worst experience most of us have from bacteria, is a bit of food poisoning.

Truth is, antibiotics are almost single-handedly the biggest saver of human life that we’ve ever come across. Today you can cut yourself, get an infection, even have surgery, comfortable in the knowledge that antibiotics will take care of you.

Antibiotics saved America

In 1999, a review in the Journal of the American Medical Association found that since 1936 - when widespread antibiotics were introduced into the US - the death rate dropped by 220 people (per 100,000) in just 15 years. In other words, just in the US, 8.2 % less people were dying every year. For 15 years. The authors of the report note that

Pneumonia and influenza were responsible for the largest number of infectious disease deaths throughout the century. Tuberculosis caused almost as many deaths as pneumonia and influenza early in the century, but tuberculosis mortality dropped off sharply after 1945.

Forget about wars. 3 diseases, 2 of which bacterial, were killing more Americans. Then, almost overnight they were written off into the history books.

By comparison, all other healthcare advances in the next 45 years, combined, only reduced the death rate by a further 20 deaths per 100,000.

By the start of the 1960s, the US surgeon general was so confident in antibiotics that he even declared that “infectious disease is conquered”, making hospitals like this a thing of the past.

Typus hospital

Today’s reality

What happened to that euphoric optimism of the 60s? Why are we now facing what many call an apocalyptic scenario?

Let’s start by looking at the numbers. In Europe, 25,000 patients are dying every year in hospitals as a result of bacterial infections that are antibiotic resistant. In the US, the CDC estimates the number at 23,000 patients/year.

Reports suggest that by 2050, that number will have risen to 100 million people/year dying globally from antibiotic-resistant bacteria. Surpassing even cancer as the biggest killer in the world.

But none of this is new. The problem is that a few sick people in hospitals doesn’t make good headlines. For example, I myself have written before about how cholera on the tiny, island nation of Haiti is 3x deadlier than everything ever conducted by ISIS.

News from China

What is new, is this week in China a strain of Enterobacteriaceae has been found resistant to polymyxins.

In itself, that sounds like a really boring, sciencey sentence. So let me take a moment to explain why this is really, really scary.

Enterobacteriaceae is a family of bacteria (E. coli being the most famous), and a pretty big one at that - think of them like insects. Enterobacteriaceae is a family of bacteria that, like insects, are pretty much everywhere. You have them, right now on your skin, in your gut,  in your food, everywhere. They are responsible for food poisoning, blood infections, pneumonia and more.

Polymyxin, meanwhile, is just a fancy name for a small group of antibiotics. Polymyxins are actually over 60 years old and one of the oldest known antibiotics, but they are rarely used because they are pretty toxic. Exactly because they are so toxic, we haven’t  used them in hospitals for decades. Who’s going to pick the horrible side effects when non-toxic  alternatives exist, right? 

As this group of antibiotics haven’t been used in hospitals for years, the bacteria in hospitals don’t have much in the way of defence to them. For this reason, the World Health Organization classified polymyxins as “antibiotics of last resort”, basically meaning they were the last hope, and not to be used in hospitals for as long as possible.

Antibiotic plates

Nobody told the farmers

Unfortunately, nobody told farmers. Our hospitals might not have been using polymyxins in humans, but pig farmers have been using them routinely for years.

Intensive farming requires as many animals, from as few resources as possible. For a farmer, it is much easier and cheaper to have a large number of pigs in a small space. The problem is that when you put a lot of animals into a really confined environment, disease spreads like wildfire. For the farmer, disease means that the animals don’t grow or worse still they are not fit for human consumption. To prevent disease in the first place, and therefore, making sure the farmer gets to sell the animals, intensive farming routinely feeds the animals antibiotics for their whole life.

Constantly exposing animals to antibiotic is great for the farmers. Darwinian evolution, however, teaches us that where you put a selection pressure, mutation shall arise. In this case, by constantly feeding the pigs antibiotics, you are creating an artificial environment where bacteria, with immunity to that antibiotic, would suddenly have a huge advantage.

Unsurprisingly then, scientists have just found E. coli in pig farms that are resistant to polymyxin antibiotics.

This is really bad news.

EM of E. coli

From bad to worse

The researchers first found polymyxin resistance in E. coli taken from a pig in Shanghai. Knowing this was bad news, they started to investigate the type of antibiotic resistance.

They found the resistance was coming from a new gene, mcr-1 (scientists make the catchiest names). What worried the scientists was that the gene was found on a plasmid. Bacteria, like E. coli, have 2 types of DNA, the first kind is like the normal stuff we think about in animals arranged into a sort of nucleus. The second kind are called plasmids, they are little rings of DNA they exchange with one another during bacteria sex. This new antibiotic resistance gene was on a plasmid. Which means that the bacteria could quickly spread the resistance amongst themselves during bacteria sex, as well as swap it with other species really easily.

Lab tests

Knowing that the antibiotic resistance could be transferred easily, the researchers quickly expanded their survey. They collected bacteria samples from pigs at abattoirs across four Chinese provinces. Then from pork and chicken sold in 30 open markets and 27 supermarkets across the city of Guangzhou (near Hong Kong). Finally, they looked at bacterial samples from patients with infections at two hospitals.

They found the antibiotic resistance gene in 166 out of 804 animals tested. In 78 of 523 raw meat samples. But most worryingly, they found it in 16 E. coli and K. pneumoniae (the bug normally responsible for pneumonia) samples taken from 1,322 patients.

In short, the antibiotic of last resort is already useless. There are patients, in hospitals, with infections that are already resistance.

The antibiotic has not been routinely used in hospitals for decades and already antibiotic resistance is jumping species and infecting hospital patients.

Darkest before the dawn

The demand of polymyxin from agriculture is expected to reach 12,000 tonnes/year by the end of the year and looks to be expanding. The authors of the report write,

There are many countries, including in Europe, that use polymixins in agriculture, and therefore the responsibility to acknowledge and address the use of antibiotics across human and veterinary sectors must be also global

This is not the first time that polymyxin resistance has been demonstrated in the scientific literature, but it is the first time that it has been shown to be transferable in the same, and between species.

We need world thinking

Perhaps an obvious first step would be to reduce or stop the use of polymyxins in agriculture. By removing the antibiotic from farms, with time, the need for the bacteria to carry the antibiotic resistance gene would cease. However, the Chinese researchers already thought of this. They showed that the bacteria clung onto the gene long after the antibiotic is removed.

Again and again, we’ve seen swine flu, bird flu and others emerge from such farming conditions. Every time, it risks global health…and then nothing happens

A better solution would be to change farming practices. If factory farming didn’t hold animals so closely together, they wouldn’t need antibiotics because they wouldn’t get sick the same.

Current farming is short-sighted and dangerous to human health. Again and again, we’ve seen swine flu, bird flu and several other disease emerge from such farming conditions. Every time, it risks pandemics and global health, shuts airports, creates quarantined hospitals, kills innocent people, and then nothing happens.

As more of the world is routinely eating meat, farming production has become more economical. Even ignoring animal cruelty concerns, the reliance on antibiotics will continue to risk global health. This is a global problem. Remember, bacteria do not concern themselves with lines on a map. 

Medicine and money

This is a problem that we need to think about now. It might seem that a world without antibiotics wouldn’t be so bad. After all, when was the last time you took any? But, antibiotics protect the most needy, in their toughest moments. Without antibiotics, we return to a world without surgery, a world where childbirth routinely kills, a world where chemotherapy and cancer are death sentences. A world where few people actually walk out of hospital.

The solution is in economics

Ultimately, the antibiotics problem is an economic one. In the developed world, antibiotics were a cheap, sometimes lazy, solution for many doctors and the over-prescription of antibiotics have unquestionably caused problems. This is changing. In the developing world, antibiotics that could make a difference, are often not prescribed enough, because they are too expensive. This means we live in a world that still has diseases like tuberculosis.

Even if they succeed, the potential profit is tiny because a new “antibiotic of last resort”, ideally, is never used.

Drug companies show no interest in developing new antibiotics. Most have already closed their development facilities. The cost of development is hugely expensive and high risk. Then, even if they succeed, the potential profit is tiny because a new “antibiotic of last resort”, ideally, is never used.

Meanwhile, antibiotic resistant bacteria are a living nightmare for many doctors. Infections greatly increase the amount of time patients need to stay in hospital, and will inevitably kill some.

The main source of antibiotic resistant bacteria is intensive, livestock farming. Livestock farmers are only responding to demand, and in a competitive marketplace, who can blame them? There is a sudden, huge global demand for meat, and to maximize their yields means they will use antibiotics.

We cannot expect farmers to abandon antibiotics out of the goodness of their hearts. Not in a free market. Not when the demand for cheap meat is so high.

Antibiotics is a global crisis that, like climate change, requires global solutions. Only with a global shift toward livestock grown organically, without the use of antibiotics, will the crisis ease. It is my concern, that only a truly horrible disease akin to bovine-TB or foot-and-mouth, will make the choice for them. Only when farms are burning thousands of animals, across entire nations, will the world start to take notice.

Foot and mouth farm burning

A post-antibiotic world

What does a world after antibiotics look like? Some imagine a world where healthcare returns to start of the 20th century - a place where a simple chest infection requires a year in hospital and probably kills. Some researchers take a more optimist view.

Perhaps in a world without antibiotics we are forced into using more sophisticated weapons. Current antibiotics are known as “broad spectrum” that is, they attack everything at the same time. Much like a bomb doesn’t care what is underneath it. This is why it’s common to have stomach upsets after antibiotics. The antibiotics also kill all the “good” bacteria inside of your gut.

Use their own weapons against them

Focus for some years has been on developing “narrow spectrum” antibiotics - those that have a very sharp focus, i.e. selectively targeting only one or two types of bacteria. This targeted approach is seen most effectively in bacteriocins - agents that kill a bacteria, I personally did my PhD on bacteriocins. Typically they are a bacteria’s way of killing other bacteria. A useful trick when times get tight and there’s too much competition. Obviously, the key to a good weapon is not killing yourself in the process. So these weapons are very good at targeting one type of bacteria while leaving the other ones alone.

For a long time, most researchers thought that bacteriocins would never make a useful clinical strategy. Mostly because injecting a person with foreign material from bacteria would cause an immune response that would destroy the stuff you just injected.


However, data still coming out of the lab looks like in animal testing there is not an immune response. Even if bacteriocins were outright rejected by the immune system, protein engineering is also showing good progress. With some clever engineering it might be possible to combine the selective killer part of the bacteriocin with a human part to make an engineered hybrid that “looks” human enough to survive in the body.

These tools are looking promising, but they provide no guarantee. No guarantee that they will work or, that they arrive in time.

Keep developing antibiotics

In the shorter term, researchers and industry must be encouraged to keep developing new antibiotics.

The international group, the Review on Antimicrobial Resistance recommends the establishment of an innovation fund that would guarantee companies a return on any new antibiotics they might make. It hopes that this fund could produce 15 new antibiotics in 10 years, but that requires $2 billion, talented scientists and time.

Thanks to antibiotics, myself and millions of others, have been able to live safe in the knowledge of getting better. As antibiotic resistance continues to become a bigger and bigger problem, our progress seems to be going backwards.

Without dedicated, global efforts, the hope that we’ll get better after disease will be taken away.

That won’t happen unless scientists push this forward and make this an issue that people pay attention to.

This page has previously appeared on previous versions of morganbye.com1 2

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