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Introduction: The aims of this study were to evaluate urine flow cytometry (UFC) as a tool to screen urine samples of urological patients for bacteriuria and to compare UFC and dipstick analysis with urine culture in a patient cohort at a urological department of a university hospital., Methods and Material: We screened 662 urine samples from urological patients (75.2% male; 80.7% inpatients; mean age 58 years). UFC results were compared to microbiological urine culture., Results: The accuracy in using the UFC-based parameters for detecting cultural bacteriuria was 91.99% and 88.97% for ≥105 colony-forming units (CFU)/mL and ≥104 CFU/mL, respectively. UFC and leukocyte dipstick analysis measured leukocyturia similarly (Pearson correlation coefficient 0.87, p value <0.01%), but dipstick analysis scored less accurately on bacteriuria (accuracy 59.37% and 62.69%). UFC remained effective in subgroup analysis of patients of both sexes and with different urological conditions with its overall use only slightly impaired when assessing gross hematuria (NPV 84.62% for ≥104 CFU/mL). UFC also reliably removed those urine samples below cutoffs with negative predictive values of 99.28% for ≥105 CFU/mL and 95.86% for ≥104 CFU/mL., Conclusion: Counting bacteria with UFC is an accurate and rapid method to determine significant bacteriuria in urological patients and is superior to dipstick analysis or indirect surrogate parameters such as leukocyturia. When UFC is available, we recommend it to be used for the diagnosis of bacteriuria over findings obtained by dipstick analysis., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Novel preventive measures and therapeutic approaches are needed to reduce the frequency of recurrent urinary tract infections (rUTI) and the associated emergence of multidrug-resistant uropathogens. The aim of this review is to systematically present the available evidence on the urinary bladder microbiome of healthy women and those with rUTIs. In addition, relevant studies on the efficacy of probiotics in rUTIs are presented in a structured manner. This will provide an overview on the current state of research and an outlook on treatment strategies beyond the usual antimicrobial options., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Introduction: This exploratory analysis assessed efficacy and safety outcomes in patients with Gram-negative bacteremia treated with ceftazidime-avibactam or comparator across five phase 3, randomized, controlled, multi-center trials in adults with complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI)/pyelonephritis, hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP)., Methods: In each trial, RECLAIM and RECLAIM 3 (cIAI; NCT01499290/NCT01726023), REPRISE (cIAI/cUTI; NCT01644643), RECAPTURE (cUTI; NCT01595438/NCT01599806), and REPROVE (HAP/VAP; NCT01808092), patients were randomized 1:1 to intravenous ceftazidime-avibactam (plus metronidazole for those with cIAI) or comparators (carbapenems in > 97% patients) for 5-21 days. Efficacy assessments included clinical and microbiological responses at the test-of-cure visit in the pooled Gram-negative extended microbiologically evaluable (GNeME) population (bacteremia subset). Safety outcomes were summarized for patients with positive bacterial blood culture(s) at baseline who received ≥ 1 dose of study treatment., Results: The overall safety population included 4050 patients (ceftazidime-avibactam, n = 2024; comparator, n = 2026). The GNeME population (bacteremia subset) comprised 101 patients (ceftazidime-avibactam, n = 54; comparator, n = 47). Clinical cure rates (all indications combined) were 47/54 (87.0%) for ceftazidime-avibactam and 39/47 (83.0%) for comparators; favorable microbiological response rates were 43/54 (79.6%) and 32/47 (68.1%), respectively. Clinical and microbiological responses in the bacteremia subset were generally similar to those in the overall set. The pattern of adverse events in patients with bacteremia was similar between treatment groups and was consistent with the known safety profile of ceftazidime-avibactam., Conclusion: This analysis provides supportive evidence of the efficacy and safety of ceftazidime-avibactam in patients with Gram-negative bacteremia associated with cIAI, cUTI/pyelonephritis, or HAP/VAP., (© 2021. The Author(s).)

Background: Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) is involved in DNA demethylation and transcriptional regulation, plays a key role in the maintenance of stem cell pluripotency, and is dysregulated in malignant cells. The identification of cancer stem cells (CSCs) driving tumor growth and metastasis is the primary objective of biomarker discovery in aggressive prostate cancer (PCa). In this context, we analyzed TET1 expression in PCa., Methods: A large-scale immunohistochemical analysis of TET1 was performed in normal prostate (NOR) and PCa using conventional slides (50 PCa specimens) and tissue microarrays (669 NOR and 1371 PCa tissue cores from 371 PCa specimens). Western blotting, RT-qPCR, and 450 K methylation array analyses were performed on PCa cell lines. Genome-wide correlation, gene regulatory network, and functional genomics studies were performed using publicly available data sources and bioinformatics tools., Results: In NOR, TET1 was exclusively expressed in normal cytokeratin 903 (CK903)-positive basal cells. In PCa, TET1 was frequently detected in alpha-methylacyl-CoA racemase (AMACR)-positive tumor cell clusters and was detectable at all tumor stages and Gleason scores. Pearson's correlation analyses of PCa revealed 626 TET1-coactivated genes (r > 0.5) primarily encoding chromatin remodeling and mitotic factors. Moreover, signaling pathways regulating antiviral processes (62 zinc finger, ZNF, antiviral proteins) and the pluripotency of stem cells were activated. A significant proportion of detected genes exhibited TET1-correlated promoter hypomethylation. There were 161 genes encoding transcription factors (TFs), of which 133 were ZNF-TFs with promoter binding sites in TET1 and in the vast majority of TET1-coactivated genes., Conclusions: TET1-expressing cells are an integral part of PCa and may represent CSCs with oncogenic potential., (© 2021. The Author(s).)

Different perspectives exist among the various specialist disciplines on the treatment of trauma patients with injuries of the urogenital tract. The multidisciplinary consensus guidelines of the World Society of Emergency Surgery (WSES) and the American Association for the Surgery of Trauma (AAST), which appeared in autumn 2019, are summarized in this article. They should constitute an aid to making decisions on the optimal treatment of trauma patients with urogenital injuries., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Alternative treatments for Escherichia coli infections are urgently needed, and phage therapy is a promising option where antibiotics fail, especially for urinary tract infections (UTI). We used wastewater-isolated phages to test their lytic activity against a panel of 47 E. coli strains reflecting the diversity of strains found in UTI, including sequence type 131, 73 and 69. The plaquing host range (PHR) was between 13 and 63%. In contrast, the kinetic host range (KHR), describing the percentage of strains for which growth in suspension was suppressed for 24 h, was between 0% and 19%, substantially lower than the PHR. To improve the phage host range and their efficacy, we bred the phages by mixing and propagating cocktails on a subset of E. coli strains. The bred phages, which we termed evolution-squared ε 2 -phages, of a mixture of Myoviridae have KHRs up to 23% broader compared to their ancestors. Furthermore, using constant phage concentrations, Myoviridae ε 2 -phages suppressed the growth of higher bacterial inocula than their ancestors did. Thus, the ε 2 -phages were more virulent compared to their ancestors. Analysis of the genetic sequences of the ε 2 -phages with the broadest host range reveals that they are mosaic intercrossings of 2-3 ancestor phages. The recombination sites are distributed over the whole length of the genome. All ε 2 -phages are devoid of genes conferring lysogeny, antibiotic resistance, or virulence. Overall, this study shows that ε 2 -phages are remarkably more suitable than the wild-type phages for phage therapy.

Introduction: The COVID (coronavirus disease 2019) pandemic has shown impressively that infectious diseases can have an enormous impact on the healthcare system and beyond. In the specialty of urology, patients present in daily practice with viral infections that are associated with numerous diseases., Methodology: The aim of this review is to describe viral infections relevant for urology, and in particular to emphasize vaccination prevention. A selective literature search was carried out on the subjects of "COVID and urology", "urogenital viral infections", "viral urological infections in transplant medicine", and "vaccination prevention of viral diseases"., Results: Coronaviruses have already caused two local epidemics: SARS (severe acute respiratory syndrome) epidemic and MERS (Middle East respiratory syndrome) epidemic. The fact that the SARS-CoV‑2 (SARS coronavirus 2) disease is contagious even without symptoms has essentially led to the rapid spread and global pandemic. A large number of viruses, which can also induce viremia, have been detected in the ejaculate and are thus associated with a possible urogenital infection. These include the mumps virus, Coxsackie viruses or enteroviruses, among others. It has also been shown that a Zika virus infection can also be sexually transmitted via the sperm as a carrier. Viruses therefore also play an important role in reproduction. When performing kidney transplants, urologists are often confronted with viral infections. The most effective weapon against viruses is prevention by vaccination., Conclusion: In terms of ethiopathogenesis, the genitourinary tract is most often affected by viruses, in the context of viremia or through reactivation due to immunosuppression. Immunomodulation and vaccination prophylaxis play a leading role in therapy., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background:  In sight of increasing bacterial resistances, appropriate and cautious antibiotic therapy (antibiotic stewardship) is becoming more and more important, in private practices as well. A current S3 guideline is available for the treatment of uncomplicated urinary tract infections, which recommends that regular epidemiological examinations of pathogen sensitivity are to be carried out promptly and locally. With this said, the antibiotic prescriptions of the resident doctors in Hesse were examined and compared with the sensitivity of the most important pathogens causing urinary tract infections., Material and Method:  The prescription data for antibiotics (ATC J01) for the area of ​​the Association of Statutory Health Insurance Physicians in Hessen for the years 2013 to 2020 were received from Insight Health GmbH & Co. KG, Waldems-Esch, which manages the data. A large laboratory that supplies numerous resident doctors in the Rhine-Main region provided sensitivity data tested according to CLSI until the year 2016 and from 2017 to EUCAST from microbiological examinations of urine samples for the clarification of community-acquired urinary tract infections from the years 2011-2020., Results:  From 2013 to 2020 the antibiotic prescriptions decreased from 2 692 370 to 1 708 134 (minus 37 %). The prescriptions for cephalosporins were reduced by more than 40 %, those of quinolones by 76 %. Among the antibiotics recommended for urinary tract infections, the most common antibiotics used were fosfomycin (2020: 130 476), followed by co-trimoxazole (2020: 96 559), nitrofurantoin (2020: 37 415), trimethoprim (2020: 27 388), pivmecillinam (20 984) and nitroxoline (6818). Urologists, on the other hand, most frequently prescribed nitrofurantoin (2020: 9951) and co-trimoxazole (9772), followed by fosfomycin (7193), trimethoprim (5050), nitroxoline (3289) and pivmecillinam (2722). Despite the high use of fosfomycin in outpatient medicine, E. coli and Citrobacter spp. exhibited no loss of sensitivity, Proteus mirabilis and S. aureus showed a slight loss of activity, while in Enterobacter cloacae a clear loss of activity was seen. The E. coli strains detected from urine samples to clarify complicated urinary tract infections show continuously excellent sensitivity for fosfomycin, nitrofurantoin, nitroxoline and mecillinam (> > 90 %), whereas the sensitivity against trimethoprim was just under 80 %., Discussion and Conclusion:  The decrease in antibiotic prescription data from statutory health insurance physicians in Hesse shows that the importance of cautious antibiotic therapy is also gaining ground in outpatient practice. Co-trimoxazole, which continues to be used very frequently, should be avoided in favor of monotherapy with trimethoprim because of the increased side effects of the sulfonamide component with the same effectiveness of trimethoprim. The E. coli strains detected from urine samples to clarify complicated urinary tract infections showed a sensitivity, of just under 80 % to trimethoprim. Since an approximately 10 % better sensitivity rate was found for uncomplicated community-acquired urinary tract infections that usually do not require microbiological diagnostics, in our opinion, in transferring this observation in the Rhine-Main area and in Hesse, trimethoprim can also continue to be used empirically for uncomplicated urinary tract infections., Competing Interests: UH und MW haben keine Interessenkonflikte. FW gibt Studienunterstützung durch Deutsche Forschungsgemeinschaft (DFG), Deutsches Zentrum für Infektionsforschung (DZIF), sowie Studienunterstützung und/oder Vorträge durch Achaogen, Astellas, AstraZeneca, Bionorica, Cubist/MSD, Eumedica, GSK, Janssen, Klosterfrau, Leo-Pharma, Marpinion, Medpace, Merlion, Paratek, Pfizer, OM/Vifor Pharma, Rempex, Rosen Pharma, VenatoRx an., (Thieme. All rights reserved.)

Competing Interests: F. Wagenlehner: Deutsche Forschungsgemeinschaft (DFG), Deutsches Zentrum für Infektionsforschung (DZIF), Achaogen, Astellas, AstraZeneca, Bionorica, Cubist/MSD, Eumedica, GSK, Janssen, Klosterfrau, Marpinion, Medpace, Merlion, Paratek, Pfizer, OM/ Vifor Pharma, Rempex, Rosen Pharma, VenatoRx.T. Speck: Der Autor gibt an, dass kein Interessenkonflikt besteht.

Infectious complications following prostate biopsy are on the rise due to an increase in antimicrobial resistance, mainly against fluoroquinolones. The use of fluoroquinolones for perioperative prophylaxis is no longer approved by the national authorities in Germany. The EAU guideline group on urological infections has recently published a meta-analysis in two parts based on randomised controlled trials (RCTs). Transperineal prostate biopsy is associated with a significantly reduced rate of infectious complications compared with transrectal biopsy and should therefore be preferred. If transrectal biopsy is performed, intrarectal cleaning with povidone-iodine and antibiotic prophylaxis without fluoroquinolones should be chosen. Antibiotic prophylactic strategies include targeted prophylaxis after susceptibility testing of the rectal flora, augmented prophylaxis with multiple antibiotics and empiric mono-prophylaxis with non-fluoroquinolones. Data from RCTs are available for aminoglycosides, third-generation cephalosporins and fosfomycin trometamol., Competing Interests: FW gibt Studienunterstützung durch Deutsche Forschungsgemeinschaft (DFG), Deutsches Zentrum für Infektionsforschung (DZIF), sowie Studienunterstützung und/oder Vorträge durch Achaogen, Astellas, AstraZeneca, Bionorica, Cubist/MSD, Eumedica, GSK, Janssen, Klosterfrau, Leo-Pharma, Marpinion, Medpace, Merlion, Paratek, Pfizer, OM/Vifor Pharma, Rempex, Rosen Pharma, VenatoRx an., (Thieme. All rights reserved.)

Background: Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a frequent disease affecting men of every age and accounting for a great number of consultations at urology departments. Previous studies suggested a negative impact of CP/CPPS on fertility. As increasing attention has been attributed to additional aspects, such as sperm DNA integrity and sperm protein alterations, besides the WHO standard semen analysis when assessing male fertility, in this prospective study, we aimed to further characterize the fertility status in CP/CPPS patients with a focus on these parameters., Methods: Sperm DNA fragmentation measured by sperm chromatin structure assay (SCSA) and protamine 1 to protamine 2 mRNA ratio assessed by RT-qPCR were analyzed along with conventional ejaculate parameters and inflammatory markers in 41 CP/CPPS patients and 22 healthy volunteers., Results: We found significant differences between the groups concerning multiple conventional ejaculate parameters. A significant increase in sperm DNA fragmentation was shown in CP/CPPS patients with association to other sperm parameters. The majority of CP/CPPS patients exhibited protamine mRNA ratios out of the range of regular fertility., Conclusions: This is a pioneering study with a strong practical orientation revealing that CP/CPPS leads to increased sperm DNA damage and changes in sperm protamine levels, emphasizing an unfavorable impact of CP/CPPS on fertility.

Objective: The goal of the present study was to evaluate treatment with Canephron ® compared to standard antibiotic treatment after diagnosis of acute cystitis or urinary tract infection (UTI), with regard to the risk of sporadic recurrent UTIs, frequent recurrent UTIs, UTI-related sick leave, additional antibiotic prescriptions, and renal complications (pyelonephritis). Methods: This retrospective cohort study was based on data from the IMS ® Disease Analyzer database (IQVIA), and included outpatients in Germany with at least one diagnosis of acute cystitis or UTI with a prescription of either Canephron ® or standard antibiotics between January 2016 and June 2019 and treated in general practitioner (GP), gynecologist, or urologist practices, from which the data were obtained. Multivariable regression models were used to investigate the association between Canephron ® prescription and the amount of sporadic or frequent recurrent UTIs, as well as the duration of UTI-related sick leave, the number of additional antibiotic prescriptions, and cases of pyelonephritis. The effects of Canephron ® were adjusted for age, sex, insurance status, and Charlson comorbidity score (CCI). Results: 2320 Canephron ® patients and 158,592 antibiotic patients were available for analysis. Compared to antibiotic prescription, Canephron ® prescription was significantly associated with fewer sporadic recurrences of UTI infections 30-365 days after the index date (odds ratio (OR): 0.66; 95%, confidence interval (CI): 0.58-0.72), as well as less frequent recurrences of UTI infections (OR: 0.61; 95% CI: 0.49-0.88), and also with reduced additional antibiotic prescription within 31-365 days (OR: 0.57; 95% CI: 0.52-0.63). No significant differences were observed between the Canephron ® and antibiotic cohorts with regard to the likelihood of sick leave (OR: 0.99; 95% CI: 0.86-1.14), new antibiotic prescription within 1-30 days (OR: 1.01; 95% CI: 0.87-1.16), or occurrence of pyelonephritis (Hazard Ratio (HR): 1.00; 95% CI: 0.67-1.48). Conclusion: These real-world data show that Canephron ® is an effective, safe symptomatic treatment for acute cystitis or UTI. It should be considered as an alternative treatment, particularly to also strengthen antimicrobial stewardship strategies.

Urinary tract infections are among the most common bacterial infections. A significant proportion of urinary tract infections recur, which leads to impairments in patients' physical intimacy, social contacts and ability to work. The standardised ACSS questionnaire can provide help in establishing a diagnosis and assessing the course of the disease. In addition to general education and counselling on risk factors for urinary tract infections, non-antibiotic treatment options are particularly important for reducing recurrence. This aims to prevent the development of resistance to antibiotics and their undesirable side-effects. Non-antibiotic strategies most notably include personal counselling with communication of behavioural recommendations, immunoprophylaxis, phytotherapeutics and local oestrogen substitution. However, in cases of high patient suffering, antibiotic prophylaxis should also be considered after due deliberation. In summary, individual counselling should take place and treatment should be given in a multimodal therapeutic approach., Competing Interests: D. Faßl: Der Autor gibt an, dass kein Interessenkonflikt besteht; F. Wagenlehner: Reports grants from Deutsches Zentrum für Infektionsforschung (DZIF), personal fees and other from Achaogen, personal fees from AstraZeneca, personal fees and other from Bionorica, other from Enteris BioPharma, other from Helperby Therapeutics, personal fees from Janssen, personal fees from LeoPharma, personal fees from MerLion, personal fees from MSD, personal fees and other from OM Pharma/Vifor Pharma, personal fees from Pfizer, personal fees from RosenPharma, personal fees and other from Shionogi, personal fees from VenatoRx, personal fees from GSK, personal fees and other from Klosterfrau GmbH, personal fees from Eumedica, outside the submitted work., (Thieme. All rights reserved.)

Objective: Coronavirus disease-19 (COVID-19) pandemic caused delays in definitive treatment of patients with prostate cancer. Beyond the immediate delay a backlog for future patients is expected. The objective of this work is to develop guidance on criteria for prioritisation of surgery and reconfiguring management pathways for patients with non-metastatic prostate cancer who opt for surgical treatment. A second aim was to identify the infection prevention and control (IPC) measures to achieve a low likelihood of coronavirus disease 2019 (COVID-19) hazard if radical prostatectomy (RP) was to be carried out during the outbreak and whilst the disease is endemic., Methods: We conducted an accelerated consensus process and systematic review of the evidence on COVID-19 and reviewed international guidance on prostate cancer. These were presented to an international prostate cancer expert panel (n = 34) through an online meeting. The consensus process underwent three rounds of survey in total. Additions to the second- and third-round surveys were formulated based on the answers and comments from the previous rounds. The Consensus opinion was defined as ≥80% agreement and this was used to reconfigure the prostate cancer pathways., Results: Evidence on the delayed management of patients with prostate cancer is scarce. There was 100% agreement that prostate cancer pathways should be reconfigured and measures developed to prevent nosocomial COVID-19 for patients treated surgically. Consensus was reached on prioritisation criteria of patients for surgery and management pathways for those who have delayed treatment. IPC measures to achieve a low likelihood of nosocomial COVID-19 were coined as 'COVID-19 cold' sites., Conclusion: Reconfiguring management pathways for patients with prostate cancer is recommended if significant delay (>3-6 months) in surgical management is unavoidable. The mapped pathways provide guidance for such patients. The IPC processes proposed provide a framework for providing RP within an environment with low COVID-19 risk during the outbreak or when the disease remains endemic. The broader concepts could be adapted to other indications beyond prostate cancer surgery., (© 2020 The Authors BJU International © 2020 BJU International.)

Purpose: We identify which nonantibiotic strategies could reduce the risk of infectious complications following prostate biopsy., Materials and Methods: We performed a literature search on MEDLINE®, Embase® and the Cochrane Database for randomized controlled trials (inception to May 2020) assessing nonantibiotic interventions in prostate biopsy. Primary outcome was pooled infectious complications (fever, sepsis and symptomatic urinary tract infection) and secondary outcome was hospitalization. Cochrane risk of bias tool and GRADE approach were used to assess the bias and the certainty of evidence. The study protocol was registered with PROSPERO (CRD42015026354)., Results: A total of 90 randomized controlled trials (16,941 participants) were included in the analysis, with 83 trials being categorized into one of 10 different interventions. Transperineal biopsy was associated with significantly reduced infectious complications as compared to transrectal biopsy (RR 0.55, 95% CI 0.33-0.92, p=0.02, I 2 =0%, 1,330 participants, 7 studies). Rectal preparation with povidone-iodine was also shown to reduce infectious complications (RR 0.50, 95% CI 0.38-0.65, p <0.000001, I 2 =27%, 1,686 participants, 8 studies) as well as hospitalization (RR 0.38, 95% CI 0.21-0.69, p=0.002, I 2 =0%, 620 participants, 4 studies). We found no difference in infectious complications/hospitalization for 6 other interventions, ie number of biopsy cores, periprostatic nerve block, number of injections for periprostatic nerve block, needle guide type, needle type and rectal preparation with enema. In 2 interventions (needle diameter, rectal preparation with chlorhexidine) meta-analysis was not possible. Finally, 7 studies had unique interventions. The certainty of evidence was rated as low/very low for all interventions., Conclusions: Transperineal biopsy significantly reduces infectious complications compared to transrectal biopsy and should therefore be preferred. If transrectal biopsy is performed, rectal preparation with povidone-iodine is highly recommended. The other investigated nonantibiotic strategies did not significantly influence infection and hospitalization after prostate biopsy.

Objectives: To develop an international consensus on managing penile cancer patients during the COVID-19 acute waves. A major concern for patients with penile cancer during the coronavirus disease 2019 (COVID-19) pandemic is how the enforced safety measures will affect their disease management. Delays in diagnosis and treatment initiation may have an impact on the extent of the primary lesion as well as the cancer-specific survival because of the development and progression of inguinal lymph node metastases., Materials and Methods: A review of the COVID-19 literature was conducted in conjunction with analysis of current international guidelines on the management of penile cancer. Results were presented to an international panel of experts on penile cancer and infection control by a virtual accelerated Delphi process using 4 survey rounds. Consensus opinion was defined as an agreement of ≥80%, which was used to reconfigure management pathways for penile cancer., Results: Limited evidence is available for delaying penile cancer management. The consensus rate of agreement was 100% that penile cancer pathways should be reconfigured, and measures should be developed to prevent perioperative nosocomial transmission of COVID-19. The panel also reached a consensus on several statements aimed at reconfiguring the management of penile cancer patients during the COVID-19 pandemic., Conclusions: The international consensus panel proposed a framework for the diagnostic and invasive therapeutic procedures for penile cancer within a low-risk environment for COVID-19., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: Extraintestinal pathogenic Escherichia coli (ExPEC) are a leading cause of invasive infections in adults. The study aimed to evaluate the incidence of microbiologically confirmed invasive ExPEC disease in patients undergoing transrectal ultrasound-guided prostate needle biopsy (TRUS-PNB), O-serotype distribution and antibiotic resistance profiles of associated E. coli isolates., Materials and Methods: Adult men (≥18 years) undergoing TRUS-PNB were enrolled. The TRUS-PNB procedure was performed according to local standard of care, including preferences of prophylactic antibiotics. Clinical and microbiological data were collected., Results: Of the 4,951 patients (mean age 66.9 years) enrolled 4,935 (99.7%) underwent TRUS-PNB (95.1% received prophylactic antibiotics); 98.9% completed the study. Overall incidence of invasive ExPEC disease was 0.67% (33/4,935 patients; 95% CI 0.46-0.94); highest incidence was in the U.S. (0.97%, 14/1,446; 95% CI 0.53-1.62). Prevalence of the 10 selected O-serotypes O1, O2, O4, O6, O8, O15, O16, O18, O25 and O75 was 52.0% (95% CI 31.3-72.2). E. coli isolates showed highest resistance rates to levofloxacin and ciprofloxacin (76%; 95% CI 54.8-90.6 for both). Among fluoroquinolone-resistant ExPEC isolates, prevalence of the 10 selected O-serotypes was 60%., Conclusions: This study provides an estimate of microbiologically confirmed invasive ExPEC disease incidence following TRUS-PNB. Information on E. coli O-serotype distribution and associated antibiotic resistance profiles from invasive ExPEC disease cases in the first 30 days following TRUS-PNB may help guiding antibiotic use and inform development of a prophylactic ExPEC vaccine.

Background: Sexual health is becoming increasingly important for many HIV-positive men undergoing highly effective antiretroviral therapy (ART) but remains frequently unaddressed in routine clinical consultation., Aim: To comprehensively evaluate sexual health in male patients with HIV on stable ART over a 12-month period., Methods: The prospectively registered cohort study comprising 87 HIV-positive men on stable ART (median age: 43 years) was conducted between 2011 and 2015 at a university hospital. Patients were enrolled from the outpatient infectious disease unit and underwent an extensive andrological workup to assess parameters of sexual health (questionnaires, sex hormones, ultrasound, 2-glass urine test including semen analysis with microbiological and viral diagnostics). The study period per patient lasted 12 months., Outcome: The primary endpoint was the impact of chronic HIV infection on sexual health., Results: Although, on average, sexual health was fine at baseline, 56% of the patients reported erectile dysfunction, 28% experienced reduced libido, 5% had hypogonadism, 36% showed at least 1 atrophic testicle with a volume of <10 ml, 8% suffered bacterial sexually transmitted infections, 35% had seminal inflammation, and up to 47% showed reduced sperm quality. Sexual satisfaction was linked to mental health (12-Item Short Form Health Survey questionnaire) and International Index of Erectile Function scores. During the study period, the collected parameters on sexual health were generally stable. However, 35% of patients had new sex partners (median: 5 partners), 7% had fathered a child or were planning procreation, 47% reported changed libido, 17% suffered bacterial sexually transmitted infections in the urogenital tract, 16% revealed a positive HIV viral load in blood, 11% had a positive HIV viral load in semen, and 28% were treated for andrological disorders., Clinical Implications: Sexual ill-health exists in about one third of patients. This manifests itself in sexual dysfunction, sexually transmitted infections, urogenital tract inflammation, and abnormal sperm parameters, all of which require adequate counseling and therapy., Strength and Limitations: The strength of this study is its comprehensive analysis of male sexual health over a 12-month period of stable ART treatment. Limitations are a heterogeneous patient cohort and a rather small percentage of patients with a positive HIV viral load in blood or semen, which prevented multivariate risk analysis., Conclusion: Our study provides evidence that sexual health should be actively taken into account in the routine consultation by infectious disease specialists, and an interdisciplinary approach is desirable in the case of symptoms or signs of sexual ill-health. Pilatz A, Maresch CC, Discher T, et al. Sexual Health in HIV-Positive Men Under Stable Antiretroviral Therapy During a 12-Month Period. J Sex Med 2021;18:284-294., (Copyright © 2020 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Nephrotoxicity and neurotoxicity are commonly associated with polymyxin treatment; however, the emergence of multidrug-resistant Gram-negative bacteria with limited therapeutic options has resulted in increased use of polymyxins., Objectives: To determine the rates of nephrotoxicity and neurotoxicity during polymyxin treatment and whether any factors influence these., Data Sources: Medline, Embase and Cochrane Library databases were searched on 2 January 2020., Study Eligibility Criteria: Studies reporting nephrotoxicity and/or neurotoxicity rates in patients with infections treated with polymyxins were included. Reviews, meta-analyses and reports not in English were excluded., Participants: Patients hospitalized with infections treated with systemic or inhaled polymyxins were included. For comparative analyses, patients treated with non-polymyxin-based regimens were also included., Methods: Meta-analyses were performed using a random-effects model; subgroup meta-analyses were conducted where data permitted using a mixed-effects model., Results: In total, 237 reports of randomized controlled trials, cohort and case-control studies were eligible for inclusion; most were single-arm observational studies. Nephrotoxic events in 35,569 patients receiving polymyxins were analysed. Overall nephrotoxicity rate was 0.282 (95% confidence interval (CI) 0.259-0.307). When excluding studies where >50% of patients received inhaled-only polymyxin treatment or nephrotoxicity assessment was by methods other than internationally recognized criteria (RIFLE, KDIGO or AKIN), the nephrotoxicity rate was 0.391 (95% CI 0.364-0.419). The odds of nephrotoxicity were greater with polymyxin therapies compared to non-polymyxin-based regimens (odds ratio 2.23 (95% CI 1.58-3.15); p < 0.001). Meta-analyses showed a significant effect of polymyxin type, dose, patient age, number of concomitant nephrotoxins and use of diuretics, glycopeptides or vasopressors on the rate of nephrotoxicity. Polymyxin therapies were not associated with a significantly different rate of neurotoxicity than non-polymyxin-based regimens (p 0.051). The overall rate of neurotoxicity during polymyxin therapy was 0.030 (95% CI 0.020-0.043)., Conclusions: Polymyxins are associated with a higher risk of nephrotoxicity than non-polymyxin-based regimens., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Mobile phone applications (apps) for urinary tract infections (UTIs) can help in the management of UTIs., Objective: To review the apps available for UTIs and check its adherence to the European Association of Urology (EAU) guidelines., Design, Setting, and Participants: We reviewed all mobile phone apps from the iTunes App Store and Google Play for UTIs and evaluated various aspects of apps, as well as their current and potential usage in screening, prevention, or management. The inclusion criteria were English-language apps for adults with upper or lower tract UTIs., Outcome Measurements and Statistical Analysis: Each app was sorted into one of the following categories: "informative", "tracker", or "urinalysis"; each app was then checked for its adherence to EAU guidelines based on a 31-point checklist. One point was given for each piece of specific advice provided by the app, with a maximum score of 31., Results and Limitations: A total of 34 apps were initially identified from the app download platforms, and after exclusions, 11 were evaluated. The apps had a high average user rating of 4.04 (range: 0-5). The median number of downloads was 1000 (range: <100-100 000). The average adherence to the EAU checklist was low at 31.36% (3.3-70%). The app performance for prevention of recurrent UTIs, uncomplicated cystitis, and pyelonephritis was 14.9%, 33.1%, and 41.4%, respectively., Conclusions: Apps to support the management of UTIs could be improved by better adherence to European guidelines and recommendations based on up-to-date evidence, especially for the management of recurrent UTIs., Patient Summary: In this study, we look at the role of mobile phone applications (apps) in screening, prevention, and management of urinary tract infections and their adherence to European Association of Urology guidelines. We found that apps need to improve with better compliance to European guidelines, especially for the management of recurrent urinary tract infections., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Infectious complications following prostate biopsy are increasing and fluoroquinolone prophylaxis has recently been suspended in Germany by the national authorities., Objectives: This review is intended to highlight current strategies for reducing infectious complications following prostate biopsy., Materials and Methods: The European Association of Urology (EAU) guideline group on urological infections recently published a meta-analysis in two parts based on randomized controlled trials (RCTs). The most important contents shall be presented here., Results: Transperineal prostate biopsy is associated with significantly reduced infectious complications than transrectal biopsy. If transrectal biopsy is performed, intrarectal cleaning with povidone-iodine and antibiotic prophylaxis without fluoroquinolones should be chosen. Antibiotic prophylactic strategies include targeted prophylaxis after susceptibility testing of the rectal flora, augmented prophylaxis with multiple antibiotics and empiric monoprophylaxis with nonfluoroquinolones. Here data from RCTs are available for aminoglycosides, third generation cephalosporines, and fosfomycin trometamol., Conclusions: The transperineal approach is preferred to reduce prostate biopsy-related infections. Fluoroquinolones are no longer approved for prophylaxis. Thus, alternative antibiotics based on local resistance, or targeted prophylaxis, in conjunction with povidone-iodine rectal preparation are recommended for transrectal prostate biopsy.

Circulating tumor cells (CTCs) are considered to be promising biomarkers in malignant diseases. Recently, molecular profiles of CTCs in prostate cancer (PCa) and the role of CTCs in neoadjuvant chemotherapy and transurethral resections of bladder cancer (BCa) are intensely studied. However, localized PCa and nonmuscle-invasive BCa are less investigated and discussed. Moreover, the benefit and feasibility of clinical applications of CTCs should be critically questioned and reevaluated. This review focuses mainly on clinical issues and lesser on methodologies, and summarizes the quintessence of available works dealing with clinical applications of CTCs in PCa and BCa management., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Uncomplicated urinary tract infection (UTI) in women is a common reason to present in general practice and is usually treated with antibiotics to reduce symptom severity and duration. Results of recent clinical trials indicate that non-antibiotic treatment approaches can also be effective. However, it remains unclear which patients would benefit from antibiotic treatment and which can effectively and safely be treated without antibiotics. This systematic review and meta-analysis aims to estimate the effect of treatment strategies to reduce antibiotic use in comparison with immediate antibiotic treatment and to identify prognostic factors and moderators of treatment effects. A further aim is to identify subgroups of patients benefiting from a specific therapy., Methods and Analysis: A systematic literature search will be performed to identify randomised controlled trials which investigated the effect of treatment strategies to reduce antibiotic use in female adults with uncomplicated UTI compared with immediate antibiotic treatment. Therefore, the primary outcome of the meta-analysis is incomplete recovery. Anonymised individual patient data (IPD) will be collected. Aggregate data will be used for pairwise comparisons of treatment strategies using meta-analysis models with random effects accounting for potential between-study heterogeneity. Potential effect moderators will be explored in meta-regressions. For IPD, generalised linear mixed models will be used, which may be adjusted for baseline characteristics. Interactions of baseline variables with treatment effects will be explored. These models will be used to assess direct comparisons of treatment, but might be extended to networks., Ethics and Dissemination: The local institutional review and ethics board judged the project a secondary analysis of existing anonymous data which meet the criteria for waiver of ethics review. Dissemination of the results will be via published scientific papers and presentations. Key messages will be promoted for example, via social media or press releases., Prospero Registration Number: CRD42019125804., Competing Interests: Competing interests: IG, GF, TF, EH, MM are involved in the following studies: ‘REGATTA—reducing antibiotic use for uncomplicated urinary tract infection in general practice by treatment with uva-ursi’. Afshar K, Fleischmann N, Schmiemann G, Bleidorn J, Hummers-Pradier E, Friede T, Wegscheider K, Moore M, Gagyor I. 'Reducing antibiotic use for uncomplicated urinary tract infection in general practice by treatment with uva-ursi (REGATTA)—a double-blind, randomised, controlled comparative effectiveness trial'. BMC Complement Altern Med. 2018 Jul 3;18(1):203. doi: 10.1186/s12906-018-2266-x). IV was involved in the study: ‘Vik I, Bollestad M, Grude N, Bærheim A, Damsgaard E, Neumark T, Bjerrum L, Cordoba G, Olsen IC, Lindbæk M. Ibuprofen versus pivmecillinam for uncomplicated urinary tract infection in women—a double-blind, randomised non-inferiority trial'. PLoS Med 15;5:e1002569. Doi.org/10.1371/journal.pmed.1002569. MM, ADH and PL are coauthors of the study: ‘Moore M, Trill J, Simpson C, Webley F, Radford M, Stanton L, Maishman T, Glanopoulou A, Flower A, Eyles C, Willcox M, Hay AD, van der Werf E, Gibbons S, Lewith G, Little P, Griffiths G. Uva-ursi extract and ibuprofen as alternative treatments for uncomplicated urinary tract infection in women (ATAFUTI): a factorial randomised trial. Clinical Microbiology and Infection'. Doi.org/10.1016/j.cmi.2019.01.011. SH was involved in the study with the reference number 11. PL and MM were involved in the study with the reference number 12. SF and TM were involved in the study with the reference number 13. IG, EH were involved in the studies with the reference numbers 14 and 15. AK was involved in the study with the reference number 16., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The reassessment of known but neglected natural compounds is a vital strategy for providing novel lead structures urgently needed to overcome antimicrobial resistance. Scaffolds with resistance-breaking properties represent the most promising candidates for a successful translation into future therapeutics. Our study focuses on chelocardin, a member of the atypical tetracyclines, and its bioengineered derivative amidochelocardin, both showing broad-spectrum antibacterial activity within the ESKAPE ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa , and Enterobacter species) panel. Further lead development of chelocardins requires extensive biological and chemical profiling to achieve favorable pharmaceutical properties and efficacy. This study shows that both molecules possess resistance-breaking properties enabling the escape from most common tetracycline resistance mechanisms. Further, we show that these compounds are potent candidates for treatment of urinary tract infections due to their in vitro activity against a large panel of multidrug-resistant uropathogenic clinical isolates. In addition, the mechanism of resistance to natural chelocardin was identified as relying on efflux processes, both in the chelocardin producer Amycolatopsis sulphurea and in the pathogen Klebsiella pneumoniae. Resistance development in Klebsiella led primarily to mutations in ramR , causing increased expression of the acrAB-tolC efflux pump. Most importantly, amidochelocardin overcomes this resistance mechanism, revealing not only the improved activity profile but also superior resistance-breaking properties of this novel antibacterial compound.

Purpose: To study the effector mechanism against pathogens of polymorphonuclear neutrophils (PMN) and macrophages, called ETosis, involving the release of extracellular traps (ETs) in patients with acute epididymitis. To assess the different ET phenotypes present in semen samples and to identify correlations between ETosis and clinical parameters., Materials and Methods: Samples from patients diagnosed with acute epididymitis were examined and compared with samples from uninfected controls. Biochemical analyses of seminal fluid included determination of peroxidase, α-glucosidase, fructose, and elastase levels. ETosis in semen was determined through presence of citrullinated histones, global histones, and extracellular DNA. Different ETosis phenotypes such as spread ETs, aggregated ETs, and diffuse ETs were identified by co-localisation of extruded DNA with myeloperoxidase and global histones. Anti-CD15 + and anti-CD68 + antibodies were used to identify different cell lines., Results: Revealed a high number of ETs compared with the control group. The mean number of CD15 + PMN and CD68 + macrophages was higher in the acute epididymitis group. ETosis increase in ejaculates correlated with clinical parameters such as enhancement of elastase concentrations and diminution of fructose in the semen., Conclusions: This work shows for the first time the presence of ETs and their components in semen from patients with acute epididymitis. The presence of infections is an important factor for induction of ETs in semen. Furthermore, the presence of ETosis in ejaculates is suggestive of developing infectious processes and might possibly have a diagnostic value.

Clinical practice guidelines have become increasingly important in the decision-making process in many clinical conditions and have been recognized as key instruments to improve the quality of care. On the one hand, guidelines represent a good tool for improving patient's outcome, and on the other hand, the adherence to guidelines and good practice recommendations is mandatory to reduce the risk of legal disputes. A recent revision by the Italian Parliament of the legal system that rules the responsibilities of health professionals and health care safety stimulated all clinicians to improve their adhesion to clinical guidelines. It is justified by the high-quality level obtained in the recent years by the international guidelines. In the recent years, a revision of the clinical guideline development has been done. In particular, the European Association of Urology Guideline Office changed the "Guidelines for Guidelines," and a rigorous development process has been established. A clinical recommendation is produced after a rigorous methodological process using an analysis of all published clinical trials, and the expert opinion is not yet considered. For oncological guidelines, the adherence to the producing process is easily feasible due to the high number of clinical trials; for non-oncological guidelines, instead, the small number of clinical trials could represent a problem for obtaining recommendation based on rigorous methodology. Here, on the basis of these considerations, we aim to discuss the lights and the shadows of the clinical applicability of guidelines in urology.

Purpose: Infectious complications following prostate biopsy are increasing and fluoroquinolone prophylaxis has recently been banned by the European Commission. In this systematic review we summarize the evidence for different antibiotic prophylaxis regimens., Materials and Methods: We searched MEDLINE®, Embase® and Cochrane Database for randomized controlled trials (inception to October 2019) assessing antimicrobial interventions in prostate biopsy. Primary outcome was infectious complications. Exclusion criteria were simultaneous interfering interventions. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) was used to assess the certainty of evidence. Protocol was registered with PROSPERO (CRD42015026354)., Results: Overall 59 randomized controlled trials (14,153 participants) and 7 different antimicrobial interventions were included. Antibiotic prophylaxis reduced infectious complications compared to no prophylaxis (RR 0.56, 95% CI 0.40-0.77, p=0.0005, I 2 =15%, participants 1,753, studies 11). A short-term prophylaxis (single shot to 3 days) was inferior to a long-term prophylaxis (1 to 7 days) with fluoroquinolone (RR 1.89, 95% CI 1.37-2.61, p=0.0001, I 2 =0%, participants 3,999, studies 17). Fosfomycin trometamol was an alternative to fluoroquinolone with reduced rates of infectious complications (RR 0.49, 95 CI 0.27-0.87, p=0.02, I 2 =54%, participants 1,239, studies 3). Empiric prophylaxis was inferior to targeted prophylaxis (RR 1.81, 95% CI 1.28-2.55, p=0.0008, I 2 =48%, participants 1,511, studies 6). Standard prophylaxis was inferior to augmented prophylaxis (using multiple rather than single agent) using a fixed model (RR 2.10, 95% CI 1.53-2.88, p <0.0001, I 2 =71%, participants 2,597, studies 9), but not using a random model (p=0.07). No difference was observed in infectious complications based on route or timing of antimicrobial prophylaxis. The certainty of evidence was rated as low/very low., Conclusions: In countries where fluoroquinolones are allowed as antibiotic prophylaxis, a minimum of a full 1-day administration as well as targeted therapy in case of fluoroquinolone resistance is recommended. In countries with a ban on fluoroquinolones, fosfomycin is a good alternative, as is augmented prophylaxis, although no established standard combination exists to date.

Given the increasing antimicrobial resistance in urinary tract infections (UTI), alternative strategies need to be investigated. Determination of minimal inhibitory and bactericidal concentrations of essential oils from cajeput, lemongrass, tea tree, and thyme in artificial urine, revealed bactericidal activity of all four tested essential oils against seven uropathogenic species with values ranging between 0.78-50 mg/mL. Tea tree and thyme essential oils were more efficient than lemongrass and cajeput. In addition, antibiotic-resistant strains showed similar susceptibility as antibiotic-sensitive strains, suggesting no cross-resistance between antibiotics and these essential oils. Checkerboard assays revealed a synergistic activity of the combination of thyme and tea tree. Furthermore, the combination with thyme and tea tree essential oils increased the activity of fosfomycin and pivmecillinam, but not nitrofurantoin, against Escherichia coli . This study provides a basis for further investigation of the potential of thyme and tea tree oil as an alternative or additional treatment of UTI.

This is the eighth chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2 nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience. The chapter deals with the treatment of more severe infections of the kidney and the urogenital tract, including urosepsis. Recommendations for empiric and targeted antibacterial treatment are given., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Fünfstück et al.)

Background: Urinary tract infections are among the more common types of nosocomial infection in Germany and are associated with catheters in more than 60% of cases. With increasing rates of antibiotic resistance worldwide, it is essential to distinguish catheter-associated asymptomatic bacteriuria from catheter-associated urinary tract infection (CA-UTI)., Methods: This review is based on publications from January 2000 to March 2019 that were retrieved by a selective search in Medline. Randomized clinical trials and systematic reviews in which the occurrence of CA-UTI in adult patients was a primary or secondary endpoint were included in the analysis. Two authors of this review, working independently, selected the publications and extracted the data., Results: 508 studies were identified and 69 publications were selected for analysis by the prospectively defined criteria. The studies that were included dealt with the following topics: need for catheterization, duration of catheterization, type of catheter, infection prophylaxis, education programs, and multiple interventions. The duration of catheterization is a determinative risk factor for CA-UTI. The indications for catheterization should be carefully considered in each case, and the catheter should be left in place for the shortest possible time. The available data on antibiotic prophylaxis do not permit any definitive conclusion, but they do show a small benefit from antibiotic-impregnated catheters and from systemic antibiotic prophylaxis., Conclusion: Various measures, including careful consideration of the indication for catheterization, leaving catheters in place for the shortest possible time, and the training of nursing personnel, can effectively lower the incidence of CA-UTI. The eous in some respects, and thus no recommendations can be given on certain questions relevant to CA-UTI.

Background: Health care-associated urinary tract infection (HAUTI) consists of unique conditions (cystitis, pyelonephritis and urosepsis). These conditions could have different pathogen diversity and antibiotic resistance impacting on the empirical antibiotic choices. The aim of this study is to compare the estimated chances of coverage of empirical antibiotics between conditions (cystitis, pyelonephritis and urosepsis) in urology departments from Europe., Methods: A mathematical modelling based on antibiotic susceptibility data from a point prevalence study was carried. Data were obtained for HAUTI patients from multiple urology departments in Europe from 2006 to 2017. The primary outcome of the study is the Bayesian weighted incidence syndromic antibiogram (WISCA) and Bayesian factor. Bayesian WISCA is the estimated chance of an antibiotic to cover the causative pathogens when used for first-line empirical treatment. Bayesian factor is used to compare if HAUTI conditions did or did not impact on empirical antibiotic choices., Results: Bayesian WISCA of antibiotics in European urology departments from 2006 to 2017 ranged between 0.07 (cystitis, 2006, Amoxicillin) to 0.89 (pyelonephritis, 2009, Imipenem). Bayesian WISCA estimates were lowest in urosepsis. Clinical infective conditions had an impact on the Bayesian WISCA estimates (Bayesian factor > 3 in 81% of studied antibiotics). The main limitation of the study is the lack of local data., Conclusions: Our estimates illustrate that antibiotic choices can be different between HAUTI conditions. Findings can improve empirical antibiotic selection towards a personalized approach but should be validated in local surveillance studies.

Introduction: The genomic revolution has transformed our understanding of urinary tract infection. There has been a paradigm shift from the dogmatic statement that urine is sterile in healthy people, as we are becoming forever more familiar with the knowledge that bacterial communities exist within the urinary tracts of healthy people. Metagenomics can investigate the broad populations of microbial communities, analysing all the DNA present within a sample, providing comprehensive data regarding the state of the microenvironment of a patient's urinary tract. This permits medical practitioners to more accurately target organisms that may be responsible for disease-a form of 'precision medicine'., Methods and Results: This paper is derived from an extensive review and analysis of the available literature on the topic of metagenomic sequencing in urological science, using the PubMed search engine. The search yielded a total of 406 results, and manual selection of appropriate papers was subsequently performed. Only one randomised clinical trial comparing metagenomic sequencing to standard culture and sensitivity in the arena of urinary tract infection was found., Conclusion: Out of this process, this paper explores the limitations of traditional methods of culture and sensitivity and delves into the recent studies involving new high-throughput genomic technologies in urological basic and clinical research, demonstrating the advances made in the urinary microbiome in its entire spectrum of pathogens and the first attempts of clinical implementation in several areas of urology. Finally, this paper discusses the challenges that must be overcome for such technology to become widely used in clinical practice.

Purpose: Urinary tract infections are amongst the most frequent nosocomial infections followed by surgical site infections (SSI). Antibiotic prophylaxis is only one way to reduce the risk of post-operative infection. Our aim was to establish a review of the literature on measures to reduce post-operative infections outside antibiotic prophylaxis., Methods: We performed a review of the literature in February 2019 using Medline database to identify relevant studies published in the last 10 years. We arbitrarily decided to fix our limit to the 10 last years considering that the resistance rate of bacteria to antibiotics and the surgical technics evolve over time. This search identified 229 studies. We included 53 studies selected upon the title or the abstract., Results: Forty-four studies were finally included. We evaluated the efficacy to prevent SSI by skin antisepsis, surgical hand hygiene and technique, type of surgeons' caps, preservation of normothermia, hair removal, increased oxygen delivery, wound protectors, bathing, normoglycemia and immunonutrition., Conclusions: Antibiotic prophylaxis represents one way to prevent SSI but various other measures should be known and considered by anesthesiologists and surgeons. Some measures to reduce post-operative infections are not clearly established yet and more studies are needed.

Considering infection/inflammation to be an important risk factor in male infertility, the aim of this study was to make a comprehensive evaluation of the prevalence of urogenital tract infection/inflammation and its potential impact on sperm retrieval in azoospermic patients. In this prospective study, 71 patients with azoospermia were subjected to an extensive andrological workup including comprehensive microbiological diagnostics (2-glass test, semen, testicular swab and testicular tissue analysis) and testicular biopsy/testicular sperm extraction (TESE). Medical history suggested urogenital tract infection/inflammation in 7% of patients, 11% harboured STIs, 14% showed significant bacteriospermia, 15% had seminal inflammation, 17% fulfilled the MAGI definition, and 27% had relevant pathogens. At the testicular level, 1 patient had a swab positive for bacteria, no viruses were detected, tissue specimens never indicated pathogens, whereas histopathology revealed focal immune cell infiltrates in 23% of samples. Testicular sperm retrieval rate was 100% in obstructive and 46% in nonobstructive azoospermia. None of the infection/inflammation-related variables was associated with the success of sperm retrieval or inflammatory lesions in the testis. The high prevalence of urogenital infection/inflammation among azoospermic men underpins their role as significant aetiologic factors in male infertility. However, this observation does not refer to the chances of sperm retrieval at the time of surgery/TESE., (© 2019 The Authors. Andrologia published by Blackwell Verlag GmbH.)

Ceftazidime/avibactam (CAZ-AVI) is a novel, fixed-dose combination antibiotic that has been approved in Europe and the United States for patients with complicated urinary tract infections (cUTIs) based on results of a Phase III, randomized, comparative study (RECAPTURE study). The present analysis evaluated cost-effectiveness of CAZ-AVI as an empirical treatment for hospitalized patients with cUTIs from the Italian publicly funded healthcare (third-party payer) perspective. A sequential, patient-level simulation model was developed that followed the clinical course of cUTI and generated 5000 pairs of identical patients (CAZ-AVI or imipenem as empirical treatment). The model included additional impact of resistant pathogens; patients who did not respond to empirical treatment were switched to second-line treatment of colistin+high dose carbapenem in both groups. The time horizon of the model was five years, with an annual discount rate of 3% applied to both costs and quality-adjusted life-years (QALYs). The analysis demonstrated that an intervention sequence (CAZ-AVI followed by colistin+high dose carbapenem) compared with a comparator sequence (imipenem followed by colistin+high dose carbapenem) was associated with a net incremental cost of €1015 per patient but provided better health outcomes in terms of clinical cure (97.65% vs. 91.08%; ∆ = 6.57%), shorter hospital stays (10.65 vs. 12.55 days; ∆ = 1.90 days), and QALYs gained per patient (4.190 vs. 4.063; ∆ = 0.126). The incremental cost-effectiveness ratio was €8039/QALY, which is well below the willingness-to-pay threshold of €30 000/QALY in Italy. The results showed that CAZ-AVI is expected to be a cost-effective treatment compared with imipenem for cUTI in Italy., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

In the context of refugee migrations infectious diseases are being more frequently diagnosed, which the responsible physicians as well as urologists have never seen before. This is due to the poorer health and hygiene conditions in the country of origin, during the flight and in the refugee camps. In Europe increasing incidences of tuberculosis, schistosomiasis and scabies have recently been observed. Tuberculosis and schistosomiasis are often accompanied by unspecific symptoms or can resemble normally encountered urological diseases. Due to the highly contagious nature of scabies, a screening of new arrivals is recommended. A timely differential diagnostic inclusion of these disease patterns is enormously important. Despite the reduction in the numbers of asylum applications in Germany, a higher number of unregistered migrants is generally assumed, who also elude the healthcare system and can therefore contribute to the spread of these rare infectious diseases.

Leucocytospermia has been associated with loss of sperm function. Extracellular traps (ETs) of leucocytes are produced during innate immune response. ETs can be activated by spermatozoa in contact with polymorphonuclear (in vitro), inducing sperm entrapment and decrease motility. In this pilot study, we describe the results of ETosis ex vivo, in seminal fluid (SF) smear of infertile patients, associating ETs with leucocytospermia and bacteriospermia. In 21 infertile patients, semen parameters (WHO, 2010), microbiological study, leucocytospermia and presence of ETs in SF were determined. Leucocytes (CD45, CD15 and CD68) were evaluated by immunostaining in SF smears. Indirect immunofluorescence (global histone and H4-citrullinated 3) and scanning electron microscopy (SEM) were used to determine ETs morphology. In 28.6% of patients presented leucocytospermia without bacteriospermia, all of them presented a large number of ETs in the SF smears examined. About 76.6% of the patients without leucocytospermia were positive for ETs. Samples with leucocytospermia have a higher number of ETs and would be related to the amount of leucocytes in the SF. The morphological predominant ETs were diffuse (diffETs) and spread (sprETs). The formation of ETs indicates leucocyte activation in semen, and it was observed that ETosis does not depend exclusively on the presence of bacterial contamination., (© 2019 Blackwell Verlag GmbH.)

The presence of bacteria and/or leukocytes can alter semen quality resulting in low sperm quality and infertility. Inflammation or infection increases the numbers of PMN or macrophages/monocytes in male genital tract. Release of extracellular traps (ETs) by leukocytes has been recognized as a novel mechanism of early host innate immunity, in response to invasive pathogens. This is the first work that evaluated the mechanism of triggered ETs in monocytes co-incubated with spermatozoa or bacteria and the effect on sperm function. Selected spermatozoa and human monocytes isolated from peripheral blood were obtained by healthy donors. Two experimental models were developed, one aseptic (non-infectious) incubating spermatozoa and monocytes, and septic models (infectious) incubating spermatozoa with monocytes and uropathogenic Escherichia coli ( E. coli ). ETs of monocytes (METs) (DNA, global histone and citrullinated histones) were visualized by scanning electron microscopy (SEM) and immunofluorescence analyses. Progressive motility was performed at 0, 10, 30, 60, and 180 min after co-incubation with CASA system. SEM- and immunofluorescence-analyses revealed human spermatozoa alone or in the presence of E. coli as strong inducers METs. In aseptic model, the motility decreased to 65.2 ± 3.5% at 10 min of incubation and 29.3 ± 3.3% at 30 min (p < 0.001). In septic model, motility decreased to 44.5 ± 5.9% (10 min) and 12.7 ± 2.2% (30 min) (p < 0.001). MET-derived small spermatozoa aggregations were observed in both models. METs might physically block spermatozoa and decrease motility after a brief contact. This may impair male fertility, especially in patients with genital tract infections or chronic inflammation. Abbreviations : PMN: polymorphonuclear; ETs: extracellular traps; E. coli: Escherichia coli ; METs: ETs of monocytes; SEM: scanning electron microscopy; NE: neutrophil elastase; MPO: myeloperoxidase; MAGI: male accessory gland infection; PBMC: peripheral blood mononuclear cells; RT: room temperature; CFU: colony forming units; CASA: computer-aided sperm analysis; H4Cit3: histone H4 citrullinated 3.

Orchitis can be acutely symptomatic or chronically asymptomatic. Among the acute forms is the rarer isolated orchitis, which is of viral origin in most cases as well as the more frequent secondary orchitis, which is usually the result of an ascending bacterial epididymitis. In addition, sterile forms of orchitis are also seen in patients with systemic autoimmune comorbidities. Chronic asymptomatic orchitis is the term used to describe cellular immune infiltrates in the testes, which are observed in approximately 25% of cases of azoospermia during testicular biopsy. The etiopathogenesis of these infiltrates is largely unknown with postinfection and primary pathogen-independent autoimmune reactions being discussed. Animal experimental models of orchitis may be helpful to investigate the immunological mechanisms involved as well as the therapeutic possibilities.

Background: Health care associated urinary tract infections (HAUTI) is a common complicating factor of urological practice. It is unclear what the appropriate empirical antibiotic choices are and how infection control policies (ICP) influence this. The aim of this study is to use probabilistic approaches towards the problem. That is to determine the chances of coverage of empirical antibiotic choices in HAUTIs and their annual trends in Europe. In addition, the impact of departmental self-reported compliance with catheter management and regulated usage of prophylactic antibiotics policies was tested. The estimated chances of coverage of antibiotics and further probabilistic calculations are carried out using the Global Prevalence of Infections in Urology (GPIU) annual surveillance study European data., Methods: GPIU is a multi-state annual prevalence study conducted in urology departments to detect patients with HAUTIs, using the Center for Disease Control (CDC) definitions and antimicrobial resistance (AMR). In this analysis; the European cohort from 2005 to 2015 was used. The estimated chance of coverage for each antibiotic choice in HAUTIs was calculated using the Bayesian Weighted Incidence Syndromic Antibiogram (WISCA) approach. Annual trend of the overall cohort and number of appropriate antibiotic choices were estimated. Departments were compared according to their self-reported compliance to ICPs to determine if there was an impact on chances of coverage and appropriate antibiotic choices., Results: We estimated that in most study years less than half of the single agent antibiotics and all combination options were appropriate for empirical treatment of HAUTIs. Departments with compliance to both ICPs were estimated to have 66%(2006) to 44% (2015) more antibiotic choices compared to departments with complete lack of compliance to the ICPs. In our estimates departments with adherence to a single policy was not superior to departments with complete lack of adherence to ICPs., Conclusions: Most single agent choices had limited coverage for HAUTIs and combination choices had improved chance of coverage. Optimal antibiotic selection decision should be part of decision experiments and tested in local surveillance studies. Departments with self-reported compliance to ICPs have more antibiotic choices and details of the compliance should be evaluated in future studies. The analysis herein showed that over the 10-year course there was no clear time trend in the chances of coverage of antibiotics (Bayesian WISCA) in European urology departments., Competing Interests: The authors have declared that no competing interests exist.