Bacterial species cultured after electrofulguration in women with a history of antibiotic-recalcitrant urinary tract infections frequently compare with pre-fulguration findings: a pilot study.

Electrofulguration (EF) of areas of chronic cystitis in women with antibiotic-recalcitrant recurrent urinary tract infections (RUTIs) can result in improvement of their urinary tract infections (UTIs). We compared urine culture (UC) findings in patients before and after EF, as well as how they vary with cystitis stage at the time of EF, to evaluate for persistent species. After obtaining institutional review board approval, we retrospectively reviewed a prospectively maintained database of EF patients for those with positive UC findings in the 3-6 months preceding EF. Patient pre-EF UC was then compared with first positive UC after EF prompted by a new symptomatic UTI episode, with the hypothesis that the same species will be identified before and after EF. Exclusion criteria included UC from outside institution, neurogenic bladder, and need for catheterization. Ninety-nine women with pre- or post-EF UC-recorded organisms met the study criteria. The median age was 65 years (interquartile range 64-74), with a median time to first positive culture following fulguration of 9.7 months. For 26 patients with positive cultures both pre- and post-EF, the same organism was present in both cultures in 73% of the patients, with predominantly Escherichia coli. EF was effective at reducing the rate of UTIs in this population. For women undergoing EF for antibiotic-recalcitrant RUTIs and associated chronic cystitis lesions, 73% of those with a UC obtained at the time of a first symptomatic recurrent UTI episode post-EF expressed the same organism as before EF. Further study is needed to better understand the evolution of the microbiome post-EF.IMPORTANCEAmong women who experience a recurrent urinary tract infection after a fulguration procedure on areas of chronic cystitis in their bladder, there are no data available on whether the bacterial species found in urine cultures are the same or different from those present before fulguration. By removing the inflamed surface layer of cystitis during fulguration, it is possible that the procedure unmasks deep-seated bacteria. The bacterial kingdom in the bladder wall of these chronically infected women may be different from what is expressed sporadically in urine cultures. Confirming prior studies, we found that fulguration in women with antibiotic-recalcitrant recurrent urinary tract infections and cystitis lesions was effective at reducing the rate of urinary tract infections. At the time of a first symptomatic recurrent UTI episode post-fulguration, 73% expressed the same organism in urine culture as before fulguration. Further study is needed to better understand the evolution of the microbiome post-EF. This article evaluates persistent infections after electrofulguration of areas with chronic cystitis in post-menopausal women with antibiotic-recalcitrant recurrent urinary tract infections. Pre-fulguration urine cultures were compared with the first positive urine culture prompted by a new symptomatic UTI episode after electrofulguration, with the hypothesis that the same species will be identified before and after the fulguration procedure. Electrofulguration was effective at reducing the rate of UTIs in this population. However, 73% of those with a urine culture obtained at the time of a first symptomatic recurrent UTI episode post-electrofulguration expressed the same organism (predominantly Escherichia coli) as before the fulguration procedure. Further study is needed to better understand the evolution of the microbiome after electrofulguration.

Systematic Review of the Global Use of Validated Questionnaires in the Management of Stress Urinary Incontinence in Women.

INTRODUCTION: Our goal was to systematically review the most commonly used validated questionnaires in recent global literature on stress urinary incontinence (SUI) treatment. METHODS: PubMed, Embase, and Ovid databases were queried for manuscripts containing "female stress urinary incontinence" AND "diagnosis" AND "treatment" AND "questionnaire." Two independent reviewers screened studies for randomized controlled trials, prospective, and retrospective studies between 2018 and 2023. Exclusion criteria included male participants, non-SUI incontinence, and articles not originally written in English. The review was registered in PROSPERO [465721] and conformed to PRISMA guidelines. RESULTS: In 117 manuscripts meeting study criteria, the median of the mean ages was 52 years, with a median of 164 participants per study. Most studies originated in Europe (59/117). The International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form was the most frequently used (52%), followed by the Patient Global Impression of Improvement (31%), the Urinary Distress Inventory 6 Short Form (25%), the Incontinence Quality of Life (20%), and the Incontinence Impact Questionnaire Short Form (19%). These leading questionnaires were short, translated into several languages, and globally addressed important SUI-related domains, including the presence and severity of SUI, additional lower urinary tract symptoms, and the impact of SUI on quality of life, as well as changes perceived after treatment. CONCLUSIONS: This systematic review of the validated questionnaires used in contemporary SUI management literature could help guide recommendations for incorporating these favored instruments into future SUI treatment outcome documents.

Systematic Review of the Global Literature on Uncomplicated Recurrent Urinary Tract Infections in Women: Underscoring Major Heterogeneity.

OBJECTIVE: To examine the global literature database on uncomplicated recurrent urinary tract infections (rUTI), this systematic review assesses the availability of rUTI data based on geographic region and elucidates the current state of research and gaps in knowledge. METHODS: The databases PubMed, Embase, WHO Global Index Medicus, and SciELO were searched for keywords related to rUTI between 2000 and 2023. Three independent reviewers screened studies restricted to female participants age ≥18 years with uncomplicated rUTIs. Studies were excluded if they did not provide a definition for rUTI or did not cite or report an estimate for rUTI prevalence. The review was registered in PROSPERO and conformed to PRISMA guidelines. RESULTS: The search yielded 2947 studies of which 124 were ultimately included. Convenience samples were used for 91% of studies and sample sizes were 30% n <50, 29% n = 50-99, 22% n = 100-199, 36% n ≥200. Most studies were conducted in Europe (41%) or North America (39%), were prospective (52%), at tertiary centers (49%) and included all ages ≥18 (60%). The most common definition for rUTI was 2 UTI/6 m or 3 UTI/1y (62%). Regardless of study location, most studies cited prevalence estimates for rUTI derived from U.S.-based populations. CONCLUSION: This study represents the first formal investigation of the global literature base on uncomplicated rUTI. Studies on rUTIs are globally of small scale and definitions used for rUTI are heterogeneous. More studies are needed to ascertain the true prevalence of rUTI outside of North America and Europe.

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.

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) post-treatment 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.

Genome sequencing of correlated pathogenic Escherichia coli and Enterococcus associated with recurrent urinary tract infections.

Reported here are the sequences for 11 Escherichia coli and four Enterococcus strains isolated from post-menopausal women with a recurrent urinary tract infection. Each of the Enterococcus strains were isolated along with an E. coli strain. This provides a resource of high-quality complete genomes from polymicrobial infections.

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.

Inflammatory markers for improved recurrent UTI diagnosis in postmenopausal women.

Recurrent urinary tract infection (rUTI) severely impacts postmenopausal women. The lack of rapid and accurate diagnostic tools is a major obstacle in rUTI management as current gold standard methods have >24-h diagnostic windows. Work in animal models and limited human cohorts have identified robust inflammatory responses activated during UTI. Consequently, urinary inflammatory cytokines secreted during UTI may function as diagnostic biomarkers. This study aimed to identify urinary cytokines that could accurately diagnose UTI in a controlled cohort of postmenopausal women. Women passing study exclusion criteria were classified into no UTI and active rUTI groups, and urinary cytokine levels were measured by immunoassay. Pro-inflammatory cytokines IL-8, IL-18, IL-1ß, and monocyte chemoattractant protein-1 were significantly elevated in the active rUTI group, and anti-inflammatory cytokines IL-13 and IL-4 were elevated in women without UTI. We evaluated cytokine diagnostic performance and found that an IL-8, prostaglandin E2, and IL-13 multivariable model had the lowest misclassification rate and highest sensitivity. Our data identify urinary IL-8, prostaglandin E2, and IL-13 as candidate biomarkers that may be useful in the development of immunoassay-based UTI diagnostics.

Robotic simple cystectomy as a last resort for antibiotic-recalcitrant recurrent urinary tract infections in women.

OBJECTIVE: To report a series of women with antibiotic-recalcitrant recurrent urinary tract infections (rUTI) managed with robotic simple cystectomy and ileal conduit urinary diversion. METHODS: Following Institutional Review Board approval, all female patients who underwent robotic cystectomy for rUTI between 2011 and 2021 were identified from a prospectively-maintained internal database at a tertiary care center. Exclusion criteria included interstitial cystitis, neurogenic bladder, urinary tract neoplasm, or congenital abnormality. Electronic medical records were reviewed by an independent researcher. Patients were also administered the Quality of Life Questionnaire-C30. RESULTS: Twenty-four patients met inclusion criteria. Median age was 75 years (range 53-87). Median rUTI duration was 6 (interquartile range [IQR] 2-10) years. Median urinary tract infections count in the 12-month preceding cystectomy was 5 (IQR 3-9). Infections with multidrug resistant organisms were found in 21 patients (88%). The 30-day postoperative complication rate was 79% (19/24), of which 11% were Clavien-Dindo grade ≥III. The main late complication was parastomal hernia, with 17% requiring repair or revision. At a median of 36 months (range 12-61) post-operatively, the median Quality of Life Questionnaire-C30 global health status score was 50 (range 33-83). CONCLUSION: Cystectomy is a last-resort management option for women with severely symptomatic end-stage bladders in the setting of antibiotic-recalcitrant rUTI. Patients should be counseled thoroughly regarding possible acute and long-term postoperative complications. Select patients, managed in high-volume referral centers, can benefit from robotic simple cystectomy with ileal conduit urinary diversion.

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.

Identifying Patient and Surgical Criteria for Same-Day Discharge After Robotic-Assisted Sacrocolpopexy.

Introduction: To review the postrobotic-assisted sacrocolpopexy (RASC) course of women admitted for 23 hours post-RASC and identify events requiring intensive medical care or potentially leading to deleterious outcome or urgent readmission if that patient had same-day discharge (SDD) instead of observed overnight. Methods: Patients undergoing RASC from January to December 2020 at one institution were identified and relevant data were obtained via retrospective chart review. Patient exclusions: RASC start time after 12:00 PM, concurrent posterior colporrhaphy, rectopexy, or hysterectomy, or conversion to open. Results: Sixty-nine patients (median age 71 years old) met study criteria with majority American Society of Anesthesiologists class 2 (n = 46, 67%) or 3 (n = 22, 32%). Patient characteristics included prior abdominal surgeries (n = 58, 84%), prior hysterectomy/prolapse repair (n = 25, 37%), known allergy to pain medication (n = 25, 36%), and administration of a postoperative antiemetic (n = 37, 54%) or intra-/postoperative keterolac (n = 36, 52%). Median surgery length was 269 minutes. Postoperative events that may have resulted in urgent readmissions if they had SDD were observed in 6% of patients. In the 1st week post-RASC, there were no readmissions. Conclusions: In this limited quality assurance study, patients undergoing RASC experienced no major complications requiring intensive care. Postoperative events were almost entirely nausea and pain, with no readmissions within the 1st week.

VesiX cetylpyridinium chloride is rapidly bactericidal and reduces uropathogenic Escherichia coli bladder epithelial cell invasion in vitro.

Management of urinary tract infection (UTI) in postmenopausal women can be challenging. The recent rise in resistance to most of the available oral antibiotic options together with high recurrence rate in postmenopausal women has further complicated treatment of UTI. As such, intravesical instillations of antibiotics like gentamicin are being investigated as an alternative to oral antibiotic therapies. This study evaluates the efficacy of the candidate intravesical therapeutic VesiX, a solution containing the cationic detergent Cetylpyridinium chloride, against a broad range of uropathogenic bacterial species clinically isolated from postmenopausal women with recurrent UTI (rUTI). We also evaluate the cytotoxicity of VesiX against cultured bladder epithelial cells and find that low concentrations of 0.0063% and 0.0125% provide significant bactericidal effect toward diverse bacterial species including uropathogenic Escherichia coli (UPEC), Klebsiella pneumoniae, Enterococcus faecalis, Pseudomonas aeruginosa, and Proteus mirabilis while minimizing cytotoxic effects against cultured 5637 bladder epithelial cells. Lastly, to begin to evaluate the potential utility of using VesiX in combination therapy with existing intravesical therapies for rUTI, we investigate the combined effects of VesiX and the intravesical antibiotic gentamicin. We find that VesiX and gentamicin are not antagonistic and are able to reduce levels of intracellular UPEC in cultured bladder epithelial cells. IMPORTANCE: When urinary tract infections (UTIs), which affect over 50% of women, become resistant to available antibiotic therapies dangerous complications like kidney infection and lethal sepsis can occur. New therapeutic paradigms are needed to expand our arsenal against these difficult to manage infections. Our study investigates VesiX, a Cetylpyridinium chloride (CPC)-based therapeutic, as a candidate broad-spectrum antimicrobial agent for use in bladder instillation therapy for antibiotic-resistant UTI. CPC is a cationic surfactant that is FDA-approved for use in mouthwashes and is used as a food additive but has not been extensively evaluated as a UTI therapeutic. Our study is the first to investigate its rapid bactericidal kinetics against diverse uropathogenic bacterial species isolated from postmenopausal women with recurrent UTI and host cytotoxicity. We also report that together with the FDA-approved bladder-instillation agent gentamicin, VesiX was able to significantly reduce intracellular populations of uropathogenic bacteria in cultured bladder epithelial cells.

Long-term Outcomes With Macroplastique in Women With Stress Urinary Incontinence Secondary to Intrinsic Sphincter Deficiency.

OBJECTIVE: To evaluate the long-term outcomes of polydimethylsiloxane (Macroplastique (MPQ)) in women with stress urinary incontinence (SUI) secondary to intrinsic sphincter deficiency (ISD) using validated questionnaires. METHODS: Following IRB approval, charts of non-neurogenic women with SUI secondary to ISD who underwent MPQ injection were reviewed from a prospectively maintained database. ISD was defined as positive stress test with a well-supported urethra and low Valsalva leak point pressure when available. Excluded were women with follow-up <5years. Baseline data included validated questionnaire scores (UDI-6 question 3 (0-3), VAS Quality of Life, Incontinence Impact Questionnaire (IIQ-7)) and urodynamic study findings. Patients were followed with same questionnaires and three-dimensional ultrasound evaluating volume/configuration of MPQ. All three-dimensional ultrasound measurements were performed by the same imaging team blinded to clinical outcomes. Outcomes were evaluated in four groups based on prior SUI treatment. Success was defined as UDI-6 question 3 score of 0-1 and not requiring additional anti-incontinence therapy at the last visit after the last MPQ injection. RESULTS: From April 2011-December 2016, 106 patients (median age 67) met study criteria. Median follow-up time was 7.4years. Median MPQ injected was 5 mL. Overall success was 43%, with 54% successful after one injection and 46% requiring ≥2 injections. Across all groups, patients had improvement in Quality of Life and IIQ-7 Question 7 (frustration). Among the failure group, 17% opted for a secondary autologous sling procedure. CONCLUSION: MPQ demonstrated long-term favorable outcomes in a subset of women with SUI secondary to ISD.

Complete genomes of Limosilactobacillus portuensis and Limosilactobacillus vaginalis isolated from the urine of postmenopausal women.

There is frequent evidence that Limosilactobacillus vaginalis colonizes female genitourinary tracts but few reports of Limosilactobacillus portuensis. Their role in urinary tract infection (UTI) is unclear. We present the first complete genome of L. portuensis and a complete genome of L. vaginalis isolated from postmenopausal women with varying UTI histories.

Genetic and functional enrichments associated with Enterococcus faecalis isolated from the urinary tract.

IMPORTANCE: Urinary tract infection (UTI) is a global health issue that imposes a substantial burden on healthcare systems. Women are disproportionately affected by UTI, with >60% of women experiencing at least one UTI in their lifetime. UTIs can recur, particularly in postmenopausal women, leading to diminished quality of life and potentially life-threatening complications. Understanding how pathogens colonize and survive in the urinary tract is necessary to identify new therapeutic targets that are urgently needed due to rising rates of antimicrobial resistance. How Enterococcus faecalis, a bacterium commonly associated with UTI, adapts to the urinary tract remains understudied. Here, we generated a collection of high-quality closed genome assemblies of clinical urinary E. faecalis isolated from the urine of postmenopausal women that we used alongside detailed clinical metadata to perform a robust comparative genomic investigation of genetic factors that may be involved in E. faecalis survival in the urinary tract.

Characteristics of Nationwide Urinary Tract Infection (UTI) Visits by Age and Type II Diabetes Status in Women.

Background Through a national database search of office visits, we studied the contribution of two known risk factors for urinary tract infections (UTIs) in women: age and type 2 diabetes mellitus (T2DM). Methodology The National Ambulatory Medical Care Survey (NAMCS) database was queried for visits including a UTI diagnosis and a urine culture order. Data were included for all visits involving adult women for available years, 2014-2016 and 2018. Data on demographics, reason for visit, T2DM status, UTI workup, and UTI treatment were collected. Patients with Alzheimer's disease or chronic kidney disease were excluded. Descriptive statistics were displayed as weighted means with standard errors for continuous variables. The effect of age was compared based on a 65-year-old cutoff. Results One hundred sixty-seven surveyed visits were analyzed for the years 2014-2016 and 2018, representing an estimated 7.4 million visits nationwide. Women ≥65 years were more likely to be white, non-Hispanic/non-Latino, from the Midwest or West, from metropolitan areas, and on Medicare/Medicaid than their younger counterparts. T2DM and urinalysis rates did not significantly vary between the two age groups (7.7% vs. 14.6%, P = 0.3; 78% vs. 76%, P = 0.9, respectively). For urinalysis rates between patients with and without T2DM, there was no significant difference in the <65-year-old group (80% vs. 78%, P = 0.9) or the ≥65-year-old group (93% vs. 73%, P = 0.12). Antibiotic prescription rates were also similar for T2DM and non-T2DM patients (67% vs. 75%, P = 0.7). Conclusions Through a national database analysis, we reported the demographic and visit differences aged <65 years and ≥65 years who sought care for UTIs in the United States over a four-year period. T2DM rates and urinalysis did not vary between age groups, and urinalysis rates and antibiotic prescription rates did not vary between T2DM and non-T2DM groups in an age-dependent matter. More research is needed to understand the demographic makeup and risk factors of UTI patients across the nation.

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.

The distinct transcriptome of virulence-associated phylogenetic group B2 Escherichia coli.

Escherichia coli strains of phylogenetic group B2 are often associated with urinary tract infections (UTIs) and several other diseases. Recent genomic and transcriptomic analyses have not suggested or identified specific genes required for virulence, but have instead suggested multiple virulence strategies and complex host-pathogen interactions. Previous analyses have not compared core gene expression between phylogenetic groups or between pathogens and nonpathogens within phylogenetic groups. We compared the core gene expression of 35 strains from three phylogenetic groups that included both pathogens and nonpathogens after growth in a medium that allowed comparable growth of both types of strains. K-means clustering suggested a B2 cluster with 17 group B2 strains and two group A strains; an AD cluster with six group A strains, five group D strains and one B2 strain; and four outliers which included the highly studied model uropathogenic E. coli strains UTI89 and CFT073. Half of the core genes were differentially expressed between B2 and AD cluster strains, including transcripts of genes for all aspects of macromolecular synthesis-replication, transcription, translation, and peptidoglycan synthesis-energy metabolism, and environmental-sensing transcriptional regulators. Notably, core gene expression between nonpathogenic and uropathogenic transcriptomes within phylogenetic groups did not differ. If differences between pathogens and nonpathogens exist, then the differences do not require transcriptional reprogramming. In summary, B2 cluster strains have a distinct transcription pattern that involves hundreds of genes. We propose that this transcription pattern is one factor that contributes to virulence. IMPORTANCE Escherichia coli is a diverse species and an opportunistic pathogen that is associated with various diseases, such as urinary tract infections. When examined, phylogenetic group B2 strains are more often associated with these diseases, but the specific properties that contribute to their virulence are not known. From a comparative transcriptomic analysis, we found that group B2 strains grown in a nutrient-rich medium had a distinct transcription pattern, which is the first evidence that core gene expression differs between phylogenetic groups. Understanding the consequences of group B2 transcription pattern will provide important information on basic E. coli biology, the basis for E. coli virulence, and possibly for developing therapies for a majority of urinary tract infections and other group B2-associated diseases.