Dysbiosis of urine microbiota in obstructive urinary retention patients revealed by next-generation sequencing.

BACKGROUND: Urinary retention (UR) is a common urinary system disease can be caused by urinary tract obstruction with numerous reasons, however, the role of urine microbes in these disorders is still poorly understood. The aim of this study was to identify the urine microbial features of two common types of obstructive UR, caused by urinary stones or urinary tract tumors, with comparison to healthy controls. METHODS: Urine samples were collected from a cohort of 32 individuals with stone UR, 25 subjects with tumor UR and 25 healthy controls. The urine microbiome of all samples was analyzed using high-throughput 16S rRNA (16S ribosomal RNA) gene sequencing. RESULTS: We observed dramatically increased urine microbial richness and diversity in both obstructive UR groups compared to healthy controls. Despite different origins of UR, bacteria such as Pseudomonas, Acinetobacter and Sphingomonas were enriched, while Lactobacillus, Streptococcus, Gardnerella, Prevotella and Atopobium were decreased in both UR groups in comparison with healthy controls, exhibited an approximate urine microbial community and functional characteristics of two types of obstructive UR. Furthermore, disease classifiers were constructed using specific enriched genera in UR, which can distinguish stone UR or tumor UR patients from healthy controls with an accuracy of 92.29% and 97.96%, respectively. CONCLUSION: We presented comprehensive microbial landscapes of two common types of obstructive urinary retention and demonstrated that urine microbial features of these patients are significantly different from that of healthy people. The urine microbial signatures would shed light on the pathogenesis of these types of urinary retention and might be used as potential classification tools in the future.

The microbiome in urological diseases.

Due to the rapid development of next-generation sequencing, it has become possible to obtain information on the sequences of all genes in a specific microbiome. The detection of bacteria in patients with no urinary tract infections indicated that the dogma that "urine is sterile" was false, leading to active research regarding the roles of the urinary microbiome in the human urinary tract. Here, we present a review of the current literature regarding the role of the microbiome in urology.

Concomitant Antibiotic Use and Survival in Urothelial Carcinoma Treated with Atezolizumab.

Antibiotic effects on the gut microbiota may negatively impact survival with immune checkpoint inhibitors (ICIs). However, there is minimal evidence regarding whether antibiotic impacts are specific to ICIs or impacts in urothelial carcinoma (UC). In a post hoc analysis of IMvigor210 (single-arm atezolizumab) and IMvigor211 (phase III randomised trial of atezolizumab vs chemotherapy), the association between antibiotic use and overall survival (OS) and progression-free survival (PFS) was assessed via Cox proportional hazard analysis. Antibiotic use was defined as any antibiotic administration between 30 d prior to and 30 d after treatment initiation. Antibiotic use was associated with worse OS (n = 847, hazard ratio or HR [95% confidence interval {CI}] = 1.44 [1.19-1.73]) and PFS (1.24 [1.05-1.46]) with atezolizumab, but not chemotherapy (n = 415, 1.15 [0.91-1.46] and 1.09 [0.88-1.36], respectively). In the randomised cohort of IMvigor211, the OS treatment effect (HR [95% CI]) of atezolizumab versus chemotherapy was 0.95 (95% CI 0.71-1.25) for antibiotic users, compared with 0.73 (0.60-0.88) for nonusers (p[interaction] = 0.1). Similar associations were noted in the PD-L1 IC2/3 population. In conclusion, antibiotic use was associated with worse survival outcomes in UC patients treated with atezolizumab. The study does not justify a change in antibiotic selection for infections; however antibiotic overuse occurs in cancer care and this needs to be evaluated for ICIs. PATIENT SUMMARY: In this report from clinical trials IMvigor210 and IMvigor211, it was demonstrated that antibiotic use is consistently associated with worse survival in patients with urothelial carcinoma treated with atezolizumab. No antibiotic association was observed in patients treated with chemotherapy, suggesting that antibiotics may specifically reduce the effectiveness of cancer immunotherapies. Future research will continue to explore the effect of antibiotics on other immune checkpoint inhibitors and confirm whether immune checkpoint inhibitors remain the treatment of choice in cancer patients requiring antibiotics.

Risk of infection in patients undergoing urologic surgery based on the presence of asymptomatic bacteriuria: A prospective study.

BACKGROUND: Treatment of asymptomatic bacteriuria (ASB) is recommended in pregnant women and prior to urologic procedures with anticipated mucosal disruption. However, there is still insufficient evidence of the usefulness of treating ASB prior to urologic procedures. Therefore, the aim of this study was to ascertain the risk of infections in patients undergoing urologic surgery based on the presence of ASB. METHODS: We conducted a cohort study among patients undergoing urologic surgery at a single center located in Medellín, Colombia. All patients were screened for ASB prior to their procedures. Patients were evaluated for the development of any postoperative infectious complications for up to 30 days after the procedure. RESULTS: A total of 149 patients were included in this cohort. Incidence of ASB was 14.8%. Thirteen patients (8.72%) developed infectious complications: 3 (13.64%) with ASB and 10 (7.87%) without ABS. Factors associated with postoperative infectious complications included urologic cancers (hazard ratio [HR], 5.26; 95% confidence intervals [CI], 1.24-22.37), urologic interventions in the preceding 3 months (HR, 3.72; 95% CI, 1.02-13.51), and use of antibiotics 3 months prior to surgery (HR, 3.83; 95% CI, 1.01-15.49). Presence of ASB was not associated with postsurgical infectious complications (HR, 1.02; 95% CI, 0.26-3.96). CONCLUSIONS: There was no association between ASB and postoperative infectious complications. There were other factors associated with infectious complications, such as urologic cancer, previous history of urologic manipulation, and antibiotic use.

Factors associated with multidrug-resistant bacteria in a cohort of patients with asymptomatic bacteriuria who underwent urological surgery.

BACKGROUND: Although the factors associated to bacterial resistance in patients with asymptomatic bacteriuria (ASB) have been studied in pregnant, fertile age women, patients with spinal cord injury, and those with urogynecological disorders, nothing is known about the factors associated with multidrug-resistant (MDR) bacteria in patients with ASB and planned urological procedures. This study therefore sought to identify the sociodemographic and clinical factors associated with MDR bacteria in a cohort of patients with ASB scheduled for urological procedures. METHODS: We conducted a nested case-control study on a cohort of patients with ASB and planned urological procedures at 3 Colombian medical centers. Cases were patients with MDR bacteria and controls were patients without MDR bacteria. RESULTS: A total of 184 patients were included, 41.8% (n = 77) of whom presented ASB with MDR bacteria. The factors linking ASB with MDR bacteria were: advanced age (odds ratio, 1.03; 95% confidence interval, 1.01-1.06) and hospitalization within the 3-month period before surgery (odds ratio, 2.35; 95% confidence interval, 1.08-5.21). CONCLUSIONS: Bacterial resistance is frequent among patients with ASB and planned urological procedures. Advanced age and prior hospitalization should be borne in mind for patients with planned urological procedures because they are factors associated with the presence of MDR bacteria.

Bacterial urinary tract infections associated with transitional cell carcinoma in dogs.

BACKGROUND: Urinary tract infections (UTI) are believed to be common in dogs with transitional cell carcinoma (TCC), but incidence and contributing factors have not been reported. OBJECTIVES: To determine the frequency and bacterial agents associated with UTI in dogs with TCC and define contributing factors. ANIMALS: Eighty-five dogs with a history of urogenital TCC undergoing treatment with chemotherapy that had at least 1 urine culture performed. METHODS: Medical records and culture results were retrospectively reviewed and ultrasound images were reviewed when available. Clinical factors were evaluated statistically for association with positive culture. RESULTS: Fifty-five percent (47/85) of dogs had at least 1 positive culture during the course of treatment. Female dogs (80%, 40/50) were more likely than male dogs (29%, 10/35) to have at least 1 positive culture. Ultrasound examination determined that female dogs were more likely to have urethral (74%, 31/42) or trigonal tumor involvement (71%, 30/42) compared to male dogs (32%, 9/28 and 43%, 12/28, respectively). The most commonly isolated organisms were Staphylococcus spp. (23.9%, 29/121) and Escherichia coli (19.8%, 24/121). Dogs with urethral involvement of TCC were significantly more likely to have at least 1 positive culture than dogs without urethral involvement (75%, 30/40 versus 30%, 9/30). CONCLUSIONS: Urinary tract infection is common in dogs with TCC highlighting the importance of regular monitoring for bacterial cystitis in dogs with TCC. In addition, clinical factors such as tumor location and sex may be predictive of positive culture and can help clinicians assess the risk of UTI.

Resistant gram-negative infections in the outpatient setting in Latin America.

Latin America has a high rate of community-associated infections caused by multidrug-resistant Enterobacteriaceae relative to other world regions. A review of the literature over the last 10 years indicates that urinary tract infections (UTIs) by Escherichia coli, and intra-abdominal infections (IAIs) by E. coli and Klebsiella pneumoniae, were characterized by high rates of resistance to trimethoprim/sulfamethoxazole, quinolones, and second-generation cephalosporins, and by low levels of resistance to aminoglycosides, nitrofurantoin, and fosfomycin. In addition, preliminary data indicate an increase in IAIs by Enterobacteriaceae producing extended-spectrum ß-lactamases, with reduced susceptibilities to third- and fourth-generation cephalosporins. Primary-care physicians in Latin America should recognize the public health threat associated with UTIs and IAIs by resistant Gram-negative bacteria. As the number of therapeutic options become limited, we recommend that antimicrobial prescribing be guided by infection severity, established patient risk factors for multidrug-resistant infections, acquaintance with local antimicrobial susceptibility data, and culture collection.

Urinary tract infection increases subsequent urinary tract cancer risk: a population-based cohort study.

This study examines the possible association between urinary tract infection (UTI) and urinary tract cancer (UTC). Data from the National Health Insurance system of Taiwan were used for the analysis. The UTI cohort included 70 116 patients who were diagnosed and recruited between 1997 and 2010. Each patient was randomly frequency-matched with two people without UTI from the general population based on their age, sex, and month of UTI diagnosis. Cox's proportional hazard regression analysis was used to estimate the effects of UTI on UTC risk until the end of follow-up on December 31, 2010. Patients with UTI had a significantly higher risk of developing UTC than healthy people (adjusted hazard ratio, 4.66; 95% confidence interval, 3.55-6.10). Further analyses indicated that risks are potentially related to the level of the lesion site. This study indicated that patients with UTI had a higher risk of developing UTC.

Emergence of extended-spectrum beta-lactamase-producing Escherichia coli in community hospitals throughout North Carolina: a harbinger of a wider problem in the United States?

Community-onset urinary tract infections due to extended-spectrum beta-lactamase-producing Escherichia coli have become increasingly common worldwide but have been considered to be uncommon infections in the United States. We report the emergence and subsequent rapid increase in the incidence of these infections in community hospitals throughout North Carolina since 2006.

BK virus infection of the human urinary tract.

By screening consecutive autopsy cases with an antibody that recognizes human polyomaviruses, we found a case of malignant lymphoma in which the virus infection was confined to epithelia of the renal calyces, renal pelvis, ureter, and urinary bladder. The virus was confirmed as BK virus by a specific monoclonal antibody against BK virus T antigen, and numerous virus particles were identified by electron microscopy. The results showed that BK virus is a human urotheliotrophic virus.

Presence and physical state of HPV DNA in prostate and urinary-tract tissues.

Neoplastic and non-neoplastic tissues from the urinary tract and the prostate were analyzed for the presence of human papillomavirus (HPV) DNA. The analysis was performed by PCR using primers specific for HPV 6/11 and 16. HPV DNA was present in bladder, ureter, kidney and prostate, with percentages ranging between 46% and 87%. Benign and oncogenic HPV types were detected with similar frequencies both in non-neoplastic and in neoplastic biopsies, and HPV 16 was not preferentially associated with malignant lesions. In all instances, small amounts of HPV DNA were present in the tissues, suggesting the absence of productive infection. Analysis of the physical state of HPV DNA performed by 2-dimensional gel electrophoresis and Southern blot hybridization revealed that HPV 16 DNA harbored in the urinary tract can be integrated also in non-neoplastic tissues. The results indicate that HPV 16 does not seem to be associated with urinary-tract and prostate oncogenesis, but that these tissues may represent an important reservoir for the transmission of HPV types normally infecting the genital tract.

Longitudinal study of human papillomavirus infection of the female urogenital tract by in situ hybridization.

The recurrence and/or persistence of human papillomavirus (HPV)-associated lesions constitute a well-recognized clinical problem; yet, few studies have demonstrated and typed the HPV within these recurrence lesions. A patient with a 17-year history of anogenital condylomata presented with an unusual bladder tumor that had histologic features of HPV infection. This prompted a longitudinal analysis of HPV DNA in archival material from these urogenital lesions. Colorimetric in situ hybridization was used to assay for HPV types 6, 11, 16, and 18. Human papillomavirus types 6 and 11 were present throughout the period of follow-up in all the condylomatous lesions, including those identified in the bladder, suggesting a common source of infection and spread. By contrast, HPV type 16 was associated only with the vaginal intraepithelial neoplasia that was identified midway through the period of follow-up, and it was apparently cured by excision of the lesion.

Analysis of benign and malignant urogenital tumors for human papillomavirus infection by labelling cellular DNA.

A total of 268 biopsies from the genital region was screened for the presence of human papillomavirus DNA. The specimens included carcinoma of the vulva, vagina, cervix, corpus uteri, ovaries and penis, and Bowen's carcinomas, Bowenoid papuloses, Bowen's disease, cervical intraepithelial neoplasias (CIN I to III), Buschke-Löwenstein tumors, a cervical polyp, decidua, endometrium and histologically normal biopsies. Of 45 carcinomas, 18 contained either HPV 16 and/or 18 and 3 HPV 6-related sequences. In a few individual biopsies double or even triple infections were noted. Unusual was the presence of HPV 2-related DNA in one biopsy from Bowen's disease, whereas 2 condylomata acuminata contained HPV 3-related DNA and one contained HPV DNA related to a group of epidermal HPV's found in epidermodysplasia verruciformis lesions.