Abundant urinary amino acids activate glutamine synthetase-encoding glnA by two different mechanisms in Escherichia coli.

Growth of uropathogenic Escherichia coli in the bladder induces transcription of glnA which codes for the ammonia-assimilating glutamine synthetase (GS) despite the normally suppressive high ammonia concentration. We previously showed that the major urinary component, urea, induces transcription from the Crp-dependent glnAp1 promoter, but the urea-induced transcript is not translated. Our purpose here was to determine whether the most abundant urinary amino acids, which are known to inhibit GS activity in vitro, also affect glnA transcription in vivo. We found that the abundant amino acids impaired growth, which glutamine and glutamate reversed; this implies inhibition of GS activity. In strains with deletions of crp and glnG that force transcription from the glnAp2 and glnAp1 promoters, respectively, we examined growth and glnA transcription with a glnA-gfp transcriptional fusion and quantitative reverse transcription PCR with primers that can distinguish transcription from the two promoters. The abundant urinary amino acids stimulated transcription from the glnAp2 promoter in the absence of urea but from the glnAp1 promoter in the presence of urea. However, transcription from glnAp1 did not produce a translatable mRNA or GS as assessed by a glnA-gfp translational fusion, enzymatic assay of GS, and Western blot to detect GS antigen in urea-containing media. We discuss these results within the context of the extremely rapid growth of uropathogenic E. coli in urine, the different factors that control the two glnA promoters and possible mechanisms that either overcome or bypass the urea-imposed block of glutamine synthesis during bacterial growth in urine.IMPORTANCEKnowledge of the regulatory mechanisms for genes expressed at the site of infection provides insight into the virulence of pathogenic bacteria. During urinary tract infections-most often caused by Escherichia coli-growth in urine induces the glnA gene which codes for glutamine synthetase. The most abundant urinary amino acids amplified the effect of urea which resulted in hypertranscription from the glnAp1 promoter and, unexpectedly, an untranslated transcript. E. coli must overcome this block in glutamine synthesis during growth in urine, and the mechanism of glutamine acquisition or synthesis may suggest a possible therapy.

Competitive fitness of asymptomatic bacteriuria E. coli strain 83972 against uropathogens in human urine.

Urinary tract infection (UTI) is one of the most common bacterial infections worldwide. The main causative agent of UTI is uropathogenic Escherichia coli (UPEC). There is an immediate need for novel prophylactic and treatment strategies against UTI because of the increasing incidence of antimicrobial resistance among uropathogens. ABU 83972, an asymptomatic bacteriuria-causing E. coli strain, prevents UTI by suppressing the colonization of UPEC. However, the nature of competition and growth repression of UPEC by ABU 83972 is unclear and is the subject of our investigation. Here, we characterized the growth kinetics of ABU 83972 and uropathogens in human urine and laboratory media. Next, we performed a series of competitive co-culture experiments where ABU 83972 and uropathogens were inoculated at a 1:1 ratio in human urine and in various media, and their relative abundance was determined. In human urine, ABU 83972 outcompeted UPEC and additional uropathogens, reaching up to 90% of the total population after 24 hours of incubation. In contrast, UPEC outcompeted ABU 83972 in LB and M9 minimal media and exhibited superior colonization than ABU 83972 in the mouse urinary bladder. Since engineered living materials (ELMs) can be used to retain an organism of interest in a particular location, we developed ABU 83972-containing ELMs that effectively outcompeted UPEC in human urine. In summary, our work establishes that ABU 83972 outcompetes UPEC in a milieu- and cell-density-dependent manner, highlighting the importance of the metabolites and nutrients found in the human urine as determinants of the competitive fitness of ABU 83972.

Laser excision of urethral mesh erosion: a 10-year experience.

PURPOSE: To review our 10-year experience with laser excision for urethral mesh erosion (UME) of mid-urethral slings (MUS). METHODS: Following Institutional Review Board approval, the charts of female patients with endoscopic laser excision of UME were retrospectively reviewed. Demographics, clinical presentation, surgical history, pre- and post-operative Urinary Distress Inventory-6 scores and quality of life ratings, operative reports, and outcomes were obtained from electronic medical records. UME cure was defined as no residual mesh on office cystourethroscopy 5-6 months after the final laser excision procedure. RESULTS: From 2011 to 2021, 23 patients met study criteria; median age was 56 (range 44-79) years. Twenty (87%) had multiple prior urogynecologic procedures. Median time from MUS placement to presentation with UME-related complaints was 5.3 [interquartile range (IQR) 2.3-7.6] years. The most common presenting symptom was recurrent urinary tract infection (rUTI) (n = 10). Median operating time was 49 (IQR 37-80) minutes. Median duration of follow-up was 24 (IQR 12-84) months. Fourteen (61%) required more than 1 laser excision procedure for UME. Although 5 were asymptomatic (22%), new (n = 5) or persistent (n = 8) urinary incontinence was the most common symptom on follow-up (57%). CONCLUSION: UME presenting symptoms are highly variable, necessitating a high index of suspicion in patients with a history of MUS, especially in the case of rUTI. Endoscopic laser excision is a minimally invasive, brief, safe, outpatient procedure with a high UME cure rate.

Recommendations of the SUFU/AUGS/ICS Female Stress Urinary Incontinence Surgical Publication Working Group: A common standard minimum data set for the literature.

INTRODUCTION AND OBJECTIVES: Relevant, meaningful, and achievable data points are critical in objectively assessing quality, utility, and outcomes in female stress urinary incontinence (SUI) surgery. A minimum data set female SUI surgery studies was proposed by the first American Urological Association guidelines on the surgical management of female SUI in 1997, but recommendation adherence has been suboptimal. The Female Stress Urinary Incontinence Surgical Publication Working Group (WG) was created from members of several prominent organizations to formulate a recommended standard of study structure, description, and minimum outcome data set to be utilized in designing and publishing future SUI studies. The goal of this WG was to create a body of evidence better able to assess the outcomes of female SUI surgery. METHODS: The WG reviewed the minimum data set proposed in the 1997 AUA SUI Guideline document, and other relevant literature. The body of literature was examined in the context of the profound changes in the field over the past 25 years. Through a DELPHI process, a standard study structure and minimum data set were generated. Care was taken to balance the value of several meaningful and relevant data points against the burden of creating an excessively difficult or restrictive standard that would disincentivize widespread adoption and negatively impact manuscript production and acceptance. RESULTS: The WG outlined standardization in four major areas: (1) study design, (2) pretreatment demographics and characterization of the study population, (3) intraoperative events, and (4) posttreatment evaluation, and complications. Forty-two items were evaluated and graded as: STANDARD-must be included; ADDITIONAL-may be included for a specific study and is inclusive of the Standard items; OPTIMAL-may be included for a comprehensive study and is inclusive of the Standard and Additional items; UNNECESSARY/LEGACY-not relevant. CONCLUSIONS: A reasonable, achievable, and clinically meaningful minimum data set has been constructed. A structured framework will allow future surgical interventions for female SUI to be objectively scrutinized and compared in a clinically significant manner. Ultimately, such a data set, if adopted by the academic community, will enhance the quality of the scientific literature, and ultimately improve short and long-term outcomes for female patients undergoing surgery to correct SUI.

Control of glnA (glutamine synthetase) expression by urea in non-pathogenic and uropathogenic Escherichia coli.

IMPORTANCE: The bacteria that cause urinary tract infections often become resistant to antibiotic treatment, and genes expressed during an infection could suggest non-antibiotic targets. During growth in urine, glnA (specifying glutamine synthetase) expression is high, but our results show that urea induces glnA expression independent of the regulation that responds to nitrogen limitation. Although our results suggest that glnA is an unlikely target for therapy because of variation in urinary components between individuals, our analysis of glnA expression in urine-like environments has revealed previously undescribed layers of regulation. In other words, regulatory mechanisms that are discovered in a laboratory environment do not necessarily operate in the same way in nature.

Very Long-term Outcomes After Electrofulguration for Antibiotic-refractory Recurrent Urinary Tract Infections in a Predominantly Menopausal Cohort of Women.

PURPOSE: Antibiotic-refractory recurrent urinary tract infections are challenging to manage. Prior studies have shown that, in selected patients, electrofulguration of cystitis may disrupt potential nidus of recurrent urinary tract infections. We report on long-term outcomes of electrofulguration in women with at least 5 years of follow-up. MATERIALS AND METHODS: Following Institutional Review Board approval, we analyzed a cohort of nonneurogenic women with ≥3 symptomatic recurrent urinary tract infections/y and inflammatory lesions on cystoscopy who underwent electrofulguration, excluding those with alternate identifiable etiology for recurrent urinary tract infections or less than 5-year follow-up. Preoperative characteristics, antibiotic regimens, and annual urinary tract infections were reported. Primary outcome was clinical cure (0-1 urinary tract infection/y), improvement (>1 and <3/y) or failure (≥3/y) at last follow-up. Secondary outcomes included need for antibiotics or repeat electrofulguration. A subanalysis was performed for women with >10-year follow-up. RESULTS: From 2006 to 2012, 96 women met study criteria with median age 64. Median follow-up was 11 years (IQR: 10-13.5); 71 women had >10-year follow-up. Prior to electrofulguration, 74% used daily antibiotic suppression, 5% used postcoital prophylaxis, 14% used self-start therapy, and 7% were not on prophylaxis. At last post-electrofulguration visit, 72% of women were cured, 22% improved, and 6% failed. Antibiotic usage decreased post-electrofulguration (P < .05). Five percent were on continuous antibiotics at last follow-up as compared to 74% on continuous antibiotics pre-electrofulguration (McNemar P < .05). Nineteen percent of women underwent a repeat electrofulguration. CONCLUSIONS: In menopausal women with over 5-year follow-up after electrofulguration for antibiotic-refractory recurrent urinary tract infections, there appears to be durable clinical cure and improvement, with decreased need for long-term antibiotics.

Google searches for stress urinary incontinence treatment options: a worldwide trend analysis in the synthetic mesh controversy era.

PURPOSE: To analyze trends in worldwide public interest in the treatment options for stress urinary incontinence around the latest FDA 2019 ban on vaginal mesh for prolapse. METHODS: We used the web-based tool Google Trends to analyse online searches related to the following terms: 'pelvic floor muscle exercises', 'continence pessary', 'pubovaginal slings', 'Burch colposuspension', 'midurethral slings', 'injectable bulking agents'. Data were expressed as relative search volume on a scale of 0-100. Comparisons of annual relative search volume and average annual percentage change, were analyzed to assess loss or gain of interest. Finally, we assessed the impact of the last FDA alert. RESULTS: The mean annual relative search volume for midurethral slings was 20% in 2006 and significantly decreased until 8% in 2022 (p < 0.01). A regular decrease interest was recorded for autologous surgeries but a regain of interest for pubovaginal slings was registered since 2020 (+ 2.8%; p < 0.01). Conversely, a steep interest was noted for injectable bulking agents (average annual percentage change: + 4.4%; p < 0.01) and conservative therapies (p < 0.01). When trends were compared before and after the FDA 2019 alert, a lower research volume was found for midurethral slings, while a higher research volume was observed all others treatments (all p < 0.05). CONCLUSION: The online public researches about midurethral slings have considerably decreased following warnings on the use of transvaginal mesh. There seems to be a growing interest in conservative measures, bulking agents, and recently pubovaginal slings.

Empiric versus culture-based antibiotic therapy for UTIs in menopausal women.

PURPOSE: To assess the benefits and risks associated with empiric prescription of antibiotic therapy for treatment of a urinary tract infection (UTI). METHODS: Following IRB approval menopausal women presenting with a symptomatic UTI to a single urology clinic were prospectively assigned to one of the two treatment groups based on day of presentation: culture-based treatment (CB) (Monday, Tuesday, Wednesday) or empiric treatment (ET) (Thursday, Friday) and started on nitrofurantoin (NF) pending culture results. Both groups were contacted at 7 and 14 days following treatment. Side effects and answers to a standardized questionnaire (UTISA) were recorded. Success was defined as a total UTISA score < 3. Any NF retreatment, use of another antibiotic therapy, or extension of the original antibiotic course was considered treatment failures. RESULTS: From July 2020 to March 2022, 65 women with 80 UTI events were included in the study, with CB treatment used for 60 UTIs and ET used for 23 UTIs. At 7 days after start of treatment, questionnaire failure rate was 44% (20/45) for the CB group and 16% (3/19) for the ET group (P = 0.076). At 14 days following start of treatment, questionnaire failure rate was 31% (13/42) for the CB group and 17% (3/18) for the ET group (P = 0.3). In the ET group, 11% of cultures were found to be resistant to NF. CONCLUSION: Outcomes for the empiric treatment of uncomplicated UTI with NF at both 7 and 14 days are not significantly different than outcomes with culture-based treatment.

Multimodality Imaging of Anterior Compartment Pelvic Floor Repair.

Pelvic organ prolapse (POP) and stress urinary incontinence (SUI) are two common disorders that affect the anterior compartment of the pelvic floor in women. These can be treated conservatively or surgically. Among patients treated surgically, a substantial number present with pain, recurrent POP or SUI, or other conditions that warrant additional interventions. In many of these cases, imaging is key to identifying and characterizing the type of procedure performed, locating synthetic materials that may have been placed, and characterizing complications. Imaging may be particularly helpful when prior surgical records are not available or a comprehensive physical examination is not possible. US and MRI are the most commonly used modalities for such patients, although radiopaque surgical materials may be visible at voiding cystourethrography and CT. The authors summarize commonly used surgical treatment options for patients with SUI and POP, review imaging techniques for evaluation of such patients, and describe the normal imaging appearance and complications of pelvic floor surgical repair procedures in the anterior compartment of the pelvis. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

d-mannosuria levels measured 1 h after d-mannose intake can select out favorable responders: A pilot study.

BACKGROUND: d-mannose is used as preventive measure against recurrent urinary tract infections (RUTIs). We studied d-mannosuria after a challenge test to identify favorable responders that could be targeted for long-term preventive therapy. MATERIAL AND METHODS: Following institutional review board approval, women attending a specialized tertiary care center urology clinic with a history of RUTIs were invited to participate by providing a urine sample (baseline), followed by the intake of home-dose d-mannose, and a second urine sample 1 h later (post). Urine samples were processed according to a d-mannosuria assay technique reported previously by our group. d-mannose concentrations were normalized to urinary creatinine. RESULTS: From July 2020 to March 2021, 26 patients met study criteria. Thirteen had a lower or unchanged ratio of baseline to post d-mannose, whereas 13 were responders. Among 19 taking 2 g, 12 had a lower or unchanged trend and 7 were responders with >20% increase in the d-mannose/creatinine ratio. Comparison of urinary baseline d-mannose/creatinine ratios was significantly different between the responder (mean = 0.337 ± 0.158) and nonresponder (mean = 0.692 ± 0.444; p = 0.016) groups. Urinary post d-mannose/creatinine ratios did not significantly differ between the two groups (p = 0.46). d-mannose-naïve patients had few responders, and age and urinary creatinine did not affect the findings. CONCLUSION: This preliminary study on d-mannose challenge tests indicates a urine response if urinary d-mannose/creatinine ratio is low, which it was in some women with a history of RUTIs.

Electro-fulguration for extensive inflammatory bladder lesions in post-menopausal women with antibiotic-recalcitrant recurrent urinary tract infections.

INTRODUCTION AND HYPOTHESIS: To evaluate how women with uncomplicated antibiotic-recalcitrant recurrent urinary tract infections (RUTIs) and extensive inflammatory bladder lesions on office cystoscopy responded to electro-fulguration (EF) to eliminate these chronic bladder sites. METHODS: After IRB approval, a retrospective study of non-neurogenic women with RUTIs, inflammatory lesions on cystoscopy, and who underwent EF was performed. Lesions were classified through a simplified staging system based on the extent of bladder wall involvement. Only those with extensive bladder wall involvement (stages 3 and 4) at the time of EF were analyzed in this report. Six months after EF, an office cystoscopy was performed, with endoscopic success defined as no lesions seen. The primary clinical outcome was number of symptomatic UTIs after EF, defined as cure (0/year), improvement (1-2/year), and failure (≥3/year). RESULTS: From 2007 to 2019, a total of 57 women met the study criteria, 30 stage 3 and 27 stage 4. Nineteen (63%) were endoscopically successful in stage 3 and 11 (41%) in stage 4. Mean follow-up was 2.9 years (stage 3) and 3.1 years (stage 4). All had at least a 6-month UTI follow-up after the 6 months of office cystoscopy, with 15 patients cured, 37 improved, and 5 failed (all stage 4). CONCLUSIONS: Although EF only resulted in 63% complete endoscopic resolution, the majority experienced a decrease in the frequency of UTIs, suggesting that EF can be durably effective even in women with very extensive cystitis lesions.

Conserved FimK Truncation Coincides with Increased Expression of Type 3 Fimbriae and Cultured Bladder Epithelial Cell Association in Klebsiella quasipneumoniae.

Klebsiella spp. commonly cause both uncomplicated urinary tract infection (UTI) and recurrent UTI (rUTI). Klebsiella quasipneumoniae, a relatively newly defined species of Klebsiella, has been shown to be metabolically distinct from Klebsiella pneumoniae, but its type 1 and type 3 fimbriae have not been studied. K. pneumoniae uses both type 1 and type 3 fimbriae to attach to host epithelial cells. The type 1 fimbrial operon is well conserved between Escherichia coli and K. pneumoniae apart from fimK, which is unique to Klebsiella spp. FimK contains an N-terminal DNA binding domain and a C-terminal phosphodiesterase (PDE) domain that has been hypothesized to cross-regulate type 3 fimbriae expression via modulation of cellular levels of cyclic di-GMP. Here, we find that a conserved premature stop codon in K. quasipneumoniae fimK results in truncation of the C-terminal PDE domain and that K quasipneumoniae strain KqPF9 cultured bladder epithelial cell association and invasion are dependent on type 3 but not type 1 fimbriae. Further, we show that basal expression of both type 1 and type 3 fimbrial operons as well as cultured bladder epithelial cell association is elevated in KqPF9 relative to uropathogenic K. pneumoniae TOP52. Finally, we show that complementation of KqPF9ΔfimK with the TOP52 fimK allele reduced type 3 fimbrial expression and cultured bladder epithelial cell attachment. Taken together these data suggest that the C-terminal PDE of FimK can modulate type 3 fimbrial expression in K. pneumoniae and its absence in K. quasipneumoniae may lead to a loss of type 3 fimbrial cross-regulation. IMPORTANCE K. quasipneumoniae is often indicated as the cause of opportunistic infections, including urinary tract infection, which affects >50% of women worldwide. However, the virulence factors of K. quasipneumoniae remain uninvestigated. Prior to this work, K. quasipneumoniae and K. pneumoniae had only been distinguished phenotypically by metabolic differences. This work contributes to the understanding of K. quasipneumoniae by evaluating the contribution of type 1 and type 3 fimbriae, which are critical colonization factors encoded by all Klebsiella spp., to K. quasipneumoniae bladder epithelial cell attachment in vitro. We observe clear differences in bladder epithelial cell attachment and regulation of type 3 fimbriae between uropathogenic K. pneumoniae and K. quasipneumoniae that coincide with a structural difference in the fimbrial regulatory gene fimK.

A Deception Study to Avoid Recall Bias Confirms Similar Scores for 3 Validated Questionnaires in the Office or Over the Phone in Women With or Without Urinary Incontinence.

PURPOSE: With increasing telehealth technology, confirming the validity of non-office administration of questionnaires intended for office use only is important. We studied 3 validated questionnaires: the Urinary Distress Inventory 6-Short Form, the International Incontinence 7-Short Form, and a quality of life survey using a deception model. MATERIALS AND METHODS: Following Institutional Review Board approval and power calculations, these 3 questionnaires were prospectively administered in women with and without incontinence by phone and then again in person about 2 weeks later. To avoid recall bias, participants were not informed of the study over the phone. After completing their office visit questionnaire scores, they were told about the study and invited to consent for comparison of their phone and in-person questionnaire scores. Non-English speakers and those with an active urinary tract infection, with impaired mental competency, or on a fluid diet were excluded. RESULTS: From June to September 2021, 86 women, including 40 incontinent (30-85 years old) and 46 control (30-85 years old), with similar demographic parameters met all study criteria. Of the 14 questions studied, only 2, ie, Question 1 on the Urinary Distress Inventory 6-Short Form (P = .033) and Question 7 on the International Incontinence 7-Short Form (P = .036), showed rather minimal but statistically significant differences in scores. For incontinent women, only Question 7 on the International Incontinence 7-Short Form (P = .012) showed a significant score difference. CONCLUSIONS: The 3 questionnaire scores were overall comparable when obtained over the phone or during office visits. Women with incontinence, who may otherwise be lost to follow-up or only reachable by telehealth calls, can benefit from the remote administration of these 3 questionnaires.

Reduced urothelial expression of uroplakin-IIIa in cystitis areas in bladders of postmenopausal women with recurrent urinary tract infections: pilot study.

PURPOSE: To study human bladder biopsies to investigate urothelial response to UTI, expression of uroplakin, and urothelial response after healing from cystoscopy with electrofulguration (CEF) treatment for antibiotic-recalcitrant RUTI. METHODS: Following IRB approval, cold cup bladder biopsies from "no cystitis" and "cystitis" regions were obtained from women with antibiotic-recalcitrant rUTI undergoing CEF under anesthesia. "No cystitis" and "cystitis" biopsies from 14 patients (5 had prior CEF, 9 naïve) were analyzed by immunofluorescence (IF) confocal microscopy using antibodies against uroplakin-IIIa. For an additional 6 patients (2 prior CEF, 4 naïve), only "cystitis" area biopsies were taken and analyzed. Cytokeratin 5 (marker for squamous metaplasia) staining was performed on 14 patients. RESULTS: In healthy tissue, uroplakin-IIIa staining was observed as a contiguous line on the luminal surface of umbrella cells. In "cystitis" areas for 19/20 patients, there was either no uroplakin-IIIa staining observed or spotty (+) staining. The "cystitis" regions of all patients had less intense uroplakin-IIIa staining compared to the matched "no cystitis" area in the same patient. In patients post-CEF but requiring repeat EF for persistent RUTI lesions, healed areas served as control and in 3 of 7 patients no uroplakin-IIIa staining was observed. Squamous metaplasia was observed in 10 patients. CONCLUSION: In bladders of postmenopausal women with antibiotic-recalcitrant RUTI, areas with visible cystitis expressed less uroplakin-IIIa, supporting the model of urothelial exfoliation in response to UTI.

Efficacy of antimicrobial intravesical treatment for uncomplicated recurrent urinary tract infections: a systematic review.

INTRODUCTION AND HYPOTHESIS: Intravesical antimicrobials (IVA) provide a localized modality of treatment for recurrent urinary tract infections (rUTIs). Owing to the sporadic use of these treatments, we conducted a systematic review on the efficacy of IVA in the management of uncomplicated rUTIs. METHODS: A systematic review was conducted for all English language articles from inception to April 2021 utilizing the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards with the following databases: PubMed, OVID Embase, Biomed Central, and Scopus. References were cross-examined for further articles. Risk of bias was assessed in the articles included using the Cochrane and Joanna Briggs Institute tools. RESULTS: The initial search resulting in 476 titles led to 15 full-text articles. Of the 13 in the final review (2 RCTs), 3 used gentamicin and 10 used hyaluronic acid IVA. These included 764 participants, mostly women, with a mean age range of 27-80 (median: 53.1). There was a reduction in UTI frequency in 12 out of 13 studies, with 10 studies showing a statistically significant decrease. Dosages of 80 mg of gentamicin per instillation and both 40 mg and 800 mg of hyaluronic acid per instillation were found to be effective in reducing the frequency of UTIs in most studies. Eleven participants reported gentamicin-resistant infections after IVA treatment. Despite high levels of bias in selected categories, the 13 studies were designated to be of high quality for inclusion. CONCLUSIONS: The IVAs gentamicin and hyaluronic acid with chondroitin sulphate demonstrated efficacy in the management of uncomplicated rUTIs, mostly in women.

Very long-term follow-up of autologous pubovaginal fascia slings in women with stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: The objective was to report on the very long-term outcome of a published series of autologous pubovaginal slings (PVS) in women with stress urinary incontinence (SUI). METHODS: Following institutional review board approval, a cohort of well characterized, non-neurogenic women who underwent an autologous PVS (primary [PVS1] and secondary [PVS2]) for SUI was re-evaluated for their very long-term outcome status. Data collected included demographics, validated questionnaires (Urogenital Distress Inventory - short form [UDI-6], Incontinence Impact Questionnaire - short form 7, quality of life), SUI retreatment/operations, and subjective patient-reported SUI improvement (%) and symptom recurrence. The primary outcome was success defined as UDI-6 question 3 (SUI) ≤ 1 and no SUI retreatment/operation. Patients not seen in clinic for 2 years were contacted via a standardized phone interview. RESULTS: From 83 patients with 7-year intermediate follow-up data, 34 (PVS1 = 18, PVS2 = 16) had very long-term follow-up based on clinic visit (7) or phone interviews (27). Those lost to follow-up (49), including 5 deceased, did not differ in demographics and intermediate outcomes from the followed cohort, but lived further away (>75 miles). At a mean age of 74 years, and with a median follow-up of 14.5 years, 53% met the success criteria (PVS1 = 44%, PVS2 = 63%). Mean postoperative questionnaire scores did not differ significantly between intermediate and very long-term follow-ups, and long-term outcomes between PVS1 and PVS2 remained similar. CONCLUSIONS: A majority of women with long-term follow-up after PVS for primary and secondary SUI remained successful more than 14 years after their surgery. Both groups, PVS1 and PVS2, fared equally well, confirming the durability of PVS as a treatment alternative for SUI.

The Nutrient and Energy Pathway Requirements for Surface Motility of Nonpathogenic and Uropathogenic Escherichia coli.

Uropathogenic E. coli (UPEC) is the causative pathogen for most uncomplicated urinary tract infections. Motility is likely to contribute to these infections, and E. coli possesses flagella-dependent swimming motility, flagella-dependent surface motility (often called swarming), and the recently observed pili-dependent surface motility. Surface motility has not been extensively studied, but for the strains that have been tested nonpathogenic E. coli (NPEC) lab strains use pili, NPEC hypermotile derivatives of these lab strains use flagella, and UPEC strains use flagella. Using a representative of these three types of strains, we showed differences in the nutritional and pathway requirements for surface motility with respect to the glucose concentration, the glycolytic pathway utilized, acetogenesis, and the TCA cycle. In addition, glucose controlled flagella synthesis for the NPEC strain, but not for the hypermotile NPEC variant or the UPEC strain. The requirements for surface motility are likely to reflect major metabolic differences between strains for the pathways and regulation of energy metabolism.IMPORTANCEUrinary tract infections (UTIs) are one of the most common bacterial infections and are an increasing burden on the healthcare system because of recurrence and antibiotic resistance (1, 2). The most common uropathogen is E. coli (3, 4), which is responsible for about 80-90% of community acquired UTIs and 40-50% of nosocomial acquired UTIs (2). Virulence requires both pili and flagella, and either appendage can contribute to surface motility, although surface motility of uropathogenic E. coli has not been examined. We found different appendage, nutrient and pathway requirements for surface motility of a nonpathogenic E. coli lab strain and a uropathogenic E. coli We propose that these differences are the result of differences in the pathways and regulation of energy metabolism.

Very long-term follow-up of the anterior vaginal wall suspension procedure for incontinence and/or prolapse repair.

OBJECTIVE: To report outcomes of the anterior vaginal wall suspension (AVWS) procedure for stress urinary incontinence (SUI) and/or anterior compartment prolapse (POP), with minimum 10-year follow-up. METHODS: Following institutional review board approval, a database of patients with > 10-year follow-up after AVWS for bothersome SUI with early stage anterior compartment prolapse (stage ≤ 2) or symptomatic anterior compartment prolapse (stage > 2) was reviewed. Preoperative evaluation included validated questionnaires [Urogenital Distress Inventory-Short Form (UDI-6), Incontinence Impact Questionnaire-Short Form (IIQ-7), quality of life (QoL)], Pelvic Organ Prolapse Quantification (POP-Q), and voiding cystourethrography. Follow-up data was based on clinic visits or telephone interviews for patients not seen in the past 2 years. Telephone interviews used validated questionnaires and were conducted by a third party not involved in patient care. Failure was defined as reoperation for SUI or POP. The influence of lost to follow-up (LTF) was also analyzed. RESULTS: Between 1996 and 2008, 161 of 328 patients met study criteria, with follow-up from phone interviews (103) or clinic visits (58). The LTF patients were deceased (52), mentally disabled (5), or unreachable by telephone (110). Median follow-up was 13.5 years (IQR 11.5-17). Type of follow-up (clinic vs. phone) and uterine status (concomitant/prior/no hysterectomy) did not impact reoperation rates. Reoperation occurred in 23/161 (14%) and consisted of sacrocolpopexy (8), anterior colporrhaphy (5), injectable agents (8), fascial sling (2). CONCLUSIONS: The AVWS procedure to restore anterior vaginal support to the bladder neck and bladder base to correct SUI/POP can provide satisfactory and durable results.

Adverse effects of chronic nitrofurantoin therapy in women with recurrent urinary tract infections in an outpatient setting.

PURPOSE: To review the frequency of adverse events reported with nitrofurantoin (NF) in perimenopausal and menopausal women on prolonged daily prophylaxis in an outpatient setting. METHODS: Electronic medical records of women aged 50-95 prescribed NF by 2 primary urology providers for at least 3 consecutive months from 2006 to 2018 were retrospectively reviewed. Demographics, reason for the initiation, dose and duration of therapy, explanation of therapy interruptions, occurrence of adverse events, comorbid conditions, and relevant lab and imaging results were recorded. The number of months on prolonged therapy were summed. RESULTS: Of the 221 patients included, 167 (77%) were prescribed 100 mg of NF daily with a mean duration of therapy of 1.5 years. The most common indication for therapy was recurrent urinary tract infection prophylaxis. Breakthrough urinary tract infections developed in 88 (40%) patients on prolonged NF therapy but only 10 were not restarted on NF. Four patients (1.8%) were determined to have pulmonary adverse events and 1 (0.4%) developed elevated liver function tests. CONCLUSION: In peri-menopausal and menopausal women, the risks and benefits of chronic NF therapy should be weighed by the clinician and patient prior to prescribing long term NF. Patients must be educated about the potential NF toxicities and clinically monitored for signs and symptoms of potential adverse events while on chronic NF therapy.

Vesicular Cystitis: A Chronic Cystitis Variant Often Unresponsive to Antibiotics and Electrofulguration.

OBJECTIVE: The aim of the study was to report on the presentation and outcomes of vesicular cystitis (VC), a chronic cystitis exhibiting translucent bladder mucosal vesicles, among women with antibiotic-refractory recurrent urinary tract infections (RUTIs). METHODS: An analysis of our Institutional Review Board-approved series on antibiotic-refractory RUTIs was performed, selecting for documented VC lesions on cystoscopy. All patients had RUTIs defined as ≥3 urinary tract infections/year with positive urine culture. All patients were extensively treated with antibiotics with no resolution of RUTIs and were offered electrofulguration (EF) of VC lesions under anesthesia as a last resort. All patients had a 6-month post-EF office cystoscopy documenting persistence or resolution of the lesions, and a clinical outcome assessment based on RUTI frequency. RESULTS: Of 482 patients, 18 (3.7%) treated during 2011-2017 met the study criteria. VC was most commonly found over the dome/anterior wall (7/18, 38%) and as pancystitis (7/18, 38%). There was often concomitant cystitis cystica of the trigone (8/18, 44%). At post-EF cystoscopy, persistence of VC was noted in 10/18 (56%) patients; 6/18 (33%) underwent repeat EF and an additional 3/18 (17%) were retreated due to new lesions after initial resolution. Two (11%) patients required simple cystectomy and urinary diversion due to RUTIs refractory to all interventions. Within a median follow-up of 2.8 years after EF, clinical cure was observed in 5/18 (28%), improvement in 10/18 (56%), and failure in 3/18 (17%) patients. CONCLUSIONS: Among women with antibiotic-refractory RUTIs, VC is an infrequent and persistent form of cystitis with a predilection for non-trigonal bladder surfaces, whose management is challenging.