It is estimated that 150 million UTIs occur yearly on a global basis, resulting in more than 6 billion dollars in direct health care expenditures .
Infections are rare in boys except in association with anatomic or functional abnormalities in the first year of life.
Infections are also infrequent among 2- to 13-year-old girls, but some young girls experience multiple repeated episodes of recurrent cystitis or pyelonephritis.
The incidence of UTIs markedly increases among young women during adolescence, with an estimated 7 million acute uncomplicated infections occurring annually in the United States, as determined on the basis of data extrapolated from surveys of physicians.
In a recent prospective study of acute UTIs in young women, the incidence was 0.5–0.7 per year.
Recurrent infections become a problem in 25%–30% of women who experience an initial infection.
Most uncomplicated infections in women do not result in long-term sequelae or renal damage. However, such infections typically cause about 6 days of disability per episode, and thus, in the aggregate, result in substantial morbidity due to their considerable frequency; indeed, they are the most frequent bacterial infections in women.
Estimates of UTI incidence among young men in the same age range are several logs less at 5–8 infections per 10,000.
On the basis of hospital survey data, at least 250,000 cases of pyelonephritis per year occur in the United States.
Among complicated UTIs, those occurring in the hospital as nosocomial infections (primarily urinary catheter–related infections) are the only subgroup for which accurate estimates of frequency are available.
Catheter-associated UTIs account for 40% of all hospital-acquired infections and are thus the most common type of nosocomial infection.
Overall, about 10% of patients with short-term catheterization develop infections. This results in an estimated 1–1.5 million catheter-associated UTIs in the United states per year. Besides accounting for extra hospital costs (∼$400/per episode), these infections may be an important reservoir for selection and transmission of multi-drug–resistant strains and are a frequent source of gram-negative bacteremia in hospitalized patients-
As indicated above, most determinations of UTI incidence and of the costs and morbidity attributable to UTIs have been derived from small, often nonrepresentative databases and, thus, could be described as guesstimates.
Data are particularly absent from developing countries, where it is not known whether UTIs are more frequent or severe than in developed countries.
Additional prospective population-based studies of incidence and cost would be very useful in defining where research should best be directed.
It is not clear, for example, whether UTIs are increasing or decreasing in incidence.
Studies focused on subgroups of patients who are likely to suffer more frequent infection or more severe complications of infection (e.g., diabetics or patients with spinal cord injury) would be very useful.
UTI treatment is the most common reason for antibiotic prescriptions in older adults.
Because of 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 health care system, and contributes to antimicrobial resistance,” said Dr. Kim Orth, Professor of Molecular Biology and Biochemistry at UTSW and senior author of the study, published in the Journal of Molecular Biology.
The investigation demonstrates that several species of bacteria can work their way inside the human bladder’s surface area, called the urothelium, in RUTI patients.
Bacterial diversity, antibiotic resistance, and the adaptive immune response all play important roles in this disease, the study suggests.
“Our findings represent a step in understanding RUTIs in postmenopausal women,” said Dr. Orth, also an Investigator of the prestigious Howard Hughes Medical Institute who holds the Earl A. Forsythe Chair in Biomedical Science and is a W.W. Caruth, Jr. Scholar in Biomedical Research at UTSW. “We will need to use methods other than antibiotics to treat this disease, as now we observe diverse types of bacteria in the bladder wall of these patients.”
Since the advent of antibiotics in the 1950s, patients and physicians have relied on antibiotics for UTI treatment.
“As time went on, however, major antibiotic allergy and resistance issues have emerged, leading to very challenging and complex situations for which few treatment choices are left and one’s life can be on the line,” said Dr. Philippe Zimmern, Professor of Urology and a co-senior author.
“Therefore, this new body of data in women affected by RUTIs exemplifies what a multidisciplinary collaboration can achieve going back and forth between the laboratory and the clinic.”
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 16-36 percent in premenopausal women to 55 percent following menopause.
Factors thought to drive higher UTI rates in postmenopausal women include pelvic organ prolapse, diabetes, lack of estrogen, loss of Lactobacilli in the vaginal flora, and increased colonization of tissues surrounding the urethra by Escherichia coli (E. coli).
The latest findings build on decades of clinical UTI 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 targeted fluorescent markers, a technique that had not been used to look for bacteria in human bladder tissue.
“The bacteria we observed are able to infiltrate deep into the bladder wall tissue, even past the urothelium layer,” said first and co-corresponding author Dr. Nicole De Nisco, an Assistant Professor of Biological Sciences at UT Dallas who initiated this research as a postdoctoral fellow in Dr. Orth’s lab. “We also found that the adaptive immune response is quite active in human RUTIs.”
Accessing human tissue was key, the researchers note, as the field has largely relied 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 age 25 to 40,” said Dr. Zimmern, who holds The Felecia and John Cain Chair in Women’s Health, recently established in his honor.
“This is direct evidence in postmenopausal women affected with RUTIs, a segment of our population that has grown with the aging of baby boomers and longer life expectancy in women.”
Future studies will focus on determining effective techniques to remove these bacteria and chronic inflammation from the bladder, finding new strategies to enhance immune system response, and pinpointing the various bacterial pathogens involved in RUTIs.
More information: Nicole J. De Nisco et al, Direct Detection of Tissue-Resident Bacteria and Chronic Inflammation in the Bladder Wall of Postmenopausal Women with Recurrent Urinary Tract Infection, Journal of Molecular Biology (2019). DOI: 10.1016/j.jmb.2019.04.008
Journal information: Journal of Molecular Biology
Provided by UT Southwestern Medical Center