I biked to work in a rainstorm one day in October 2019. As a longtime bike commuter, I was unfazed by the torrents of water as I skidded through puddles in a rush. After facing down the weather, I was surprised to find a far more violent storm brewing in my own body. Within 24 hours I felt feverish, it hurt to pee, and I experienced the characteristic cloudy urine that signals a urinary tract infection (UTI).
These infections are incredibly common: there are more than 150 million cases a year globally and most women will experience a UTI at least once in their lives. While antibiotics are routinely used to treat them, the existing ones are becoming less and less effective as the pathogens that cause UTIs — and every other bacterial infection — are becoming more and more resistant to them.
The irony of the situation is that, as the cofounder of a biotech company working to develop a radically new type of antibacterial treatment, I am acutely aware of the growing threat of antibiotic resistance. I can quote statistics about the shocking rise in deaths due to drug-resistant infections — the World Health Organization estimates 10 million per year by 2050 — in my sleep. But even with my knowledge, I was unprepared for the year of infection-induced complications and antibiotic failures that awaited me.
What I hadn’t realized at the time, but what I am deeply familiar with now, is that the evolution of antibiotic resistance isn’t the only problem. Our standard antibiotics are also bad drugs: nonspecific, rife with side effects, and capable of causing lasting damage. Yet they are used to treat everyone from infants to the immune-compromised elderly.
A personal odyssey with antibiotics
My journey began with a prescription for the standard, first-choice antibiotic for UTIs: nitrofurantoin. I took it dutifully and my symptoms disappeared. Story over, right?
Wrong. They came roaring back a few weeks later, likely because a small population of nitrofurantoin-resistant bacteria had survived the treatment and had now recolonized my urethra.
Next came Macrobid, a combination treatment of trimethoprim and sulfamethoxazole. I swallowed the last pill just hours before presenting the startup I cofounded, Felix Biotechnology, onstage at the international Falling Walls conference. I explained how our approach, using specific viruses — called phage — that infect and kill bacteria, could overcome the key issues with traditional antibiotics. I even held up the empty bottle during my presentation as an example of why we needed new antibiotic treatments.
But even this combo treatment couldn’t clear the infection and my UTI symptoms continued.
My doctor struggled to find answers and prescribed different antibiotics. But while the previous treatments hadn’t worked due to resistance, the next rounds introduced me to the less-discussed, largely-ignored problem of existing antibiotics: devastating side-effects. I took amoxicillin plus metronidazole to target Gardnerella in case my symptoms were due to bacterial vaginosis. Three doses in, I began vomiting and developed a yeast infection. These side effects aren’t unusual. Traditional antibiotics are the functional equivalent of a nuclear bomb to the microbiome, destroying the disease-causing microbes as well as the good ones that help the body function. The problem is that when the good microbes are cleared out, bad ones often spring up and take over.
Even after enduring 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 UTI symptoms. My doctor prescribed yet another antibiotic: doxycycline. After taking just two doses, my face swelled and my throat tightened in anaphylaxis. It landed me in the emergency room, and I spent most of December 2020 recovering. In January, the specialist prescribed a fifth antibiotic, ciprofloxacin. It worked fantastically: within 24 hours my UTI symptoms disappeared entirely.
The only problem was the rash. It started on the first day as an itchy bump on the back of my leg. By the next day it had turned into an angry, open sore on the back of my calf. Within three days it had spread across my arms and legs, turning my skin into an excruciatingly itchy patchwork of oozing sores that crusted over, only to tear open again when they were touched. I stopped taking cipro and the rash stopped spreading. It healed over the next month, but I still have scars.
After taking — and stopping — the cipro, most of my UTI symptoms disappeared and haven’t come back. But the pain and discomfort when urinating comes and goes, suggesting my body carries 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 aren’t going to rebuild the rich microbiome of millions of species, built over a lifetime and lost in a year.
All this, for a common, non-life-threatening infection. There needs to be a better solution.
A public health problem
In the past year or so, I’ve noticed more people talking about the antibiotic resistance crisis as the possible next pandemic. It’s sometimes referring to it as the “silent pandemic” because it started long before Covid-19 and will continue afterward, but has gone unnoticed despite claiming millions of lives. My fear is that it will take a pandemic-level disruption to our health care system before significant action is taken.
Tens of thousands of people are dying from antibiotic resistant infections right now — the death toll is on par with car crashes — and even more are suffering from the side effects and complications of these drugs. Most of the antibiotics we rely on were developed decades ago and it’s incredible that we’ve 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 we now risk losing even this poor treatment option due to the rise of antibiotic resistance.
It’s particularly frustrating because the market for new antibiotics is so broken that even drugs and approaches with more specificity and better safety profiles can’t turn a profit, all but destroying incentives for companies to invest in this area.
Comparing the R&D landscape for antibiotics to that of nearly every other disease is extremely disheartening. Safer and more-effective medicines are churned out 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 are asked to settle for ancient, failure-prone drugs.
Fortunately, people are starting to listen. Congress is currently considering two pieces of legislation to address the antibiotic development market: the Developing an Innovative Strategy for Antimicrobial Resistant Microorganisms (DISARM) Act (S.1712 and H.R.4100) and the Pioneering Antimicrobial Subscriptions To End Upsurging Resistance (PASTEUR) Act (S.4760 and H.R.8920). Both aim to encourage the development and use of new antimicrobials and reward companies and the health care ecosystem for doing so.
There is on-going debate whether either of these bills will fix the deeply flawed antibiotics 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 don’t just work, but work better.
Natalie Ma is the co-founder and head of business development for San Francisco-based Felix Biotechnology.