January 15, 2022

Antibiotics are not doing well. We need new ones now

I I cycled to work in a rain storm one day in October 2019. As a longtime cycling commuter, I was not disturbed by the torrents of water as I slid through the puddles of water. ‘water in a hurry. After facing the elements, I was surprised to find a much more severe storm brewing in my own body. Within 24 hours, I felt feverish, it was painful to pee, and I felt the characteristic cloudy urine that signals a urinary tract infection (UTI).

These infections are incredibly common: there are over 150 million cases a year worldwide and most women will experience a UTI at least once in their lifetime. While antibiotics are commonly used to treat them, the ones that do exist become less and less effective as the pathogens that cause UTIs – and all other bacterial infections – become more resistant to them.

The irony is that as a co-founder of a biotech company working to develop a radically new type of antibacterial treatment, I am keenly aware of the growing threat of antibiotic resistance. I can cite statistics on the shocking increase in deaths from drug-resistant infections – the World Health Organization estimates 10 million per year by 2050 – in my sleep. But even with my knowledge, I wasn’t prepared for the year of infection-induced complications and antibiotic failures that lay ahead.

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What I didn’t realize then, but what I know deeply now, is that the development of antibiotic resistance is not the only problem. Our standard antibiotics are bad drugs too: nonspecific, full of side effects, and capable of causing lasting damage. Yet, they are used to treat everyone from infants to the immunocompromised elderly.

A personal odyssey with antibiotics

My journey began with a prescription for the standard first choice antibiotic for UTIs: nitrofurantoin. I took it conscientiously and my symptoms disappeared. Story over, right?

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Wrong. They came back roaring a few weeks later, possibly because a small population of bacteria resistant to nitrofurantoin had survived the treatment and had now recolonized my urethra.

Then came Macrobid, a combination treatment of trimethoprim and sulfamethoxazole. I swallowed the last pill a few hours before presenting the startup I co-founded, Felix Biotechnology, on stage at the international Falling Walls conference. I explained how our approach, using specific viruses – called phages – that infect and kill bacteria, could overcome key problems with traditional antibiotics. I even held up the empty bottle during my presentation to illustrate why we needed new antibiotic treatments.

But even this combination treatment could not clear the infection, and my UTI symptoms continued.

My doctor struggled to find answers and prescribed different antibiotics. But while previous treatments had not worked due to resistance, subsequent cycles presented me with the less discussed and largely ignored problem of existing antibiotics: the devastating side effects. I took amoxicillin plus metronidazole to target Gardnerella in case my symptoms were due to bacterial vaginosis. After three doses, I started to vomit and developed a yeast infection. These side effects are not unusual. Traditional antibiotics are the functional equivalent of a nuclear bomb for the microbiome, destroying pathogens as well as the good ones that help the body function. The problem is, when the good germs are eliminated, the bad ones often crop up and take over.

Even after going through this total microbial decimation, my UTI symptoms returned a week later.

It took a year to finally identify the bacteria responsible for my infection: Ureaplasma, one of the more unusual pathogens that can cause symptoms of UTI. My doctor prescribed another antibiotic for me: doxycycline. After taking only two doses, my face swelled and my throat tightened from the anaphylaxis. This led me to the ER and spent most of December 2020 recovering. In January, the specialist prescribed a fifth antibiotic, ciprofloxacin. It worked wonderfully: within 24 hours my UTI symptoms were completely gone.

The only problem was the rash. It started on day one with an itchy lump on the back of my leg. The next day it had turned into an open, angry sore on the back of my calf. Within three days, it had spread over my arms and legs, turning my skin into a patchwork of oozing sores that itched excruciatingly, only to tear again when touched. I stopped taking cipro and the rash stopped spreading. It healed over the next month, but I still have scars.

After I took – and stopped – cipro, most of my UTI symptoms went away and did not come back. But the pain and discomfort while urinating comes and goes, suggesting that my body is carrying lasting damage. My digestion has also never been the same, with new food sensitivities and intolerances to everything from caffeine to onions. No amount of probiotic food or drink has solved the problem, and I’m not surprised – a small handful of so-called probiotic species are not going to rebuild the rich microbiome of millions of species, built over a period of time. life and lost within a year.

All this for a common infection that is not life threatening. There must be a better solution.

A public health problem

Over the past year or so, I’ve noticed that more and more people are talking about the antibiotic resistance crisis as the next possible pandemic. He sometimes refers to it as the ‘silent pandemic’ because it began long before Covid-19 and will continue thereafter, but has gone unnoticed despite millions of deaths. I am concerned that there will need to be a pandemic disruption to our health care system before significant action is taken.

Tens of thousands of people are currently dying from antibiotic-resistant infections – the death toll compares to car crashes – and even more suffer from the side effects and complications of these drugs. Most of the antibiotics we rely on were developed decades ago and it is amazing that we have put up with them for so long. They lack specificity and decimate the microbiome, leaving people vulnerable to new pathogens. They interact with the body in unpredictable ways, a nuclear option that often makes people sicker instead of helping them get better.

And now we stand to lose even this poor treatment option due to the rise in antibiotic resistance.

This is especially frustrating because the market for new antibiotics is so broken that even drugs and approaches with more specificity and better safety profiles cannot generate a profit, which destroys the incentives for companies to invest. in this domain.

Comparing the R&D landscape for antibiotics to that of almost every other disease is extremely disheartening. Safer and more effective drugs are being developed for common killers like cancer, diabetes and heart disease, and next-generation therapies are being developed for rare and ultra-rare diseases. But when it comes to infections, we’re asked to settle for old, failure-prone drugs.

Fortunately, people are starting to listen. Congress is currently considering two pieces of legislation to address the antibiotic development market: the Law on the Development of an Innovative Strategy for Antimicrobial Resistant Microorganisms (DISARM) (S.1712 and HR4100) and the Subscription Law. Pioneer Antimicrobials to End the Rising Resistance (PASTEUR) (S .4760 and HR8920). Both aim to encourage the development and use of novel antimicrobials and reward businesses and the healthcare ecosystem for doing so.

There is an ongoing debate as to whether either of these bills will solve the deeply flawed antibiotic market, but the most critical thing right now is that we act before we run out of options. And in the process, companies could make antibiotics that not only work, but work better.

Natalie Ma is the co-founder and business development manager of San Francisco-based Felix Biotechnology.


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