The impact of urine microbiota in patients with lower urinary tract symptoms.

INTRODUCTION: Inflammation and infection are causative factors of benign prostatic hyperplasia (BPH). Urine is not sterile, and urine microbiota identified by DNA sequencing can play an important role in the development of BPH and can influence the severity of lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: We collected mid-stream voided urine samples from BPH patients and control participants and stored them in a freezer at - 80 °C. All enrolled participants were requested to provide information about their clinical characteristics and complete the International Prostate Symptom Score (IPSS) questionnaire. Each step of the procedure, including the extraction of the genomic DNA from the urine samples; the amplification by polymerase chain reaction (PCR); PCR product quantification, mixing, and purification; DNA library preparation; and sequencing was performed with quality control (QC) measures. Alpha diversity was indicative of the species complexity within individual urine samples, and beta diversity analysis was used to evaluate the differences among the samples in terms of species complexity. Pearson's correlation analysis was performed to calculate the relationship between the clinical characteristics of the participants and the microbiota species in the urine samples. RESULTS: We enrolled 77 BPH patients and 30 control participants who reported no recent antibiotic usage. Old age, high IPSS and poor quality of life were observed in the participants of the BPH group. No significant differences were observed in the alpha diversity of the samples. In the beta diversity analysis, there was a significant difference between the microbiota in the samples of the BPH and control groups according to ANOSIM statistical analysis. On comparing the groups, the ten bacterial genera present in the samples of the BPH group in descending order of abundance were: Sphingomonas, Bacteroides, Lactobacillus, Streptococcus, Alcaligenes, Prevotella, Ruminococcaceae UCG-014, Escherichia_Shigella, Akkermansia, and Parabacteroides. Spearman's correlation analysis revealed that urine samples showing the presence of the bacterial genera Haemophilus, Staphylococcus, Dolosigranulum, Listeria, Phascolarctobacterium, Enhydrobacter, Bacillus, [Ruminococcus]torques, Faecalibacterium, and Finegoldia correlated with a high IPSS, and severe storage and voiding symptoms (P < 0.05). CONCLUSION: Our current study shows that dysbiosis of urine microbiota may be related to the development of BPH and the severity of LUTS. Further research targeting specific microbes to identify their role in the development of diseases is necessary and might provide novel diagnostic biomarkers and therapeutic options.

A multi-omic investigation of male lower urinary tract symptoms: Potential role for JC virus.

Male lower urinary tract symptoms (LUTS) comprise a common syndrome of aging that negatively impacts quality of life. The etiology of LUTS is multifactorial, involving benign prostatic hyperplasia, smooth muscle and neurologic dysfunction, inflammation, sexually transmitted infections, fibrosis, and potentially dysbiosis, but this aspect remains poorly explored. We investigated whether the presence of infectious agents in urine might be associated with LUTS by combining next-generation DNA sequencing for virus discovery, microbiome analysis for characterization of bacterial communities, and mass spectrometry-based metabolomics. In urine from 29 LUTS cases and 9 controls from Wisconsin, we found a statistically significant association between a diagnosis of LUTS and the presence of JC virus (JCV), a common neurotropic human polyomavirus (Polyomaviridae, Betapolyomavirus) linked to severe neurologic disease in rare cases. This association (based on metagenomics) was not borne out when specific polymerase chain reaction (PCR) testing was applied to this set of samples, likely due to the greater sensitivity of PCR. Interestingly, urine metabolomics analysis identified dysregulation of metabolites associated with key LUTS processes. Microbiome analysis found no evidence of microbial community dysbiosis in LUTS cases, but JCV-positive samples contained more Anaerococcus species, which are involved in polymicrobial infections of the urinary tract. Neither age nor body mass index were significantly associated with the presence of urinary JCV-in the initial group or in an additional, regionally distinct group. These data provide preliminary support the hypothesis that viruses such as JCV may play a role in the development or progression of LUTS, together with other infectious agents and host metabolic responses.

Changes in Bacterial Spectrum and Resistance Patterns Over Time in the Urine of Patients with Neurogenic Lower Urinary Tract Dysfunction Due to Spinal Cord Injury.

INTRODUCTION: Urinary tract infections (UTI) are among the most common complications in persons with neurogenic lower urinary tract dysfunction (NLUTD) due to spinal cord injury (SCI). As both asymptomatic bacteriuria and UTI are frequently treated with antibiotics, concerns about multidrug resistance arise. Therefore, we analyzed the bacterial spectrum in the urine and the resistance patterns of the strains over time in patients with NLUTD due to SCI. METHODS: In a systematic chart review, we identified all microbiologic urine test results including resistance patterns of persons with SCI in a tertiary referral hospital at 2 time periods (2010-2011 and 2017-2018). We assessed the frequency of the bacterial strains, the resistance patterns of the 5 most frequent bacteria, and the use of antibiotics for in- as well as for outpatients. RESULTS: From 2010 to 2011, 1,308 (outpatients) and 2,479 (inpatients) bacterial strains were detected in the urinalyses performed; these numbers rose to 3,162 and 6,112 during 2017-2018, respectively. The most frequently detected bacteria during both time periods were Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae/variicola, Streptococcus viridans, Pseudomonas aeruginosa, and coagulase negative Staphylococci. Fluoroquinolones were the most frequently used antibiotics during both time periods. Despite its frequent use, no relevant increase in resistance against fluoroquinolones was detected. The most prominent increase in resistance appeared in E. coli against amocixillin/clavulanic acid in inpatients (from 26.0 to 38.5%). DISCUSSION AND CONCLUSIONS: Although fluoroquinolones were used frequently, we did not observe an increased resistance against these antibiotics over time in the urine of patients with SCI.

Aerococcus urinae Isolated from Women with Lower Urinary Tract Symptoms: In Vitro Aggregation and Genome Analysis.

Aerococcus urinae is increasingly recognized as a potentially significant urinary tract bacterium. A. urinae has been isolated from urine collected from both males and females with a wide range of clinical conditions, including urinary tract infection (UTI), urgency urinary incontinence (UUI), and overactive bladder (OAB). A. urinae is of particular clinical concern because it is highly resistant to many antibiotics and, when undiagnosed, can cause invasive and life-threatening bacteremia, sepsis, or soft tissue infections. Previous genomic characterization studies have examined A. urinae strains isolated from patients experiencing UTI episodes. Here, we analyzed the genomes of A. urinae strains isolated as part of the urinary microbiome from patients with UUI or OAB. Furthermore, we report that certain A. urinae strains exhibit aggregative in vitro phenotypes, including flocking, which can be modified by various growth medium conditions. Finally, we performed in-depth genomic comparisons to identify pathways that distinguish flocking and nonflocking strains.IMPORTANCEAerococcus urinae is a urinary bacterium of emerging clinical interest. Here, we explored the ability of 24 strains of A. urinae isolated from women with lower urinary tract symptoms to display aggregation phenotypes in vitro We sequenced and analyzed the genomes of these A. urinae strains. We performed functional genomic analyses to determine whether the in vitro hyperflocking aggregation phenotype displayed by certain A. urinae strains was related to the presence or absence of certain pathways. Our findings demonstrate that A. urinae strains have different propensities to display aggregative properties in vitro and suggest a potential association between phylogeny and flocking.

Male Bladder Microbiome Relates to Lower Urinary Tract Symptoms.

BACKGROUND: In women, compelling evidence associates lower urinary tract microbiota (LUTM) with lower urinary tract symptoms (LUTS); a similar association in men with benign prostate enlargement (BPE) is not established. OBJECTIVE: To determine whether associations exist between LUTM and LUTS. DESIGN, SETTING, AND PARTICIPANTS: Forty-nine male volunteers, aged 40-85 yr, were recruited from one academic tertiary care center. Twenty-eight patients undergoing BPE/LUTS surgery and 21 undergoing non-BPE/LUTS surgery were stratified by International Prostate Symptom Score (IPSS), and paired voided/catheterized urine specimens were collected for expanded quantitative urine culture (EQUC) and 16S ribosomal RNA gene sequencing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary and secondary outcomes were presence of detectable LUTM and specific bacterial members of the LUTM, respectively. Baseline data were compared. Univariable logistic regression models were used to calculate odds ratios (ORs) for IPSS category associated with the presence of bladder microbiota. Relative LUTM proportions were compared with IPSS using chi-square tests. RESULTS AND LIMITATIONS: Thirty-nine percent of catheterized and 98% of voided specimens contained LUTM. Catheterized and voided LUTM differed significantly. LUTM was detected in catheterized urine of 22.2% of men with mild LUTS, 30.0% with moderate LUTS, and 57.1% with severe LUTS (p=0.024). Increased IPSS category was associated with significantly higher odds of detectable bacteria (OR: 2.21, 95% confidence interval: 1.09-4.49). Small sample size limited this study, making it unable to identify significant differences in specific bacterial taxa based on IPSS. CONCLUSIONS: Voided urine does not adequately characterize the male bladder microbiome. In males with and without BPE, IPSS severity was associated with detectable bacteria in catheterized urine, which samples the bladder. Additional studies are needed to identify specific bladder bacteria associated with LUTS. PATIENT SUMMARY: To study bladder bacteria, urine should be collected with a catheter. Men with severe urinary symptoms are more likely to have detectable bladder bacteria than those with less severe symptoms.

The Role of Urinary Microbiota in Lower Urinary Tract Dysfunction: A Systematic Review.

CONTEXT: Until 2012, the urinary tract of healthy individuals was considered to be sterile. The advent of metagenomic sequencing revealed a unique urinary microbiota (UM). This paradigm shift appears to have prolific implications in the etiology of several functional lower urinary tract (LUT) disorders. OBJECTIVE: To systematically summarize recent data on the role of UM in LUT dysfunction. EVIDENCE ACQUISITION: We performed a critical review according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. We conducted a search on PubMed/MEDLINE and SCOPUS with the following MESH terms/keywords: "Microbiome OR Microbiota AND (urinary disorder OR urinary tract symptom OR overactive bladder OR urinary incontinence OR interstitial cystitis OR chronic prostatitis)." The range of search was placed between January 2010 and April 2018, and articles with no full text available or those not written in English were excluded. All retrieved papers were first reviewed by title and abstract, yielding a total of 303 papers. Additional manuscripts, such as those referenced by reviews, were further included. Thirty-six publications were included. EVIDENCE SYNTHESIS: Analysis by 16S rRNA sequence and expanded quantitative urine culture provided evidence for the presence of live bacteria in urine, nondetectable by standard culture protocols. Moreover, differences in the UM between healthy individuals and patients with LUT dysfunction were demonstrated. CONCLUSIONS: In the near future, urologists must consider urinary dysbiosis as a possible cause of different functional LUT disorders, with potential clinical implications in their diagnosis and treatment. PATIENT SUMMARY: Development of metagenomic sequencing revealed a unique urinary microbiota nondetectable by standard culture protocols. This systematic review summarizing recent data on the role of urinary microbiota in lower urinary tract (LUT) dysfunction supports urinary dysbiosis as a possible cause of different functional LUT disorders.

The effect of the urinary and faecal microbiota on lower urinary tract symptoms measured by the International Prostate Symptom Score: analysis utilising next-generation sequencing.

OBJECTIVE: To examine the correlation between urinary and faecal microbial profiles and the different aspects of lower urinary tract symptoms (LUTS) in men, as there is accumulating evidence that variations in the human microbiota may promote different benign disease conditions. PATIENTS AND METHODS: We extracted total DNA from urine and faecal samples of a group of men, under an Institutional Review Board-approved protocol. At the same time, International Prostate Symptom Score (IPSS) data were collected. We then amplified the extracted DNA and sequenced it using bacterial 16S ribosomal RNA gene high-throughput next-generation sequencing platform, and analysed the microbial profiles for taxonomy to examine the correlation between the different operational taxonomy units (OTUs) and LUTS represented by the total IPSS, the different symptom levels of the IPSS (mild, moderate, and severe) and its subcomponents of storage, nocturia, voiding, and bother. RESULTS: We included 30 patients (60 samples; one urine and one faecal per patient). In all, 48 faecal OTUs showed a significant correlation with one or more of the IPSS components; 27 with nocturia, 19 with bother, 16 with storage symptoms, and nine with voiding symptoms. The most substantial negative (protective) correlation was between Lachnospiraceae Blautia, a bacteria that increases the availability of gut anxiolytic and antidepressant short-chain fatty acids, and bother (correlation coefficient 0.702; P = 0.001). The abundance of L. Blautia continued to have a protective correlation against LUTS when looking at the different levels of IPSS severity (moderate and severe vs mild, correlation coefficient 0.6132; P = 0.002). Ten unique urinary OTUs showed significant correlation with LUTS; eight with nocturia, one with bother, three with storage, and one with voiding, but no faecal OUT had more than a low correlation with the outcomes of interest in this study. CONCLUSIONS: Our prospective work finds a plausible correlation between L. Blautia and LUTS. Additional studies are needed to determine if the correlations found in the present research are applicable to the general population of patients affected by LUTS.

[Efficacy of 5-reductase inhibitors in the treatment of lower urinary tract symptoms in patients with benign prostatic hyperplasia].

In the treatment of lower urinary tract in combination with benign prostatic hyperplasia, alpha-blockers are most often prescribed, but in certain cases, the appointment of 5-reductase inhibitors is justified. This article analyzes relevant studies of recent years regarding the validity of the use of dutasteride (Gardium) 0.5 mg per day. Dutasteride can effectively reduce the total score of IPSS to 30%. It increases a volumetric urine flow rate 2-3 ml/sec, significantly reduces the chance of acute urinary retention in 70-88% in various studies, and reduces the frequency of hospitalization by 66%. Dutasteride also increases the likelihood of timely diagnosis of prostate cancer by 23%. Erectile dysfunction is a common side effect, serving as a reason for refusal of therapy is erectile dysfunction, which occurs in 16% of cases, and the probability of which is the highest in the first months during conservative therapy.

Relationship between alterations of urinary microbiota and cultured negative lower urinary tract symptoms in female type 2 diabetes patients.

BACKGROUND: Lower urinary tract symptoms (LUTS) is the most common complication of diabetes. However, the underlying pathogenesis of cultured negative LUTS (cn-LUTS) in diabetic patients has not been well understood. Numerous evidence indicates that urinary dysbiosis is related to urologic disorders. We aim to study alterations of the urinary microbiota of cn-LUTS in type 2 diabetes (T2D) patients. METHODS: Female T2D patients and controls were recruited and requested to finish the American Urological Association Symptom Index. Mid-stream urine was collected for culturing and extracting DNA. Microbial diversity and composition were analyzed by targeting to 16S rDNA. Linear discriminant analysis effect size (LEfSe) was carried out to identify significantly different bacteria. RESULTS: 32 female T2D patients and 26 controls were enrolled. No significant differences in alpha diversity were observed between patients and controls. However, statistically decreased richness (ACE index and Chao 1 index, 85.52(13.75, 204.84) vs. 129.82(63.89, 280.30) and 83.86(11.00, 210.77) vs. 125.19(62.00, 251.77), P = 0.005; Observed Species, 76(10, 175) vs. 98(54, 234), P = 0.011) and decreased species diversity (Shannon index, 1.37(0.04, 3.48) vs. 2.09(0.98, 3.43), P = 0.033; Simpson index, 0.46 (0.06, 0.99) vs. 0.23(0.07, 0.64), P = 0.029) were shown in moderate-to-severe LUTS group and high Hemoglobin A1c group, respectively. A significant difference of beta diversity was found between T2D patients and controls and T2D patients with different severity of cn-LUTS as well as the different level of Hemoglobin A1c. LEfSe revealed that 10 genera (e.g., Escherichia-Shigella and Klebsiella) were increased and 7 genera were decreasing in T2D patients, 3 genera (e.g., Escherichia-Shigella and Campylobacter) were increased and 16 genera (e.g., Prevotella) were reduced in moderate-to-severe LUTS group, 2 genera (Escherichia-Shigella and Lactobacillus) were over-represented and 10 genera (e.g., Prevotella) were under-represented in high Hemoglobin A1c group. Finally, Hemoglobin A1c was found positively correlated with the total score of the American Urological Association Symptom Index (r = 0.509, P = 0.003). CONCLUSIONS: Urinary dysbiosis may be related to cn-LUTS in female T2D patients. A better understanding of urinary microbiota in the development and progression of cn-LUTS in female T2D patients was necessary. The severity of cn-LUTS was correlated to hyperglycemia and chronic hyperglycemia might induce or promote cn-LUTS by influencing urinary microbiota.

Sanjin tablets for acute uncomplicated lower urinary tract infection (syndrome of dampness-heat in the lower jiao): protocol for randomized, double-blind, double-dummy, parallel control of positive drug, multicenter clinical trial.

BACKGROUND: Acute uncomplicated lower urinary tract infection (UTI) is one of the most common bacterial infections. Patients usually present with dysuria, urinary urgency, urinary frequency, and suprapubic pain or tenderness. Approximately 150 million people are diagnosed with UTI each year worldwide. The high recurrence rate of lower UTI is a common problem of clinical treatment. The misuse of antibiotics has led to the emergence of a number of resistant bacterial strains. Thus, traditional Chinese medicine is considered as an alternative option for treating acute uncomplicated lower UTI. Thus, this study aims to evaluate the efficacy and safety of Sanjin tablets (SJT) for the treatment of acute uncomplicated lower UTI, explore whether SJT can reduce or substitute the use of antibiotics, and reduce the recurrence rate in the treatment of acute uncomplicated lower UTI. METHODS/DESIGN: In this study, a randomized, double-blind, double-dummy, parallel control of positive drug, multicenter clinical study will be established. A total of 252 patients with acute uncomplicated lower UTI (syndrome of dampness-heat in the lower jiao) will be randomly allocated in the ratio of 1:1:1 to three groups: experimental group; control group 1; and control group 2. The experimental group receives Sanjin tablets plus levofloxacin tablets (LT) placebo; the control group 1 receives LT plus SJT placebo; and the control group 2 receives SJT plus LT on the first five days, SJT plus LT placebo on the last two days. Each group will be treated for seven days and followed-up 1-2 times. The primary outcome measures of effective rate and recurrence rate are symptoms. Secondary outcome measures of effective rate and recurrence rate are the urine leukocytes, bacteriology examination, and safety assessment. Outcomes will be assessed at baseline and after treatment. DISCUSSION: This study protocol will provide the research data of efficacy and safety of SJT for the treatment of acute uncomplicated lower UTI. The first aim is to determine whether Sanjin tablets can reduce the use of antibiotics; the second aim is to determine whether Sanjin tablets can substitute the use of antibiotics. The recurrence rate will be assessed after cured to determine whether SJT can reduce the recurrence rate. The results of this study will improve the rational use of drugs, especially the rational application of antibiotics. It will also enable safety evaluation from laboratory indices and adverse events, which will provide reliable evidence for clinical treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03658291 . Registered on 4 September 2018.

The Urinary Tract Microbiome: The Answer to All Our Open Questions?

CONTEXT: The dogma of a sterile urinary tract persisted for over a century. With the advances in new high-throughput sequencing technologies and modified culture protocols for microbiome research, we have discovered a variable microbial spectrum in the urinary tract. Its relevance for health and disease is now under investigation. OBJECTIVE: To present the latest insights into the role of the urinary tract microbiome in functional disorders. EVIDENCE ACQUISITION: Medline, PubMed, the Cochrane database, and Embase were screened for randomised controlled trials, clinical trials, and reviews on the urinary tract microbiome. EVIDENCE SYNTHESIS: The urinary tract is not sterile. Every individual harbours a complex microbial network in the urinary tract that is exposed to internal and external factors. Any imbalance in this network is likely to contribute to the development of lower urinary tract symptoms. Functional disorders such as interstitial cystitis, urinary urge incontinence, and chronic prostatitis/chronic pelvic pain syndrome, none of which include a bacterial origin for diagnosis, show features of an altered microbiome with specific dominating urotypes in contrast to urine from asymptomatic healthy individuals. The growing insights into the impact of the urinary microbiome on these entities may help in gaining a deeper understanding of the condition and may provide guidance for optimised management. CONCLUSIONS: The urinary tract is not sterile. The discovery of the urinary microbiome suggests that any imbalance may have a relevant role in the development of symptoms in functional disorders. PATIENT SUMMARY: The urinary tract is naturally colonised with a specific microbial spectrum for which impairment may cause bothersome symptoms.

Is the microbiome influencing patient care in lower urinary tract dysfunction? Report from the ICI-RS 2017.

AIMS: This report sets out to consider the role of the microbiome within the bladder to provide clinicians with knowledge on this specific area of research and recommend potential topics for further studies. METHODS: This is a report from the Plenary 6: Is the microbiome influencing patient care in lower urinary tract dysfunction (LUTD)? RESULTS: There appear to be complex associations between microbial presence in the bladder and lower urinary tract symptoms. There appears to be a greater role of bacteria in the development of overactive bladder symptoms than previously thought with bacteria such as Gardnerella highlighted to be more prevalent in women with urgency urinary incontinence. Some species of Lactobacillus have also been found to play a protective role in both overactive bladder syndrome and bladder pain syndrome. CONCLUSIONS: The bladder is a reservoir for bacterial colonization and what was previously thought to be a sterile environment now seems to be a complex interaction of both multiple protective and pathogenic bacterial species than can give rise to lower urinary tract symptoms. While most clinicians use antibacterial agents as part of treatment regimens, and evidence does suggest a role of antibacterial therapies in treatment of LUTS, this remains a far from an ideal solution.

Recalcitrant chronic bladder pain and recurrent cystitis but negative urinalysis: What should we do?

PURPOSE: Lower urinary tract symptoms (LUTS) may be associated with chronic urinary tract infection (UTI) undetected by routine diagnostic tests. Antimicrobial therapy might confer benefit for these patients. MATERIALS AND METHODS: Over 10 years, we treated patients with chronic LUTS. Pyuria was adopted as the principal biomarker of infection. Urinary leucocyte counts were recorded from microscopy of fresh midstream urine (MSU) samples. Antibiotics were prescribed and the prescription adjusted to achieve a measurable clinical response and a reduction in pyuria. RESULTS: We treated 624 women [mean age = 53.4 years; standard deviation (SD) = 18] with chronic LUTS and pyuria. Mean duration of symptoms prior to presentation was 6.5 years. Only 16% of MSU cultures submitted were positive (≥105 cfu ml-1). Mean treatment length was 383 days [SD = 347; 95% confidence interval (CI) = 337-428]. Treatment was associated with a reduction in total LUTS (F = 98; p = 0.0001), 24-h frequency (F = 75; p = 0.0001), urinary urgency (F = 90; p = 0.0001), lower urinary tract pain (F = 108; p = 0.0001), voiding symptoms (F = 10; p = 0.002), and pyuria (F = 15.4; p = 0.0001). Full-dose first-generation antibiotics for UTI, such as cefalexin, nitrofurantoin, or trimethoprim, were combined with methenamine hippurate. We recorded 475 adverse events (AEs) during 273,762 treatment days. There was only one serious adverse event (SAE). We observed no increase in the proportion of resistant bacterial isolates. CONCLUSION: This large case series demonstrates that patients with chronic LUTS and pyuria experience symptom regression and a reduction in urinary tract inflammation associated with antimicrobial therapy. Disease regression was achieved with a low frequency of AEs. These results provide preliminary data to inform a future randomized controlled trial (RCT).

Lower urinary tract symptoms that predict microscopic pyuria.

INTRODUCTION AND HYPOTHESIS: Urinary dipsticks and culture analyses of a mid-stream urine specimen (MSU) at 105 cfu ml-1 of a known urinary pathogen are considered the gold standard investigations for diagnosing urinary tract infection (UTI). However, the reliability of these tests has been much criticised and they may mislead. It is now widely accepted that pyuria (≥1 WBC µl-1) detected by microscopy of a fresh unspun, unstained specimen of urine is the best biological indicator of UTI available. We aimed to scrutinise the greater potential of symptoms analysis in detecting pyuria and UTI. METHODS: Lower urinary tract symptom (LUTS) descriptions were collected from patients with chronic lower urinary tract symptoms referred to a tertiary referral unit. The symptoms informed a 39-question inventory, grouped into storage, voiding, stress incontinence and pain symptoms. All questions sought a binary yes or no response. A bespoke software package was developed to collect the data. The study was powered to a sample of at least 1,990 patients, with sufficient power to analyse 39 symptoms in a linear model with an effect size of Cohen's f2 = 0.02, type 1 error probability = 0.05; and power (1-ß); 95% where ß is the probability of type 2 error). The inventory was administered to 2,050 female patients between August 2004 and November 2011. The data were collated and the following properties assessed: internal consistency, test-retest reliability, inter-observer reliability, internal responsiveness, external responsiveness, construct validity analysis and a comparison with the International Consultation on Incontinence Modular Questionnaire for female lower urinary tract symptoms (ICIQ-FLUTS). The dependent variable used as a surrogate marker of UTI was microscopic pyuria. An MSU sample was sent for routine culture. RESULTS: The symptoms proved reliable predictors of microscopic pyuria. In particular, voiding symptoms correlated well with microscopic pyuria (χ2 = 88, df = 1, p < 0.001). The symptom inventory has significant psychometric characteristics as below: test-retest reliability: Cronbach's alpha was 0.981; inter-observer reliability, Cronbach's alpha was 0.995, internal responsiveness F = 221, p < 0.001, external responsiveness F = 359, df = 5, p < 0.001. The correlation coefficients for the domains of the ICIQ-FLUTS were around R = 0.5, p < 0.001. CONCLUSION: This symptoms score performed well on the standard, psychometric validation. The score changed in response to treatment and in a direction appropriate to the changes in microscopic pyuria. It correlated with measures of quality of life. It would seem to make a good candidate for monitoring treatment progress in ordinary clinical practice.

The urinary microbiome and its contribution to lower urinary tract symptoms; ICI-RS 2015.

AIMS: The microbiome is the term used for the symbiotic microbial colonisation of healthy organs. Studies have found bacterial identifiers within voided urine which is apparently sterile on conventional laboratory culture, and accordingly there may be health and disease implications. METHODS: The International Consultation on Incontinence Research Society (ICI-RS) established a literature review and expert consensus discussion focussed on the increasing awareness of the urinary microbiome, and potential research priorities. RESULTS: The consensus considered the discrepancy between findings of conventional clinical microbiology methods, which generally rely on culture parameters predisposed towards certain "expected" organisms. Discrepancy between selective culture and RNA sequencing to study species-specific 16S ribosomal RNA is increasingly clear, and highlights the possibility that protective or harmful bacteria may be overlooked where microbiological methods are selective. There are now strong signals of the existence of a "core" urinary microbiome for the human urinary tract, particularly emerging with ageing. The consensus reviewed the potential relationship between a patient's microbiome and lower urinary tract dysfunction, whether low-count bacteriuria may be clinically significant and mechanisms which could associate micro-organisms with lower urinary tract symptoms. CONCLUSIONS: Key research priorities identified include the need to establish the scope of microbiome across the range of normality and clinical presentations, and gain consensus on testing protocols. Proteomics to study enzymatic and other functions may be necessary, since different bacteria may have overlapping phenotype. Longitudinal studies into risk factors for exposure, cumulative risk, and emergence of disease need to undertaken. Neurourol. Urodynam. 36:850-853, 2017. © 2017 Wiley Periodicals, Inc.

Gross Hematuria Is More Common in Male and Older Patients with Renal Tuberculosis in China: A Single-Center 15-Year Clinical Experience.

OBJECTIVES: This study aimed to investigate the clinical features of renal tuberculosis and identify the age- and gender-related differences. METHODS: A total of 419 patients at the Peking University First Hospital from January 2000 to July 2015 were retrospectively reviewed. Data on demographic characteristics, clinical presentation, complications, laboratory results, radiologic imaging, surgical procedures, and pathology features were collected and compared between genders and 3 different age groups (under 40 years, 41-60, years and over 60 years). RESULTS: The most common local presentations were lower urinary tract symptoms (65.2%), flank pain (37.9%), and gross hematuria (26.3%). Constitutional symptoms were also observed in 38.9% of the patients. Gross hematuria was more common in male patients (32.2%) and older patients (45.5%). Flank pain was more common in female patients (43.6%). Patients younger than 40 years of age had lower frequencies of calcification of the urinary tract (22.2%) and kidney atrophy (4.2%) in CT. In the postoperative pathological reports, atrophy (35.9%) and fibrosis (38.5%) were found to be significantly more common in older patients. CONCLUSIONS: While gross hematuria is more prevalent in older patients and male patients, flank pain is more common in female patients. Radiological and pathological features including calcification of the urinary tract, fibrosis, and kidney atrophy are more common in older patients.

The human urinary microbiome and how it relates to urogynecology.

INTRODUCTION AND HYPOTHESIS: Recent studies applying molecular techniques have demonstrated the presence of a urinary microbiota not detected by standard microbiological techniques. These have been found in the urine of healthy individuals and in those suffering from clinical symptoms. The present article reviews the findings of these studies to date, describing the molecular techniques, and specifically outlining any differences in microbiomes in relation to urogynecological disease. Further, the role of commensal bacteria in the lower urinary tract is considered. METHODS: An extensive literature search was conducted to identify articles on the microbiome of the female urinary tract in health and disease. We searched the electronic meta-databases Ovid MEDLINE® 1946-2015 and Embase 1974-2015. The keywords "microbiome, microbiota, bacterial colonization, microbiology, commensal bacteria, and bacteriuria" were searched in combination with "lower urinary tract symptoms, urogenital symptoms, urinary tract infection, overactive bladder and urinary incontinence." A total of 426 papers were retrieved; 33 were included in this paper. RESULTS: The microbiome of the female lower urinary tract shows variance between individuals and between age groups. There are significant differences between the microbiota in the lower urinary tract of individuals with urological symptoms and those without, relating to type and proportion of commensal Lactobacillus spp. There is only weak evidence to suggest that Lactobacillus might be applied as a therapeutic measure. CONCLUSIONS: It is still unclear what role microbiota plays in female urinary tract health. The discovery of bacteria in the urine of healthy individuals may have implications for future therapies for lower urinary tract symptoms.

Urinary tract infections in women with urogynaecological symptoms.

PURPOSE OF REVIEW: Urinary tract infections are common in the field of urogynaecology. Women with persistent urinary symptoms seem more likely to have bacteriuria despite negative cultures. In this review, we will give an overview of the recent insights on the relationship between urinary tract infection and persistent urinary symptoms and possible new therapeutic options. RECENT FINDINGS: Recently published articles evaluated the prevalence of low-count bacteriuria (≥10 CFU/ml) or intracellular bacterial communities in women with overactive bladder symptoms (OAB). Differences in urinary microbioma observed in women with and without OAB symptoms were evaluated. In the light of these findings, current screening strategies were discussed and alternative screening methods for bacteriuria developed. SUMMARY: Low-count bacteriuria (≥10 CFU/ml) seems to be more prevalent in women with OAB. Also intracellular bacterial communities are more commonly detected in these women. The microbioma found in women with urinary symptoms appeared to differ from healthy controls. The current screening methods might be insufficient as they are targeted at detecting uropathogenic Escherichia coli, mostly using a detection threshold of at least 10 CFU/ml and failing to detect intracellular bacterial communities. Studies evaluating the efficacy of treating women with low-count bacteriuria are limited but promising.

Intracellular Bacterial Communities: A Potential Etiology for Chronic Lower Urinary Tract Symptoms.

Patients with persistent lower urinary tract symptoms and negative urine cultures are often difficult to treat. Infection may go undetected in these patients because the concentrations of bacteria in their urine are beneath the threshold of standard urine culture techniques. Empiric treatment may result in temporary relief, followed by recurrent symptoms. Occult and recurrent urinary tract infection may be due to both invasion of the bladder wall by uropathogenic Escherichia coli and the formation of biofilm-like intracellular bacterial communities. This review examines emerging evidence for a role of intracellular bacterial communities in human infection.

Do patients who complain of lower urinary tract symptoms frequently have clinically significant pyuria?

There is still controversy about whether post-void residual (PVR) urine volume affects the onset of urinary tract infection (UTI). In addition, although male patients with lower urinary tract symptoms (LUTS) might potentially have PVR, the association between LUTS and UTI or asymptomatic pyuria with or without bacteriuria remains unclear. We studied the frequency of asymptomatic pyuria, with and without bacteriuria, in patients with LUTS without a previous history of urinary tract manipulation at the first visit and their sequential courses. This retrospective study was done by reviewing medical charts. A total of 453 male patients who complained of LUTS and visited our outpatient clinic in 2008 were included in this study. The frequency of pyuria, with or without bacteriuria, in this study at the first visit was 4.9%. The median PVR volumes at the initial examination were 79 ml in the 22 patients with pyuria and 22 ml in the 431 patients without pyuria. The difference of the PVR volume between the patients with pyuria and those without pyuria was statistically significant (p = 0.0095). Twelve patients were treated with alpha-blockers without antimicrobial chemotherapy and pyuria disappeared in 5 (41.7%) of them. However, the decrease in the rate of PVR was not significantly different between the patients with persisting pyuria and those without pyuria. A not negligible number of patients with LUTS had pyuria at the first visit; however, there was no febrile UTI in their clinical course even if they received no urological manipulation.