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14 Sep 18 08:02

A few years ago, I went to the pool. I must have had a little cut somewhere on my big right toe. Two days later the toe doubled in size. Walking became nearly impossible and a red rash developed, separated from the other areas of my skin by a thin red line. 

Unable to fit my foot in a shoe, I stumbled to the doctor. The diagnosis: I had gangrene. He gave me a big dose of antibiotics and told me to keep my leg raised. If there was no improvement within 24 hours I would need to go to hospital.

I went home, took the pills and fell asleep. I woke up covered in red polka dots. Back to the doctor. I had developed an allergy to the drug. We had to switch to another antibiotic, which finally worked. Five days later, my gangrene was history. Still, doctors at that time told me, if the antibiotic hadn't worked, I could have lost my foot and potentially my life.

I was reminded of this experience, when I attended an expert conference on antibiotic resistance. Unfortunately, at the conference, I heard that a scenario like mine will become more commonplace as bacteria become more and more resistant to antibiotics. As someone who has allergies to some antibiotics, I am one-step closer to fight bacterial infections on my own. A bleak outlook for me – and for you.

Bacteria – smarter and older than us

Bacteria has been around since almost the beginning of life on earth – 4 billion years roughly, give or take a couple of hundred million years. They conquered any environment on earth – the highest mountains, the deepest oceans, even solid rocks. They also conquered us - or better instrumentalised our bodies for their survival. They live in our guts, on our skin. One hypothesis even states, that the power stations of our cells – the mitochondria – are actually bacteria that were smart enough to make their home in the protected realm of our cells.

Of course, the relationship is both give and take. For example, they supply us with enzymes to digest our food so we can survive. In turn, we offer them a habitat. So far so harmonic. But once in a while we encounter a bacteria we are not used to. And this can threaten our lives – like the one which triggered my gangrene.

Antibiotics – the double-edged sword

Gangrene was the nemesis of humans since the dawn of history. In the American Civil war, it killed nearly half of those infected. While treatment improved the survival rates slowly over time, cure was only possible once antibiotics arrived on the scene.

Some hail it as the biggest human discovery of the last millennium. And for once the claim may not be an outrageous one because many of us would not be around, if not for penicillin and its followers.

In 1945, Alexander Fleming, who won a Nobel Prize that year for his discovery of penicillin, warned that misuse of the drug could result in selection for resistant bacteria. True to this prediction, resistance began to emerge within 10 years after the wide scale introduction. The arrival of antibiotics was our blessing - and our curse at the same time.

The rise of the resistance

In some parts of the world, lack of health insurance coverage forced governments to sell antibiotics over the counter without prescription. The subsequent self-medication by consumers made the situation even worse. But the real killer to stopping the tide of resistant bacteria was livestock farming.

Today, we use 131,109 tons of antibiotics per year. Two thirds of which is being used on animals. If you give 500 mg per day to an animal you can treat roughly 475 million animals per day with antibiotics. Modern livestock farming quickly became the largest industrial producer of antibiotic resistant bacteria in the world. Carry them from the farm to the hospital and you quickly have the perfect public health storm.

A silent battle with day to day casualties

In 2013 the Center for Disease Control and Prevention published a report: "Antibiotic resistance threats in the United States, 2013". The numbers were sobering: over 2 million people per year got ill due to antibiotic resistance and 23,000 people lost their lives. For a specific bacteria you could add another 250,000 people falling ill and a further 14,000 dying. At that time it was estimated that resistance added in excess of USD 20 billion to direct health care costs, with additional costs to society for lost productivity as high as USD 35 billion a year. That's the new normal. I checked the numbers – they have not change a lot in the last four or so years. By comparison, the US meat industry generated total revenues of US$198 billion in 2013.

Pondering over this dystopian picture, another question came into my mind. What if a bacterium is not only resistant to most antibiotics and easily transmissible but also has a long incubation period allowing it to travel the world before the impact becomes apparent?

This is the scenario many experts are afraid of. It would trigger a pandemic battle on a global scale.

Going to war without ammunition

If this happens, we will be in a public health war with no ammunition. This is what I learned listening to one expert after another stepping to the dais to speak to us. The antibiotics we have simply won't work in such a scenario. And we don't have anything else up our sleeves, because there is just no money for developing what we need.

Big pharma does not do antibiotics

First of all, research costs money. Secondly, antibiotics' use comes with strict restrictions so you can't do a "mass sell". If taken, and effective, they heal a patient within days. Consequently, repeat sales are often not possible. Recouping the cost of development and generating a profit would make antibiotics excessively expensive. The result is that our antibiotics development pipeline is empty. There is currently only one exception, and that one is still in clinical trials. So what shall we do?

We need to buy ourselves time. First prescription practices for antibiotics must change. Even the WorldTrade Organization has lined up with the WHO to argue the case for application reductions.

While stopping short of calling for a stop of antibiotics use without prescription for animals and humans the paper points in this direction, when you look at the overall context. Reducing our usage will buy us time until the "epidemic super-bug arrives". We can see that in countries with restrictive prescription practices. The have much lower occurrences of resistant strains than those with a liberal regimes. In addition, if prescription and distribution were tightened, resistant strain numbers would go down.

So making antibiotics prescription-only again is an important step. But we have to do more. Regulating internet pharmacies, which distribute antibiotics with almost no supervision at all, is a must. Doctors should also curtail prescribing antibiotics to stem the tide of resistance development.

Supplementing the actions above with more funding for hospital hygiene will also help combat resistance. In countries with less developed health systems, the return on investment of these activities is much higher than spending money on drug development. Still, these actions alone won't protect us. In the end, we know a new super-bug will arrive and to fight it we need new antibiotics.

It's all about the money

The conference closed with a discussion open to the general public. After keynote speeches introducing the topic, the question on why the pipeline is empty came up. The explanation was that the private sector will pump its research billions into the next cancer, arthritis, cholesterol, and blood pressure drugs, therapies that patients need to have for decades (assuring big revenues).

Antibiotic development is reliant on donations from institutions like the Gates Foundation and some government grants. The money available is at best in the three-digit million-dollar range – nothing when you look at what is available in the private sector to develop drugs for other uses.

Sometimes it seems you need the state

At the end there was a public vote on four antibiotic development funding proposals. Trust the private sector to come in if the need arises, rely on foundation and government grants, pay research out of taxes, or tax pharma revenues to fund the research.

Taxing pharma was the most popular option by a significant margin. Will this ever happen? I have my doubts. Still, if society would endorse this, it would at least get us somewhere.

This autumn, the United Nations will assemble in Geneva to discuss funding of antibiotic research with the private sector. Given where we are, I wonder if we are already too late.

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1 Comment

Bernd Wilke - 16 Nov 2018, 12:06 p.m.

Dear both, thanks for the comments:-)

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