Urinary Tract Infections in Postmenopausal Women: Insights from Research

Summary

Urinary tract infections (UTIs) are the most commonly reported infections in adult women and have high recurrence rates, especially in postmenopausal women. Recurrent UTI (RUTI) greatly reduces quality of life, places a significant burden on the healthcare system, and contributes to antimicrobial resistance.

Because treatment of RUTIs with long-term antibiotics is often ineffective or poorly tolerated in elderly women, new therapies must be developed.

The molecular basis of RUTI, especially in postmenopausal women, has been unclear because modeling RUTI in mice is difficult, and human data are limited. Invasion of the urothelium and induction of host inflammation are hypothesized to be key mechanisms by which bacterial pathogens cause RUTI.

To expand our understanding of RUTI in humans , we performed a systematic analysis of urine and bladder biopsy specimens from postmenopausal women undergoing cystoscopy with trigonitis fulguration in the advanced treatment of antibiotic-refractory RUTI.

We provide direct evidence that bacteria reside in the bladder wall of postmenopausal RUTI patients and that diverse bacterial species can be isolated from bladder tissue.

Histopathological scoring revealed significant edema and alterations of urothelial architecture in biopsies from RUTI patients. Lymphocytes, including plasma B cells, were detected in the mesenchyme, urothelium, and follicular aggregates in the majority of patients, indicating that the local adaptive immune response is active during human RUTI.

Comments

A UT Southwestern study suggests why urinary tract infections (UTIs) have such a high recurrence rate in postmenopausal women: Several species of bacteria can invade the walls of the bladder.

Treatment of UTI is the most common reason for antibiotic prescriptions in older adults. Due to the prevalence of UTIs, the societal impact is high and treatment costs billions of dollars annually. 

"Recurrent UTI (RUTI) reduces quality of life, places a significant burden on the healthcare system, and contributes to antimicrobial resistance," said Dr. Kim Orth, professor of molecular biology and biochemistry at UTSW and lead author of the study, published in the Journal of Molecular Biology.

Research shows that several species of bacteria can make their way into the surface of the human bladder, called the urothelium, in patients with RUTI.

Bacterial diversity, antibiotic resistance and adaptive immune response play an important role in this disease, the study suggests.

"Our findings represent a step in understanding RUTIs in postmenopausal women," said Dr. Orth, also an investigator at the prestigious Howard Hughes Medical Institute, who holds the Earl A. Forsythe Chair in Biomedical Sciences and is a WW Caruth, Jr. Academic in Biomedical Research at UTSW. "We will need to use methods other than antibiotics to treat this disease, as we now see various types of bacteria on the bladder wall of these patients."

Since the advent of antibiotics in the 1950s, patients and doctors have relied on antibiotics to treat urinary tract infections.

 "However, as time went on, significant allergy and antibiotic resistance issues emerged, leading to very difficult and complex situations for which few treatment options remain and one’s life may be in danger," said Dr. Philippe Zimmern, Professor of Urology. and a co-senior author. "Therefore, this new data set in women affected by RUTIs exemplifies what a multidisciplinary collaboration between the laboratory and the clinic can achieve."

UTIs are one of the most common types of bacterial infections in women, accounting for nearly 25 percent of all infections. Recurrence can range from 16 to 36 percent in premenopausal women to 55 percent after menopause.

Factors thought to lead to higher rates of UTI in postmenopausal women include pelvic organ prolapse, diabetes, lack of estrogen, loss of Lactobacilli in the vaginal flora, and increased colonization of the tissues surrounding the urethra by Escherichia coli ( E.coli).

The latest findings build on decades of IU clinical discoveries by Dr. Zimmern, who suggested the collaboration to Dr. Orth, along with other UT System colleagues.

The UTSW team, which included researchers from Molecular Biology, Pathology, Urology and Biochemistry, examined bacteria in bladder biopsies from 14 RUTI patients using specific fluorescent markers, a technique that had not been used to look for bacteria in the tissue. of the human bladder.

"The bacteria we observed are able to infiltrate deep into the tissue of the bladder wall, even beyond the urothelium layer," said first and co-first author Dr. Nicole De Nisco, associate professor of Biological Sciences at the University of Dallas who began this research as a postdoctoral fellow in Dr. Orth’s laboratory. "We also found that the adaptive immune response is quite active in human RUTIs."

Access to human tissues was key, the researchers note, as the field has relied heavily on mouse models that are limited to lifespans of 1.3 to 3 years, depending on the breed.

"Most of the work in the literature has dealt with women between the ages of 25 and 40," said Dr. Zimmern, who holds the Felecia and John Cain Chair in Women’s Health, recently established in her honor.

"This is direct evidence in postmenopausal women affected with RUTI, a segment of our population that has grown with the aging of baby boomers and increased life expectancy in women."

Future studies will focus on determining effective techniques to eliminate these bacteria and chronic bladder inflammation, find new strategies to improve the immune system response, and pinpoint the various bacterial pathogens involved in SUIs.