We performed a systematic review and meta-analysis to determine whether D-mannose reduces urinary tract infection recurrence (ie, cumulative incidence) in adult women with recurrent urinary tract infection compared with other prevention agents. Secondary outcomes included side effects and compliance with D-mannose use.

Comprehensive, nonoperative management of PFD including pelvic floor muscle training, biofeedback, electrogalvanic stimulation, constipation management, behavioral modification, incontinence devices, and pharmacotherapy including vaginal estrogen is effective in the treatment of women with PFD.

ObjectiveThe aim of the study was to inform feasibility parameters (eligibility, enrollment, and retention) for a recurrent urinary tract infection (rUTI) prevention randomized controlled trial (RCT).MethodsWe assessed feasibility parameters of an RCT of postmenopausal women with uncomplicated rUTIs using vaginal estrogen. Participants were randomized to either d-mannose or a control arm. All participants were required to be using vaginal estrogen and to have a negative urine culture before 90-day trial participation. An RCT exit survey and separate survey for UTI patients (N = 196) were added to inform feasibility parameters and patient preferences for rUTI prevention and study participation after slower enrollment than anticipated.ResultsAt the time of interim and subsequent futility analyses, 545 patients had been evaluated for frequent/recurrent UTIs from March 1, 2018, to January 18, 2020. Of these, 213 (39.1%) had culture-proven rUTIs and 71 (33.3% of those with culture-proven rUTIs) were eligible for the RCT. Reasons for ineligibility included complicated UTIs, premenopausal/perimenopausal status, or existing UTI prevention regimen. Of the 71 eligible participants, 57 (80.3%) enrolled, and 44 began their planned 90-day study period (77.2%; 80.0% after excluding 2 participants awaiting negative urine cultures at the time of analysis). The study was halted before conclusion. Study retention (76.0%–83.7%) was slightly lower than expected. Urinary tract infection survey patients demonstrated significant interest in rUTI research participation.ConclusionsWe learned several important lessons that can benefit future research. Many patients with frequent/recurrent UTIs are interested in research, but rigorous eligibility criteria and referral urine culture documentation made recruitment challenging.

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(Abstracted from Urogynecology (Phila) 2023;29:367–377Up to 25% of women experience recurring urinary tract infections, which are typically managed through long-term antibiotic prophylaxis intended for common urogenital pathogens. Unfortunately, prolonged use of antibiotics can lead to several adverse effects such as allergic reactions, sequelae from microbiome alterations, drug interactions/toxicities, and antibiotic resistance. One commonly prescribed prophylactic therapy, vaginal estrogen therapy (VET), is used as a first-line nonantibiotic therapy for rUTIs.

Purpose:We identify correlates and clinical outcomes of cystitis cystica, a poorly understood chronic inflammatory bladder change, in women with recurrent urinary tract infections.Materials and Methods:A retrospective, observational cohort of women with recurrent urinary tract infections who underwent cystoscopy (n=138) from 2015 to 2018 were identified using electronic medical records. Cystitis cystica status was abstracted from cystoscopy reports and correlations were identified by logistic regression. Urinary tract infection–free survival time associated with cystitis cystica was evaluated by Cox proportional hazards regression. Exact logistic regression was used to identify factors associated with changes to cystitis cystica lesions on repeat cystoscopy. Biopsies of cystitis cystica lesions were examined by routine histology and immunofluorescence.Results:Fifty-three patients (38%) had cystitis cystica on cystoscopy. Cystitis cystica was associated with postmenopausal status (OR: 5.53, 95% CI: 1.39-37.21), pelvic floor myofascial pain (6.82, 1.78-45.04), having ≥4 urinary tract infections in the past year (2.28, 1.04-5.09), and a shorter time to next urinary tract infection (HR: 1.54, 95% CI: 1.01-2.35). Forty-two patients (82%) demonstrated improvement or resolution of lesions. Ten/11 (91%) biopsied cystitis cystica lesions were tertiary lymphoid tissue with germinal centers and resembled follicular cystitis.Conclusions:Cystitis cystica lesions were associated with postmenopausal status, pelvic floor myofascial pain, and number of urinary tract infections in the prior year and predicted worse recurrent urinary tract infection outcomes. Cystitis cystica lesions are tertiary lymphoid tissue/follicular cystitis that may improve or resolve over time with treatment. Identifying cystitis cystica in recurrent urinary tract infection patients may be useful in informing future urinary tract infection risk and tailoring appropriate treatment strategies.

ImportanceFurther research is needed to determine whether d-mannose plus vaginal estrogen therapy (VET) is beneficial over VET alone for recurrent urinary tract infection (rUTI) prevention.ObjectiveThe aim of this study was to evaluate d-mannose efficacy for rUTI prevention in postmenopausal women using VET.Study DesignWe conducted a randomized controlled trial comparing d-mannose (2 g/d) with control. Participants were required to have a history of uncomplicated rUTIs and to remain on VET throughout the trial. They were followed up 90 days for incident UTIs. Cumulative UTI incidences were calculated by the Kaplan-Meier method and compared by Cox proportional hazards regression. For the planned interim analysis, P < 0.001 was considered statistically significant. Futility analysis was performed by generating post hoc conditional power for multiple scenarios.ResultsWe evaluated 545 patients for frequent/recurrent UTIs from March 1, 2018, to January 18, 2020. Of these women, 213 had culture-proven rUTIs, 71 were eligible, 57 enrolled, 44 began their planned 90-day study period, and 32 completed the study. At interim analysis, the overall cumulative UTI incidence was 46.6%; 41.1% in the treatment arm (median time to first UTI, 24 days) and 50.4% in the control arm (median, 21 days); hazard ratio, 0.76; 99.9% confidence interval, 0.15–3.97. d-Mannose was well tolerated with high participant adherence. Futility analysis suggested the study lacked power to detect the planned (25%) or observed (9%) difference as statistically significant; the study was halted before conclusion.Conclusionsd-Mannose is a well-tolerated nutraceutical, but further research is needed to determine whether d-mannose in combination with VET has a significant, beneficial effect beyond VET alone in postmenopausal women with rUTIs.