Research Discovery May Lead to New UTI Treatments
EXECUTIVE SUMMARY
Recurrent urinary tract infections (UTIs) are extremely common. In a primary care setting, 53% of women above age 55 years and 36% of younger women reported a recurrence within one year.
• Recent research indicates that some UTIs may stem from a persistent reservoir of E. coli residing in the intestine.
• Nitrofurantoin, trimethoprim/sulfamethoxazole (where local resistance is less than 20%), and fosfomycin are appropriate first-line agents for acute uncomplicated cystitis in healthy, nonpregnant, premenopausal women. Fluoroquinolones, such as ciprofloxacin, should be reserved for situations in which other agents are not appropriate.
Recurrent urinary tract infections (UTIs) are extremely common. In a primary care setting, 53% of women above age 55 years and 36% of younger women reported a recurrence within one year.1 Recent research indicates that some infections may stem from a persistent reservoir of E. coli residing in the intestine.2
While UTIs are caused by many species of microorganisms, 80-90% are caused by uropathogenic E. coli, predominantly O, K, and H antigen serotypes.3 Researchers from the University of Queensland and the University of Utah examined the recurrences of UTI in a single patient, who had been treated for infection for 45 years. The patient, who had been treated with almost every type of antibiotic, recalled nine months as her longest symptom-free period.
Researchers performed a genetic analysis to find out if the infection came from a single bacterial reservoir in the body. Scientists isolated E. coli from the patient’s urine during repeat infections and determined its entire DNA sequence. Researchers also collected and sequenced the DNA of E. coli recovered from the patient’s fecal samples. Analysis indicated that the bacteria causing recurring UTIs were identical.
“We now know that bacteria can reside in the intestine for very long periods and cause recurring UTIs, despite antibiotic treatment,” Scott Beatson, PhD, MSc, associate professor at the University of Queensland and a co-author of the current paper, said in a press statement. “Therefore, it’s time we consider using antibiotics that will not just treat the UTI in the bladder, but also eliminate the infection reservoir in the intestine that seeds recurrent infection of the bladder.”
If a patient is seeking treatment for an UTI episode, a fecal sample could determine if the infecting strain also resided in the intestine, using bacterial culture with genome sequencing technology, noted Brian Forde, PhD, first author and University of Queensland scientist.
“If the same strain keeps being identified, we could design tailored treatment to eliminate the bacteria from not just the patient’s urine, but also the intestinal reservoir,” Forde commented in the statement. (The statement is available online at: https://bit.ly/2l2JZxO.)
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About 62.7 million adults age 20 years and older have reported at least one episode of UTI, 81% of whom were women.4 The prevalence of asymptomatic bacteriuria is higher in women than men, occurring in 5-6% of young, sexually active, nonpregnant women, compared with less than 0.1% in young men.5
Most UTI cases are caused by infection traveling from the urethra into the bladder. Bacteria can move up the urethra during urethral massage, sexual intercourse, or mechanical instrumentation, with colonization and infection occurring in the bladder. Staphylococcus saprophyticus often is the cause in lower UTIs and has been isolated in 3% of nonpregnant, sexually active, reproductive-aged women with pyelonephritis.6
Women with acute bacterial cystitis usually present with dysuria, secondary to irritation of the urethral and bladder mucosa. They also may report suprapubic pain or pressure. To determine bacteriuria, a clean-voided midstream urine sample is used. A reading of 100,000 single isolate bacteria per milliliter has been used to define significant bacteriuria, but has a sensitivity of 50%.3 By decreasing the colony count to 1,000-10,000 bacteria per milliliter in symptomatic patients, the sensitivity can be improved without significantly compromising specificity.
According to guidance from the CDC, nitrofurantoin, trimethoprim/sulfamethoxazole (TMP-SMX, where local resistance is less than 20%), and fosfomycin are appropriate first-line agents for acute uncomplicated cystitis in healthy, nonpregnant, premenopausal women. Fluoroquinolones, such as ciprofloxacin, should be reserved for situations in which other agents are not appropriate.7 A three-day antimicrobial regimen is the recommended treatment for uncomplicated acute bacterial cystitis in women.8
REFERENCES
- Aydin A, Ahmed K, Zaman I, et al. Recurrent urinary tract infections in women. Int Urogynecol J 2015; 26:795-804.
- Forde BM, Roberts LW, Phan MD, et al. Population dynamics of an Escherichia coli ST131 lineage during recurrent urinary tract infection. Nat Commun 2019; doi:10.1038/s41467-019-11571-5.
- Fihn SD. Clinical practice. Acute uncomplicated urinary tract infection in women. N Engl J Med 2003;349:259-266.
- Griebling TL. Urinary tract infection in women. In: National Institute of Diabetes and Digestive and Kidney Diseases. Urologic Diseases In America. NIH Publication No. 07-5512. Washington, DC: Government Printing Office; 2007, 587-619.
- Hooton TM, Stamm WE. The vaginal flora and urinary tract infections. In: Mobley HL, Warren JW. Urinary Tract Infections: Molecular Pathogenesis and Clinical Management. Washington, DC: American Society for Microbiology Press; 1996, 67-94.
- Scholes D, Hooton TM, Roberts PL, et al. Risk factors associated with acute pyelonephritis in healthy women. Ann Intern Med 2005; 142:20-27.
- Centers for Disease Control and Prevention. Antibiotic prescribing and use in doctor’s office. Available at: https://bit.ly/2Q5oYNK.
- American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 91: Treatment of urinary tract infections in nonpregnant women. Obstet Gynecol 2008;111:785-794.
Recurrent urinary tract infections (UTIs) are extremely common. In a primary care setting, 53% of women above age 55 years and 36% of younger women reported a recurrence within one year. Recent research indicates that some UTIs may stem from a persistent reservoir of E. coli residing in the intestine.
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