The antibiotic stigma associated with recurrent UTIs

Recurrent urinary tract infections (UTIs) place a large burden on women as they struggle to find the right remedies for this problem. According to guidelines, there is only 1 temporary cure for this condition and that is antibiotics. As more antibiotics are taken by this susceptible population, however, the bacteria can adapt and make recurrent UTI treatment in the future much more difficult.

J. Curtis Nickel, MD, FRCSC, discusses the antibiotic stigma associated with recurrent UTIs in a recent interview. Along with dissecting the issue, he gives advice to practicing urologists about prescribing treatment and highlights research that could potentially transform recurrent UTI treatment for good. Nickel is a professor of urology at Queen’s University, and a research chair in urologic pain and inflammation at Kingston Health Sciences Centre, Kingston, Ontario, Canada.

What is the scope of the problems surrounding recurrent UTIs?

We have all come to understand that recurrent urinary tract infection in women is a major health care problem. Depending on what literature you read, between 40% and 60% of women suffer from urinary tract infection sometime in their lifetime. Many of these women have recurrences, and these recurrences can occur within 6 months in about 20% of patients who have an incidental urinary tract infection. One in 5 women overall suffer recurrent urinary tract infections that is defined as greater or equal to 3 UTIs per year. However, many of these women suffer much more, with the average being 6 UTIs per year in this population of women with recurrent urinary tract infection. To summarize, in the course of any year, 11% of women will suffer a urinary tract infection while 3 out of 100 will suffer from recurrent urinary tract infections. So, this really is a major health care issue.

How is the personal burden surrounding recurrent UTIs a problem for patients?

We usually think of recurrent urinary tract infections as uncomplicated, simple infections that will resolve with our standard antibiotic therapy. However, in reality, recurrent urinary tract infections can cause severe debilitating health consequences. Patients suffer recurrent bladder and urinary pain and bothersome urinary symptoms each time they get an infection. These women suffer from disability, and by disability, I mean problems doing life activities, including employment. Studies have shown that women with recurrent urinary tract infections have significantly worse mental health compared to a normal population. And it's even more significant in some aspects of physical health, but particularly physical sexual health. We also note that as part of this, patients have trouble with their overall social well-being. This translates into a very poor quality of life for women suffering from recurrent urinary tract infections.

And then we look at the impact of the treatment they have to endure. There are multiple short- and long-term side effects from antibiotics including serious, irreversible side effects that many of these women end up having. They can develop intolerances or allergies to the standard antibiotics prescribed, and this can make it more difficult to treat subsequent infections. Many of these women, because of the long-term accumulation of antibiotics from either multiple episodic or prophylactic dosing that can be prescribed for 3 months or as long as 12 months, develop a personal reservoir of resistant uropathogens in their gut that can make treatment of subsequent urinary tract infections very difficult, sometimes requiring parental or intravenous antibiotics for simple recurrent uncomplicated UTIs. And then again, there's the problem—rare, but it does occur—that patients can transition or develop complicated urinary tract infections, serious episodes of pyelonephritis and even urosepsis. Some of these consequences are associated with the threat of hospitalization, and in rare cases, even death.

And finally, frequent use of episodic antibiotics or longterm prophylactic antibiotics to treat or prevent urinary tract infection, change the patient's personal microbiome to an unhealthy state. Our gut microbiome is important to keep us healthy. It impacts our reaction to stress, anxiety, sleep, and well-being, and changing that to a dysbiotic or somewhat polluted gut microbiome with less diversity caused by antibiotics, can be a very unhealthy state for these women. It also impacts the microbiome of the vagina, leading to increased yeast overgrowth and yeast vaginitis. In addition, it can impact the microbiome of the bladder, leading to less diversity, sensitization, and even chronic pain states between episodes of recurrent urinary tract infections. So, as you can see, there is a huge personal burden associated with a diagnosis of recurrent urinary tract infections, despite the fact that it appears we have effective therapy with the use of antibiotics.

Are there any stigmas related to this condition?

Yes, there is, and it's becoming more obvious with our knowledge about the increasing importance of overall anti-microbial resistance that is evolving in this patient population and in society as a whole. Antibiotic treatment and prophylaxisis the only guideline-recommended therapy in North America. It does work, but it comes with all sorts of problems. We talked about the mild, moderate, severe, and even irreversible adverse events associated with antibiotic use. But overall, the 1 major issue that we see from a population perspective is the fact that it promotes anti-microbial resistance. So, the stigma is that the massive use of antibiotics in this population is helping to drive the overall cost, the difficulty in treating infection, and the transition to serious UTIs and even mortality, in not only these patients but other patients because of this massive use of antibiotics in this population. That's really the only stigma and it's not the fault of the patients with recurrent urinary tract infection, and most of us in the medical profession realize that this stigma is more the result of our only treatment we have for this condition.

What can urologists do about this stigma?

We can do something about it for our patient population and for this stigma of promoting antibiotic resistance in our community. The most important thing is antibiotic stewardship. We have to be very careful of what antibiotics we prescribe for UTIs, try and stick to the first-line anti-microbial therapy that's recommended by guidelines, try and keep the course of anti-microbial therapy as short as possible, but long enough to treat and eradicate the bacteria, and be careful how we use prophylaxis. Perhaps a stewardship program of post-coital antibiotics will achieve the same results in sexually active young women compared to long-term, 3-to-12-month prophylaxis. Alternate day prophylactic therapy works in many patients. Keep the dose and duration as low as possible with planned drug holidays. And then we can recommend conservative measures. We've always done that, including post-bowel hygiene, the non-use of douches, baths versus showers, and the type of clothing patients wear, but none of these really benefit the patient. They actually can cause self-guilt and personal anxiety. The only conservative measure that's really proven is to increase water intake. If patients increase their water intake to 2 liters per day, yes, they'll void a little bit more often, but that dilution of the lower urinary tract keeps the uropathogenic bacteria at bay and we do reduce urinary tract infections.

For postmenopausal patients, evidence-based use of intravaginal estrogen reduces UTIs in this population. It's not the panacea and it doesn't work for everybody, but it certainly reduces the recurrent UTIs in the susceptible patients. We can use various supplements, like cranberry extract, but it's important that we use those with a described dose of proanthocyanidins (PACS). We can use D-mannose, particularly in patients with E. coli recurrent urinary tract infections. Probiotics might help to improve or regenerate the microbiome of the gut and the vagina. And prebiotics, trying to feed the good bacteria in our microbiome can be accomplished by a good, healthy diet. A number of dietary improvements can be made in many of our patients that will help their microbiome fight infection.

Finally, I believe that science is going to help. I recently presented, in the late-breaking abstract session at the 2021 American Urological Association Annual Meeting, the exciting potential of a new, very safe sublingual vaccine, MV140, which significantly reduces recurrent urinary tract infections in this population of women; in fact, preventing it in almost 60% of women who once had a median of 6 UTIs going to a median of 0 UTIs in a 9-month efficacy period. This particular vaccine is being used in special access or compassionate drug programs in Europe, Australia, New Zealand, and the UK. And to date, over 40,000 patients have received this vaccine and it has shown safety and appears, in observational studies and this most recent pivotal trial, to be efficacious. So, I do believe that there's something that physicians will be able to offer beyond these conservative measures and antibiotic stewardship in the future. I think our goal is to reduce antibiotic use in this population, while reducing the issue of recurrent urinary tract infections in our female population.

Is there anything else you feel our audience should know about this topic?

I think it's important to address the issue of the burden that these patients are carrying. We have to address the fact that overuse of antibiotics in this population is a major healthcare problem, and see what we can do through antibiotic stewardship. We have to explore all the conservative measures we can in this population to reduce overall antibiotic usage. The perceived stigma that this population is promoting antibiotic resistance is not the patient’s fault. It's our responsibility as physicians and urologists to find the answers for our patients. And I do think the evolving science, as I mentioned, is going to help us help our patients. Any burden or stigma associated with this condition will gradually improve as we get better at addressing the underlying issue by reducing the risk of developing recurrent UTIs.