New research on antibiotic resistance in UTIs
Antibiotic resistance is a major threat to human health. I discuss major findings from a recent study from my lab.
This week I’m writing from the west coast, where I am attending and presenting at a scientific conference on antibiotic discovery: Innovative Approaches in Antibacterial Research and Development to Fight the Antibiotic Resistance Crisis.
We’re just two days into the meeting, but there have been some fascinating strategies to discovering new antibiotics shared, from leveraging AI to designing new platforms to find new bacterial targets and to design new molecules to fight the most urgent of these microbial threats. Most antibiotics are molecules that were first found in nature, and there remains a lot of space for exploring and discovering new natural drugs. At the same time, each presentation has underscored the immense threat that drug-resistant microbes pose to human health. Things don’t look good.
In a 2022 paper in The Lancet, researchers revealed that in 2019 there were 1.27 million deaths attributable to antibiotic resistant bacterial infections. We expect the number of annual infections and deaths have risen since 2019, especially considering the increase in antibiotic use throughout the COVID-19 pandemic.
In addition to causing death, there are many difficult to treat infections caused by antibiotic resistant pathogens. In some cases, these infections may not kill you, but can make your life a pain-ridden hell. Take for example patients who get frequent, recurrent urinary tract infections. This is a big problem for post-menopausal women.
My research group, in collaboration with the Emory School of Medicine Department of Gynecology and Obstetrics, undertook a study to investigate one of the potential mechanisms used by microbes to cause recurrent infections. The resistance pathway is a phenomenon known as persistence. Antibiotics work against rapidly growing and dividing cells. When cells transition from regular growth and metabolism to a slower, almost dormant, state (persisters)—they can evade antibiotics and limit the efficacy of antibiotic therapy.
Joseph I, Risener CJ, Falk K, Northington G, Quave CL. Bacterial Persistence in Urinary Tract Infection Among Postmenopausal Population. Urogynecology (Phila). 2024 Mar 1;30(3):205-213. doi: 10.1097/SPV.0000000000001452. Epub 2024 Jan 15. PMID: 38484233; PMCID: PMC10947078.
We collected samples of E. coli from the urine of 40 patients—all postmenopausal women with UTIs. We then studied these bacterial isolates for their capacity to develop a resistant phenotype as persisters and we also evaluated how these responded to different first-line antibiotics.
Here is an excerpt from the article, published this month:
Urinary tract infections are common in women, especially in older-aged women. This can occur because of many factors. Antibiotics are given to treat these urinary tract infections. Unfortunately, antibiotics may not clear these infections completely, and bacteria can remain in the bladder causing repeated infections. Our study examined bacterial persistence, a means by which bacteria survive antibiotic therapy and cause persistent symptoms. In this study, we used antibiotics that are commonly used to treat urinary tract infections in women. Our study involved 30 samples from women with recurrent infections and 10 from acute infections. First, we calculated the lowest antibiotic concentration to inhibit bacterial growth. Next, we introduced the bacteria to these antibiotics to see if bacterial growth occurred despite treatment. We found that all of the acute and recurrent samples had bacterial persistence growth after antibiotic treatment. The acute samples seemed to have more bacterial persistence growth compared with recurrent samples. Fosfomycin was the only antibiotic that led to reduced bacterial persistence growth in both acute and recurrent groups.
Our main questions were:
Do these clinical isolates of bacteria from UTIs form persister cells? And if so,
Do certain antibiotics used in clinical care foster the generation of more resistant persister cells?
In understanding this, we could perhaps better inform clinical care of patients, recommending certain antibiotics over others.
The main findings of this study were that yes, both the recurrent and acute UTI patient urine samples had bacteria present that became persisters. Out of the antibiotics tested (Bactrim, Nitrofurantoin, Ofloxacin, and Fosfomycin), Fosfomycin was the only antibiotic that fostered less persister cell formation in samples from both acute and recurrent UTIs.
Why this Matters
Urinary tract infections occur in approximately 40% of women during their lifetimes. Approximately 20–30% of women will have recurrent infections. Understanding the pathophysiology of urinary tract infection is critical to developing new approaches to therapy. Bacterial persistence is one underlying cause of recurrent infections. First-line antibiotics may have the potential to induce the persister phenotype in women with acute and recurrent infections. Of the three first-line antibiotics tested, fosfomycin was the only antibiotic with reduced bacterial growth in samples from acute and recurrent infections. Bacterial persistence growth seemed to increase with nitrofurantoin treatment. Fosfomycin may be more useful for women with recurrent infections.
The Takeaway
From this study, we learned that bacteria causing UTIs have the capacity to behave as persisters, and that this may lead to more opportunities for treatment resistance. We also learned that in our experimental (test tube) conditions, fosfomycin yielded less bacteria with the persister phenotype than other first-line antibiotics. While further studies are needed, this is an important step in better understanding how patient outcomes may be linked to certain mechanisms of resistance and how antibiotics influence these patterns of resistance.
Yours in health, Dr. Quave
Cassandra L. Quave, Ph.D. is a scientist, author, speaker, podcast host, wife, mother, explorer, and professor at Emory University School of Medicine. She teaches college courses and leads a group of research scientists studying medicinal plants to find new life-saving drugs from nature. She hosts the Foodie Pharmacology podcast and writes the Nature’s Pharmacy newsletter to share the science behind natural medicines. To support her effort, consider a paid or founding subscription, with founding members receiving an autographed 1st edition hardcover copy of her book, The Plant Hunter.
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Very interesting! My mom often had these infections and I wondered why the antibiotics the doctors were prescribing never seemed to solve the problem.
Great article. I wonder how herbs with anti microbial properties would compare.