Updates to Recurrent Uncomplicated Urinary Tract Infections in Women: AUA/CUA/SUFU Guideline.

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You have accessJournal of UrologyJU Forum1 Oct 2022Updates to Recurrent Uncomplicated Urinary Tract Infections in Women: AUA/CUA/SUFU Guideline Brooke R. Bixler and Jennifer T. Anger Brooke R. BixlerBrooke R. Bixler More articles by this author and Jennifer T. AngerJennifer T. Anger More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002888AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Abbreviations and Acronyms AE adverse event EPC Evidence-Based Practice Center NGS next-generation sequencing PAC proanthocyanidin PCR polymerase chain reaction UTI urinary tract infection In 2019 the American Urological Association (AUA) released the evidence-based guideline “Recurrent Uncomplicated Urinary Tract Infections in Women: AUA/CUA/SUFU Guideline.” Information supporting the guideline came from a 2019 systematic evidence review prepared for the AUA by the Pacific Northwest Evidence-Based Practice Center (EPC). The AUA used evidence found in the EPC’s report to derive the 16 guideline statements that make up the 2019 guideline. In 2021 the EPC conducted an updated search to identify potentially relevant studies published since the original 2019 systematic review. A subset of 11 studies were identified as warranting further review to support potential changes to the 2019 guideline. The Panel utilized this updated report to determine whether the data supported, challenged, complemented, or did not add to the current body of evidence for each guideline statement. Following review, all statements were deemed current; however, relevant supporting text was updated based on the findings discussed below. GUIDELINE DISCUSSION, INCREASED WATER INTAKE While water intake is a common discussion point regarding prevention of urinary tract infections (UTIs), there remains insufficient evidence to formally recommend increased fluid intake as an evidence-based preventive measure. The Panel identified a trial of women with recurrent UTIs who reported <1.5 L/day of fluid intake at baseline (140, mean age 36 years). The authors found that increased water intake (>1.5 L/day) was associated with fewer UTI recurrences compared with no additional fluids (mean 1.7 vs 3.2 UTI episodes over 12 months, p <0.001).1 Increased water intake was also associated with a lower likelihood of having at least 3 UTI episodes over 12 months (<10% vs 88%) and greater interval between UTI episodes (143 vs 84.4 days, p <0.001). The increased fluid intake intervention was based on the provision of 3, 500 ml bottles of water to be consumed daily. Daily fluid intake increased from 0.9 L/day to 2.2 L/day in the increased water intake group versus no change in the no additional fluids group. While these data are promising, more research is needed to determine whether or not increased water intake is beneficial to women who regularly drink higher quantities of fluids. ANTIBIOTIC VERSUS METHENAMINE PROPHYLAXIS In the era of growing concern for antimicrobial resistance, nonantibiotic prophylactic alternatives are an important and ongoing area of study. The Panel identified 1 study published in 2021 that showed no difference in efficacy between trimethoprim and methenamine in the prevention of UTIs,2 suggesting better efficacy of methenamine than in prior studies. This study showed no difference in adverse events (AEs) between treatments. As such, the Panel continues to support the use of antibiotic prophylaxis to decrease the risk of future UTIs in women following discussion of the risks, benefits, and alternatives. The Panel notes, however, that the study findings show promise for methenamine as an alternative to prophylactic antibiotics in UTI prevention. NONANTIBIOTIC PROPHYLAXIS The proposed mechanisms of action for the use of cranberry as a prophylactic is thought to be related to proanthocyanidins (PACs) present in cranberries and their ability to prevent the adhesion of bacteria to the urothelium. It must be noted that PACs are found in varying concentrations depending on the formulation used, and many of the cranberry products used in the studies noted below were explicitly formulated for research purposes. The 2019 review included 5 studies of cranberry prophylaxis compared with placebo or no cranberry, and 2 of cranberry versus antibiotic. Three of the 4 new trials of cranberry prophylaxis combined cranberry with different nonantibiotic agents, and a fourth compared high-dose to low-dose cranberry; thus, the new studies could not be combined with those assessed in 2019 or with each other. The study comparing 2 doses of cranberry (PAC) did not show a difference in UTI recurrences or in AEs between doses.3 Similarly, a study of cranberry, propolis (a natural resinous mixture produced by honeybees), and zinc showed no difference compared with placebo.4 A combination of cranberry, D-mannose, and Lactobacillus also showed no difference in outcomes compared with no treatment.5 The fourth study compared high-dose cranberry with Lactobacillus and vitamin A to placebo, and provided low-strength evidence that fewer patients had UTI recurrences with treatment (9.1% vs 33.3%, p=0.0053).6 Rates of AEs were low and did not differ between groups in any new study. These new studies did not impact the current guideline statement because they combined cranberry with 2 other substances. As such, the Panel continues to support the use of cranberry prophylaxis for women with recurrent UTIs. While evidence remains insufficient to recommend other forms of nonantibiotic prophylaxis, research in this space is ongoing. ESTROGEN THERAPY Vaginal estrogen is used in women with genitourinary syndrome of menopause and restores bacterial balance through reducing vaginal pH.7 The Panel identified 1 new study comparing estrogen therapy to placebo in 35 women.7 This study showed that women treated with estrogen had fewer UTI recurrences, similar to the previous findings from the 2019 review. The difference was statistically significant with the addition of the new study (RR 0.58, 95% CI 0.39 to 0.87), but the strength of evidence remained low. The new study did not report AEs. As such, the Panel continues to support the recommendation of vaginal estrogen therapy to reduce the risk of future UTIs in peri- and post-menopausal women. FUTURE RESEARCH IN UTI DETECTION There is growing interest in the study of other methods to allow for the more rapid and accurate identification and treatment of infection. Molecular testing technologies have the potential to provide such information and hold promise for the future by providing a more complete characterization of genitourinary microbes. Polymerase chain reaction (PCR) and next-generation sequencing (NGS) provide a direct assessment of urinary DNA to identify the bacteria present. PCR involves rapid DNA amplification and matching of that DNA to a small set of preselected known organisms.8 PCR testing is very sensitive, provided that the causal organism of interest is present in the PCR test panel. NGS analyzes all microbial DNA within a urine sample and compares it to a database of species, further increasing sensitivity. In studies of patients with and without UTI, PCR has shown good concordance with culture. However, while symptomatic patients were frequently found to have Escherichia coli in their urine by quantitative PCR, so were a significant number of controls.9 Studies comparing NGS to urine culture showed that NGS detects more bacteria and a greater range of organisms within a given urine sample. However, these studies do not examine the positivity rates in culture-negative patients. In a recent study, 44 patients with suspected acute UTI were randomized to treatment based on either culture or NGS.10 Although the NGS group had better improvement in their symptoms, 21 of 22 asymptomatic controls were also positive for bacteria by NGS. To date, more evidence is needed before these technologies become incorporated into the guideline, as there is concern that adoption of this technology in the evaluation of lower urinary tract symptoms may lead to overtreatment with antibiotics. REFERENCES 1. : Effect of increased daily water intake in premenopausal women with recurrent urinary tract infections: a randomized clinical trial. JAMA Intern Med 2018; 178: 1509. Google Scholar 2. : Methenamine hippurate compared with trimethoprim for the prevention of recurrent urinary tract infections: a randomized clinical trial. Int Urogynecol J 2022; 33: 571. Google Scholar 3. : High dose versus low dose standardized cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection in healthy women: a double-blind randomized controlled trial. BMC Urol 2021; 21: 44. Google Scholar 4. : A multicenter, randomized, placebo-controlled study evaluating the efficacy of a combination of propolis and cranberry (Vaccinium macrocarpon) (DUAB®) in preventing low urinary tract infection recurrence in women complaining of recurrent cystitis. Urol Int 2019; 103: 41. Google Scholar 5. : Efficacy of an orally administered combination of Lactobacillus paracasei LC11, cranberry and D-mannose for the prevention of uncomplicated, recurrent urinary tract infections in women. Urologia 2021; 88: 64. Google Scholar 6. : Probiotic and cranberry supplementation for preventing recurrent uncomplicated urinary tract infections in premenopausal women: a controlled pilot study.Expert Rev Anti Infect Ther 2019; 17: 733. Google Scholar 7. : Vaginal estrogen for the prevention of recurrent urinary tract infection in postmenopausal women: a randomized clinical trial. Female Pelvic Med Reconstr Surg 2021; 27: 112. Google Scholar 8. : Next-generation sequencing: a reliable tool for the diagnosis and treatment of complicated and recurrent urinary tract infections. Urology Times; 2022. Available at https://www.urologytimes.com/view/next-generation-sequencing-a-reliable-tool-for-the-diagnosis-and-treatment-of-complicated-and-recurrent-urinary-tract-infections. Google Scholar 9. : Women with symptoms of a urinary tract infection but a negative urine culture: PCR-based quantification of Escherichia coli suggests infection in most cases. Clin Microbiol Infect 2017; 23: 647. Google Scholar 10. : A head-to-head comparative phase II study of standard urine culture and sensitivity versus DNA next-generation sequencing testing for urinary tract infections. Rev Urol 2017; 19: 213. Google Scholar Submitted July 19, 2022; accepted July 19, 2022; published August 1, 2022. Conflict of Interest: The Authors have no conflicts of interest to disclose. Ethics Statement: In lieu of a formal ethics committee, the principles of the Helsinki Declaration were followed. Support: None. © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 208Issue 4October 2022Page: 754-756 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Brooke R. Bixler More articles by this author Jennifer T. Anger More articles by this author Expand All Submitted July 19, 2022; accepted July 19, 2022; published August 1, 2022. Conflict of Interest: The Authors have no conflicts of interest to disclose. Ethics Statement: In lieu of a formal ethics committee, the principles of the Helsinki Declaration were followed. Support: None. Advertisement Advertisement PDF downloadLoading ...