Validation of the Spanish Acute Cystitis Symptoms Score (ACSS) in native Spanish-speaking women of Europe and Latin America.

INTRODUCTION AND OBJECTIVES: The Acute Cystitis Symptom Score (ACSS) is a patient self-reporting questionnaire for clinical diagnostics and patient-reported outcome (PRO), which may assess the symptoms and the effect on the quality of life in women with acute cystitis (AC). The current study aimed to create a validated Spanish version of the ACSS questionnaire. MATERIAL AND METHODS: The process of linguistic validation of the Spanish version of the ACSS consisted of the independent forward and backward translations, revision and reconciliation, and cognitive assessment. Clinical evaluation of the study version of the ACSS was carried out in clinics in Spain and Latin America. Statistical tests included the calculation of Cronbach's α, split-half reliability, specificity, sensitivity, diagnostic odds ratio, positive and negative likelihood ratio, and area under the receiver-operating characteristic curve (AUC). RESULTS: The study was performed on 132 patients [age (mean;SD) 45.0;17.8 years] with AC and 55 controls (44.5;12.2 years). Cronbach's α of the ACSS was 0.86, and the split-half reliability was 0.82. The summary scores of the ACSS domains were significantly higher in patients than in controls, 16.0 and 2.0 (p < 0.001), respectively. The predefined cut-off point of ≥6 for a summary score of the "Typical" domain resulted in a specificity of 83.6% and a sensitivity of 99.2% for the Spanish version of the ACSS. AUC was 0.91 [0.85; 0.97]. CONCLUSIONS: The validated Spanish ACSS questionnaire evaluates the symptoms and clinical outcomes of patients with AC. It can be used as a patient's self-diagnosis of AC, as a PRO measure tool, and help to rule out other pathologies in patients with voiding syndrome.

Phytotherapy (BNO 1045) of Acute Lower Uncomplicated Urinary Tract Infection in Women Normalizes Local Host Responses.

INTRODUCTION: Acute lower uncomplicated urinary tract infection (uUTI) affects a large proportion of women. Increased antimicrobial resistance has created an urgent need for novel therapeutics and the phytotherapeutic drug BNO 1045 (Canephron® N) has previously been shown to be noninferior to standard antimicrobial stewardship. This sub-analysis from a randomized, double-blind, controlled phase III noninferiority clinical trial using BNO 1045 versus fosfomycin to treat uUTI aimed to determine how urine cytokine levels are altered by the two different treatments. METHODS: Urine samples from a predefined subset of women diagnosed with uUTI (18-70 years) and treated with BNO 1045 (n = 58) or fosfomycin (n = 69) were analyzed for urine levels of IL-6 and IL-8, using analyte-to-creatinine ratios. RESULTS: BNO 1045 treatment showed similar effects to fosfomycin treatment in reducing both urine IL-6 and IL-8 levels. Mean IL-6 and IL-8 levels were markedly reduced in all patients regardless of treatment. BNO 1045 treatment decreased urine IL-8 significantly (p = 0.0142) and showed a trend toward reduction of urine IL-6 (p = 0.0551). Fosfomycin treatment reduced both IL-6 and IL-8 levels significantly (p = 0.0038, <0.0001 respectively). CONCLUSION: BNO 1045 is, in addition to reducing symptoms, comparable to fosfomycin treatment in reducing the local inflammatory response associated with uUTI.

Linguistic and Clinical Validation of the Tajik Acute Cystitis Symptom Score for Diagnosis and Patient-Reported Outcome in Acute Uncomplicated Cystitis.

Background and Objectives: Acute Cystitis Symptom Score (ACSS) is a self-reporting questionnaire for clinical diagnosis and follow-up of acute uncomplicated cystitis (AC) in women. The ACSS, originally developed in Uzbek and Russian, both considered original languages, is now available in several other languages. This study aimed to translate and validate the ACSS in the Tajik language. Material and Methods: Linguistic validation was carried out according to the Linguistic Validation Manual for Patient-Reported Outcomes Instruments guidelines. Clinical validation was performed by enrolling fifty-four Tajik-speaking women. All women included in this study were first interviewed about the understandability of all questions and statements in the final Tajik ACSS and were asked to fill in form A at the first visit (diagnostics) and form B at any follow-up visit (patient-reported outcome). Results: Thirty-three women, median (range) age of 35 (18-77), were diagnosed with AC (patient group), while twenty-one women, median (range) age of 34 (20-61) (p = 0.109), were enrolled as the control group without any other urological disease. For the diagnostics of AC, a summary score of the six typical symptoms ("Typical" domain) showed the best balance between sensitivity (0.73) and specificity (0.71) at 5 and above. Cronbach's alpha [95% CI] and split-half reliability [95%] were 0.82 [0.76; 0.98] and 0.84 [0.77; 0.87], respectively. At the follow-up visit, the patients reported a significant reduction in the "Typical" domain and an improvement in the "Quality of Life" domain. Conclusion: The Tajik ACSS showed good reliability and diagnostic values and may be used as a reliable tool for the diagnosis and patient-reported outcome in women with AC in clinical and epidemiological studies and for daily practice.

The negative aftermath of prostate biopsy: prophylaxis, complications and antimicrobial stewardship: results of the global prevalence study of infections in urology 2010-2019.

PURPOSE: To evaluate and report the complications, and to analyse antimicrobial stewardship aspects following prostate biopsies (P-Bx) based on the data from a 9-year global study. METHODS: The primary outcome was to compare complications after P-Bx between patients of two cohorts: 2010-2014 and 2016-2019. Primary outcomes included symptoms of lower and severe/systemic urinary tract infection (LUTIS and SUTIS, respectively), and positive urine culture. Readmission to hospital after P-Bx, need for additional antimicrobial therapy, consumption of different antimicrobial agents for prophylaxis and therapy were evaluated. Students t test and chi-square test were used for comparative analyses. RESULTS: Outcome data were available for 1615 men. Fluoroquinolones-based prophylaxis rate increased from 72.0% in 2010-2014 to 78.6% in 2015-2019. Overall rates of complications increased from 6 to 11.7% including an increase in symptomatic complications from 4.7 to 10.2%, mainly due to an increase in LUTIS. Rates of patients seeking additional medical help in primary care after P-Bx increased from 7.4 to 14.4%; cases requiring post P-Bx antibiotic treatment increased from 6.1 to 9.7%, most of which received fluoroquinolones. Transperineal P-Bx was significantly associated with LUTIS. Following transrectal P-Bx, 2.8% developed febrile infections and 4.0% required hospitalisation. Two men (0.12%) died after transrectal P-Bx due to sepsis. CONCLUSIONS: The rates of complications after P-Bx tended to increase in time, as well as rates of patients seeking additional medical help in the post-P-Bx period. To reduce the risk of infectious complications and to comply with the principles of antibiotic stewardship, clinicians should switch to the transperineal biopsy route.

Linguistic and clinical validation of the acute cystitis symptom score in German-speaking Swiss women with acute cystitis.

INTRODUCTION AND HYPOTHESIS: The Global Prevalence Study of Infections in Urinary tract in Community Setting (GPIU.COM) includes epidemiological aspects of acute cystitis (AC) in women in Germany and Switzerland. The primary study relates to the German version of the Acute Cystitis Symptom Score (ACSS), a self-reporting questionnaire for self-diagnosis and monitoring the symptomatic course of AC in women. The current study aimed to analyze the validity and reliability of the German ACSS in German-speaking female patients with AC in Switzerland. METHODS: Anonymized patient data were collected and analyzed from women with AC at the first visit (diagnosis) and follow-up visits as baseline and controls, respectively. Data from 97 patients with a median age of 41 years underwent analysis. Psychometric and diagnostic characteristics of the ACSS were measured and statistically analyzed. RESULTS: Average internal consistency of the ACSS resulted in a Cronbach's alpha (95% CI) of 0.86 (0.83; 0.89) and did not differ significantly between the Swiss and German cohorts. Diagnostic values of the ACSS for the Swiss cohort were relatively lower than for the German cohort, possible due to discrepancies between definitions of UTI in national guidelines. CONCLUSIONS: The analysis showed that the German version of the ACSS is also suitable for use in the German-speaking female population of Switzerland. Minor differences in definitions of AC between German and Swiss guidelines explain the observed discrepancies in diagnostic values of the ACSS between cohorts.

Changes in the management of urinary tract infections in women: impact of the new recommendations on antibiotic prescribing behavior in France, between 2014 and 2019.

BACKGROUND: Urinary tract infections (UTIs) are among the most common infections that require antibiotic therapy. In December 2015, new guidelines for UTI management were published in France with the aim of reducing antibiotic misuse and the risk of antimicrobial resistance. OBJECTIVES: To analyze changes in antibiotic prescribing behavior for acute uncomplicated UTI in women in France from 2014 to 2019. METHODS: Retrospective study using data extracted from the medico-administrative database 'OpenMedic' that is linked to the French National Health Data System and collects data on the reimbursement of prescribed drugs. The analyses focused on the number of boxes of antibiotics delivered by community pharmacies, the molecule class, and the prescriber's specialty. RESULTS: Overall, antibiotic dispensing by community pharmacies increased by 2% between 2014 and 2019, but with differences in function of the antibiotic class. The use of antibiotics recommended as first-line and second-line treatment increased (+ 41% for fosfomycin and + 7430% for pivmecillinam). Conversely, the dispensing of lomefloxacin and norfloxacin decreased by 80%, and that of ciprofloxacin by 26%. Some antibiotics were mostly prescribed by general practitioners (lomefloxacin, pivmecillinam) and others by secondary care physicians (ofloxacin). Dispensing increased for antibiotics prescribed by secondary care physicians (+ 13% between 2014 and 2019) and decreased for antibiotics prescribed by GPs (- 2% for the same period). CONCLUSION: These data suggest that the new recommendations are followed, as indicated by the increased prescription of fosfomycin and pivmecillinam and decreased prescription of fluoroquinolones. However, the efficient transmission and implementation of new recommendations by practitioners requires time, means and dedicated tools.

Anti-Biofilm Effect of Octenidine and Polyhexanide on Uropathogenic Biofilm-Producing Bacteria.

BACKGROUND: A catheter allowing a release of antibacterial substances such as antiseptics into the bladder could be a new way of preventing biofilm formation and subsequent catheter-associated urinary tract infections. METHODS: Minimal inhibitory and bactericidal concentration (MIC/MBC) determinations in cation-adjusted Mueller-Hinton broth and artificial urine were performed for 4 antiseptics against 3 uropathogenic biofilm producers, Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis. Furthermore, effects of octenidine and polyhexanide against catheter biofilm formation were determined by quantification of biofilm-producing bacteria. RESULTS: Sodium hypochlorite showed MIC/MBC values between 200 and 800 mg/L for all strains tested. Triclosan was efficient against E. coli and P. mirabilis (MIC ≤2.98 mg/L) but ineffective against P. aeruginosa. Octenidine and polyhexanide showed antibacterial activity against all 3 species tested (MIC 1.95-7.8 and 3.9-31.25 mg/L). Both octenidine and polyhexanide were able to prevent biofilm formation on catheter segments in a concentration dependent manner. Furthermore, adding 250 mg/L of each biocide disrupted biofilms formed by E. coli and P. mirabilis, whereas even 500 mg/L was not sufficient to completely destroy P. aeruginosa biofilms. CONCLUSION: Octenidine- and polyhexanide-containing antiseptics showed a broad effect against typical uropathogenic biofilm producers even in high dilutions. This study provides a basis for further investigation of the potential of octenidine and polyhexanide as prophylaxis or treatment of catheter biofilms.

Metagenomics in diagnosis and improved targeted treatment of UTI.

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.

Condition-specific surveillance in health care-associated urinary tract infections as a strategy to improve empirical antibiotic treatment: an epidemiological modelling study.

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.

Evaluation of the draft guidelines proposed by EMA and FDA for the clinical diagnosis of acute uncomplicated cystitis in women.

PURPOSE: To reassess the diagnostic values of the "draft" guidelines for the clinical diagnosis of acute uncomplicated cystitis (AC), recently proposed by US Food and Drug Administration (FDA) and European Medicines Agency (EMA). METHODS: The data of 517 female respondents (patients with acute cystitis and controls) derived from the e-USQOLAT database were analyzed and used for the validation of proposed "draft" guidelines of FDA and EMA, compared to the Acute Cystitis Symptom Score (ACSS) questionnaire. The diagnostic values of the proposals concerning signs, symptoms and their severity were assessed and compared. RESULTS: The six "typical" symptoms of the ACSS were strongly associated with the diagnosis of AC. The number of positive "typical" symptoms differed significantly between patients and controls: median 5 (IQR 4-6) vs 1 (IQR 0-3) respectively. Scored severity of "typical" symptoms also differed significantly between groups of patients and controls: median (IQR) 10 (7-13) vs 1 (0-4), respectively. The best balance between sensitivity and specificity is shown by the ACSS cut-off value of 6 scores and more of the "Typical" domain, followed by an approach proposed by FDA and EMA, justifying ACSS to be used as a diagnostic criterion for the clinical diagnosis of AC. CONCLUSIONS: Not only the presence but also the severity of the symptoms is important for an accurate diagnosis of AC. The ACSS, even without urinalysis is at least as favourable as the draft diagnostic proposals by FDA and EMA. The ACSS can be recommended for epidemiological and interventional studies, and allows women to establish self-diagnosis of AC, making the ACSS also cost-effective for healthcare.

Carbapenem-Containing Combination Antibiotic Therapy against Carbapenem-Resistant Uropathogenic Enterobacteriaceae.

The increasing global prevalence of carbapenem-resistant Enterobacteriaceae (CRE) combined with the decline in effective therapies is a public health care crisis. After respiratory tract infections, urinary tract infections and associated urosepsis are the second most affected by CRE pathogens. By using checkerboard analysis, we tested eight different antibiotics in combination with carbapenems in CAMHB (cation-adjusted Müller-Hinton broth) and artificial urine against seven CRE strains and three susceptible strains. To further determine whether these combinations are also effective in a dynamic model, we have performed growth curves analyses in a dynamic bladder model with three uropathogenic CRE strains. In this model, we simulated the urinary pharmacokinetic after application of 1,000 mg intravenous (i.v.) ertapenem alone or in combination with 500 mg i.v. levofloxacin, 1,000 mg oral rifampin, or 3,000 mg oral fosfomycin. Bacterial growth was measured for 48 h, simulating voiding of the bladder every 3 h. According to the median fractional inhibitory concentration indices (ΣFICIs), the values we found were additive to synergistic results across all tested CRE strains for combinations of carbapenems with colistin sulfate, levofloxacin, fosfomycin, rifampin, and tigecycline in CAMHB and artificial urine. In the dynamic bladder model, all three CRE strains tested showed regrowth after treatment with ertapenem up to 48 h. Regrowth could be prevented by combination with levofloxacin, fosfomycin, or rifampin. Carbapenem-containing combination therapy with fosfomycin or rifampin could be an option for better treatment of urinary tract infections (UTIs) caused by CRE strains. This should be further investigated in clinical studies.

Reliability of Symptom-Based Diagnosis of Uncomplicated Cystitis.

BACKGROUND AND OBJECTIVES: Acute uncomplicated cystitis (AC) is common among women. Acute onset of specific typical symptoms may serve as reliable criteria for developing a cost-effective strategy to make an accurate diagnosis of AC. We aimed to evaluate the diagnostic values of most common symptoms and signs of AC depending on their presence and severity. METHODS: The current trial was designed as a case-control study. Data derived from the Acute Cystitis Symptom Score (ACSS) database were analyzed. Diagnostic values of the symptoms and their severity were assessed via the calculations of the sensitivity and specificity, odds ratio, positive and negative likelihood ratios. The strength of associations was estimated by the coefficient of correlation (Pearson's R). RESULTS: Data from 819 female subjects (423 Patients, 396 controls) with the mean age of 37.1 ± 15.3 were analyzed. Highest diagnostic values for AC in this study belonged to dysuria, urgency, and frequency. Interestingly, complaints of vaginal discharge was not found to decrease the odds for having AC in the study population. CONCLUSIONS: The severity of the symptom is even more essential than just its presence for an accurate diagnosis. The ACSS is an accurate tool and may be recommended for clinical practice and studies for diagnosis of AC in women. Further studies and unification of terms are need.

Prevention and treatment of uncomplicated lower urinary tract infections in the era of increasing antimicrobial resistance-non-antibiotic approaches: a systemic review.

PURPOSE: Urinary tract infections (UTIs) are one of the more common infections encountered in everyday clinical practice. They account for 10-20% of all infections treated in primary care units and 30-40% of those treated in hospitals. The risk of UTI in the female population is considered to be 14 times higher than in the male population. The prevalence of bacterial etiology results in a large consumption of broad-spectrum antibiotics, which in turn leads to increased rates of resistant uropathogens. Therefore, non-antibiotic prevention and treatment options are now of great importance. METHODS: A systematic literature search was performed for the last 20 years (1999-2019) and the efficiencies of these eight different non-antibiotic interventions were analysed and discussed. RESULTS: This article provides an overview on non-antibiotic options for management of UTI, including the application of cranberry products, the phytodrug Canephron N, probiotics, nonsteroidal anti-inflammatory drugs (NSAID), D-mannose, estrogens, vitamins, and immunotherapy. CONCLUSIONS: The last 20 years of research on non-antibiotic approaches in UTI have not brought conclusive evidence that antibiotic usage can be replaced completely by non-antibiotic options. Hence, antibiotics still remain a gold standard for UTI treatment and prevention. However, changing the therapeutic strategy by including non-antibiotic measures in the management of UTI could be successful in avoiding antimicrobial resistance at least to some extent.

Multidisciplinary approach to prostatitis.

The modern clinical research on prostatitis started with the work of Stamey and coworkers who developed the basic principles we are still using. They established the segmented culture technique for localizing the infections in the males to the urethra, the bladder, or the prostate and to differentiate the main categories of prostatitis. Such categories with slight modifications are still used according to the NIH classification: acute bacterial prostatitis, chronic bacterial prostatitis, Chronic Pelvic Pain Syndrome (CPPS) and asymptomatic prostatitis. Prostatic inflammation is considered an important factor in influencing both prostatic growth and progression of symptoms of benign prostatic hyperplasia and prostatitis. Chronic inflammation/neuroinflammation is a result of a deregulated acute phase response of the innate immune system affecting surrounding neural tissue at molecular, structural and functional levels. Clinical observations suggest that chronic inflammation correlates with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH) and an history of clinical chronic prostatitis significantly increases the odds for prostate cancer. The NIHNIDDK classification based on the use of the microbiological 4- glasses localization test or simplified 2-glasses test, is currently accepted worldwide. The UPOINT system identifies groups of clinicians with homogeneous clinical presentation and is used to recognize phenotypes to be submitted to specific treatments. The UPOINTS algorithm implemented the original UPOINT adding to the urinary domains (U), psycho-social (P), organspecific (O), infection (I), neurological (N), muscle tension and tenderness (T) a further domain related to sexuality (S). In fact sexual dysfunction (erectile, ejaculatory, libido loss) has been described in 46-92% of cases with a high impact on the quality of life of patients with CP/CPPS. Prostatic ultrasound represents the most popular imaging test in the work-up of either acute and chronic prostatitis although no specific hypo-hyperechoic pattern has been clearly associated with chronic bacterial prostatitis and CPPS. Use of a digital-processing software to calculate the extension of prostatic calcification area at ultrasound demonstrated a higher percentage of prostatic calcification in patients with chronic bacterial prostatitis. Multiparametric Magnetic Resonance Imaging (mpMRI) is the current state-of-the art imaging modality in the assessment of patients with prostate cancer although a variety of benign conditions, including inflammation, may mimic prostate cancer and act as confounding factors in the discrimination between neoplastic and non-neoplastic lesions. Bacteria can infect prostate gland by: ascending the urethra, reflux of urine into the prostatic ducts, direct inoculation of bacteria through inserted biopsy needles or hematogenous seeding. Enterobacteriaceae are the predominant pathogens in acute and chronic bacterial prostatitis, but an increasing role of Enterococci has been reported. Many strains of these uropathogens exhibit the ability to form biofilm and multidrug- resistance. Sexually Transmitted Infections (STI) agents, in particular Chlamydia trachomatis and Mycoplasma genitalium, have been also considered as causative pathogens of chronic bacterial prostatitis. On the contrary the effective role in genital diseases of other "genital mycoplasmas" is still a much debated issue. Sexually Transmitted Infections agents should be investigated by molecular methods in both patient and sexual partner. "Next generation" investigations, such as cytokine analysis, cytological typing of immune cells could help stratifying the immune response. Epigenetic dysregulation of inflammatory factors should be investigated according to systemic and compartment-specific signals. The search for biomarkers should also include evaluation of hormonal pathways, as measurement of estrogen levels in semen. Antimicrobials are the first line agents for the treatment of bacterial prostatitis. The success of antimicrobial treatment depends on the antibacterial activity and the pharmacokinetic characteristics of the drug which must reach high concentrations in prostate secretion and prostate tissue. Acute bacterial prostatitis can be a serious infection with a potential risk for urosepsis For iInitial treatment of severely ill patients, intravenous administration of high doses of bactericidal antimicrobials, such as broad-spectrum penicillins, third-generation cephalosporins or fluoroquinolones, is recommended in combination with an aminoglycoside. Use of piperacillin-tazobactam and meropenem is justified in presence of multiresistant gramnegative pathogens. The antibiotic treatment of chronic prostatitis is currently based on the use of fluoroquinolones that, given for 2 to 4 weeks, cured about 70% of men with chronic bacterial prostatitis. For the treatment of Chlamydial prostatitis macrolides were shown to be more effective than fluoroquinolones, whereas no differences were observed in microbiological and clinical efficacy between macrolides and tetracyclines for the treatment of infections caused by intracellular pathogens. Aminoglycosides and fosfomycin could be considered as a therapeutic alternative for the treatment of quinolone resistant prostatitis. Use of alpha-blockers in CP/CPPS patients with urinary symptoms and analgesics +/- non steroidal anti-inflammatory drugs (NSAID), in presence of pain demonstrated a reduction of symptoms reduction and an improvement of quality of life, although long term use of NSAID is limited by side effect profile. However, the multimodal therapeutic regimen by contemporary use of alphablockers, antibiotics and anti-inflammatory showed a better control of prostatitis symptoms than single drug treatment. Novel therapeutic substances for the treatment of pain, such as the cannabinoid anandamide would be highly interesting to test. An alternative for the treatment of chronic prostatitis/chronic pelvic pain syndrome is phytotherapy, as primary therapy or in association with other drugs. Quercetin, pollen extract, extract of Serenoa repens and other mixtures of herbal extracts showed a positive effect on symptoms and quality of life without side effects. The association of CP/CPPS with alterations of intestinal function has been described. Diet has its effects on inflammation by regulation of the composition of intestinal flora and direct action on the intestinal cells (sterile inflammation). Intestinal bacteria (microbiota) interacts with food influencing the metabolic, immune and inflammatory response of the organism. The intestinal microbiota has protective function against pathogenic bacteria, metabolic function by synthesis of vitamins, decomposition of bile acids and production of trophic factors (butyrate), and modulation of the intestinal immune system. The alteration of the microbiota is called "dysbiosis" causing invasive intestinal diseases pathologies (leaky gut syndrome and food intolerances, irritable bowel syndrome or chronic inflammatory bowel diseases) and correlating with numerous systemic diseases including acute and chronic prostatitis. Administration of live probiotics bacteria can be used to regulate the balance if intestinal flora. Sessions of hydrocolontherapy can represent an integration to this therapeutic approach. Finally, microbiological examination of sexual partners can offer supplementary information for treatment.

Comparison of fosfomycin against fluoroquinolones for transrectal prostate biopsy prophylaxis: an individual patient-data meta-analysis.

PURPOSE: To systematically review and meta-analyse available evidence comparing fosfomycin trometamol (FT) to fluoroquinolone (FQ) prophylaxis to prevent transrectal ultrasound-guided prostate biopsy (TRUSPB) related infectious complications. METHODS: Electronic databases were queried for studies comparing FT to FQ-based TRUSPB prophylaxis. Studies were assessed for comparable outcomes and methodological quality (ROBINS-I modification). The primary outcome measure was the relative odds of overall infectious complications following TRUSPB according to FT/FQ treatment, which was evaluated with meta-analysis. Safety and tolerability were also assessed. The relative odds of infections of different severity [Grade 1, bacteriuria and afebrile urinary tract infection (UTI); Grade 2, bacteraemia, febrile UTI, and urosepsis] according to FT/FQ treatment were also estimated. RESULTS: Five studies, being three prospective randomised trials and two retrospective cohort studies, representing 3112 patients, were included. The relative odds of an infectious complication (OR 0.22, 95% CI 0.09-0.54) or of a more severe (Grade 2) infection (OR 0.13, 95% CI 0.07-0.26) were significantly lower in those receiving FT compared to FQ prophylaxis. A low incidence of medication-related side effects was observed. There were less observed infections due to FQ-resistant pathogens in those receiving FT prophylaxis. CONCLUSIONS: Patients who received FT prophylaxis were less likely than those who received FQ prophylaxis to develop infections overall, as well as severe and resistant infections after TRUSPB. Assessing the performance of FT in other geographic locations or in comparison to targeted prophylaxis based on risk assessment or rectal cultures is desired.

Aspects of urinary tract infections and antimicrobial resistance in hospitalized urology patients in Asia: 10-Year results of the Global Prevalence Study of Infections in Urology (GPIU).

OBJECTIVES: To assess Asian data from Global Prevalence Study on Infections in Urology (GPIU study) which has been performed more than 10 years. METHODS: Seventeen Asian countries participated in the GPIU study between 2004 and 2013. Data for these countries were collected from the web-based GPIU database. The point prevalence of urinary tract infections (UTI) and antimicrobial susceptibility of representative pathogens were analysed for Asian geographic regions. RESULTS: A total of 6706 patients (5271 male, 1435 female) were assessed during the study period, and 659 patients were diagnosed with a UTI (9.8%). Of these UTI patients, 436 were male and 223 were female. Mean patient age was 54.9 ± 19.3 years. Pyelonephritis and cystitis were the most common clinical diagnoses, representing 30.7% and 29.9% of patients, respectively. Escherichia coli was the most frequently identified uropathogen (38.7%). For the patients with urinary tract infection, cephalosporins were the most frequently used antibiotics (34.4%), followed by fluoroquinolones (24.1%), aminoglycosides (16.8%). Fluoroquinolone resistance was relatively high (ciprofloxacin 54.9%, levofloxacin 39.0%), and cephalosporin resistance 42% (42.5-49.4%). Of the antibiotics evaluated, uropathogens had maintained the highest level of susceptibility to amikacin and imipenem (24.9% and 11.3% resistance rates, respectively). CONCLUSION: Uropathogens in many Asian countries had high resistance to broad-spectrum antibiotics. Knowledge of regional and local resistance data and prudent use of antibiotics are important for proper management of UTI in Asian countries.

Non-Antibiotic Herbal Therapy (BNO 1045) versus Antibiotic Therapy (Fosfomycin Trometamol) for the Treatment of Acute Lower Uncomplicated Urinary Tract Infections in Women: A Double-Blind, Parallel-Group, Randomized, Multicentre, Non-Inferiority Phase III Trial.

INTRODUCTION: This randomized, controlled, Phase III non-inferiority clinical trial aimed to determine whether herbal therapy with Canephron® N (BNO 1045) is non-inferior to fosfomycin trometamol (FT) in treating acute lower uncomplicated urinary tract infections (uUTIs). MATERIALS AND METHODS: Women aged 18-70 years with typical symptoms of newly diagnosed acute lower uUTIs were randomized to BNO 1045 (n = 325) or FT (n = 334), with corresponding matched placebo. The primary endpoint was the proportion of patients who received additional antibiotics (ABs) to treat uUTIs between Days 1 and 38 ±3. RESULTS: Between Days 1 and 38, 238 (83.5%) patients in the BNO 1045 group and 272 (89.8%) patients in the FT group received no additional ABs. At a 15% non-inferiority margin, BNO 1045 was non-inferior to FT in treating uUTIs (non-AB rate difference: -6.26%; 95% CI -11.99 to -0.53%; 2-sided p = 0.0014). Adverse event rates were similar between groups, with higher rates of gastrointestinal disorders in the FT group and pyelonephritis in the BNO 1045 group. During the trial, no patient died or discontinued due to a treatment-related adverse event. CONCLUSIONS: BNO 1045 has the potential to reduce outpatient use of ABs for uUTIs and thus may have a significant impact on antimicrobial stewardship strategies. TRIAL REGISTRATION: NCT02639520, EudraCT number 2013-004529-99.

The 2017 Update of the German Clinical Guideline on Epidemiology, Diagnostics, Therapy, Prevention, and Management of Uncomplicated Urinary Tract Infections in Adult Patients: Part 1.

OBJECTIVES: We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. MATERIALS AND METHODS: An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, -EMBASE, and the Cochrane Library to identify literature published in 2010-2015. RESULTS: We provide 75 recommendations and 68 statements in the updated evidence- and consensus-based national clinical guideline. The diagnostics part covers practical recommendations on cystitis and pyelonephritis for each defined patient group. Clinical examinations, as well as laboratory testing and microbiological pathogen assessment, are addressed. CONCLUSION: In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients.

The 2017 Update of the German Clinical Guideline on Epidemiology, Diagnostics, Therapy, Prevention, and Management of Uncomplicated Urinary Tract Infections in Adult Patients. Part II: Therapy and Prevention.

BACKGROUND: We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. Results are published in 2 parts. Part 1 covers methods, the definition of patient groups, and diagnostics. This second publication focuses on treatment of acute episodes of cystitis and pyelonephritis as well as on prophylaxis of recurrent UTIs. MATERIALS AND METHODS: An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, EMBASE, and the Cochrane Library to identify literature published in 2010-2015. RESULTS: For the treatment of acute uncomplicated cystitis (AUC), fosfomycin-trometamol, nitrofurantoin, nitroxoline, pivmecillinam, and trimethoprim (depending on the local rate of resistance) are all equally recommended. Cotrimoxazole, fluoroquinolones, and cephalosporins are not recommended as antibiotics of first choice, for concern of an unfavorable impact on the microbiome. Mild to moderate uncomplicated pyelonephritis should be treated with oral cefpodoxime, ceftibuten, ciprofloxacin, or levofloxacin. For AUC with mild to moderate symptoms, instead of antibiotics symptomatic treatment alone may be considered depending on patient preference after discussing adverse events and outcomes. Primarily non-antibiotic options are recommended for prophylaxis of recurrent urinary tract infection. CONCLUSION: In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients.

Antimicrobial prophylaxis for transrectal ultrasound-guided prostate biopsy: fosfomycin trometamol, an attractive alternative.

OBJECTIVE: To compare fosfomycin trometamol (FT) and ciprofloxacin (CIP) for antibiotic prophylaxis in transrectal prostate biopsy (TR-PB). PATIENTS AND METHODS: Data for 1109 patients (mean age 66.7 ± 8.45) who underwent TR-PB between March to September 2015 in seven Italian urological institutions were retrospectively reviewed, of which 632 received FT (Group 1) and 477 received CIP (Group 2) for prophylaxis. We reviewed all urine culture results obtained after the procedure, all adverse drug reactions (ADRs) related to the drug and all febrile and/or symptomatic urinary tract infections (UTIs) occurring within 1 month after TR-PB. The rate of symptomatic UTIs and the rate of ADRs were considered the main outcome measures. RESULTS: In the total study population, 72/1109 (6.5 %) patients experienced symptomatic UTIs and among these 11 (0.9 % of total) had urosepsis. Out of 72, 53 (73.6 %) symptomatic UTIs were caused by fluoroquinolone-resistant strains. Out of 632, 10 (1.6 %) patients in Group 1 and 62/477 (12.9 %) patients in Group 2 had symptomatic UTIs (p < 0.001); in particular, 2/632 (0.3 %) patients in Group 1 and 9/477 (1.8 %) patients in Group 2 had urosepsis (p < 0.001). No differences were reported in terms of adverse events (0.6 vs 0.4 %; p = 0.70). A Charlson comorbidity index ≤1 and type of antimicrobial prophylaxis (FT) were found to be associated with a lower probability of symptomatic UTIs in the multivariate model. CONCLUSIONS: Antibiotic prophylaxis with FT for TR-PB had a lower rate of adverse events and a lower rate of symptomatic UTIs as compared with CIP. Fosfomycin trometamol appears as an attractive alternative prophylactic regimen in prostate biopsies.