Community-onset urosepsis: incidence and risk factors for 30-day mortality - a retrospective cohort study.

BACKGROUND: Urosepsis is a life-threatening condition that needs to be addressed without delay. Two critical issues in its management are: (1) Appropriate empirical antibiotic therapy, considering the patients general condition, comorbidity, and the pathogen expected; and (2) Timing of imaging to identify obstruction requiring decompression. OBJECTIVES: To identify risk factors associated with 30-day mortality in patients with urosepsis. METHODS: From a cohort of 1,605 community-onset bloodstream infections (CO-BSI), 282 patients with urosepsis were identified in a Swedish county 2019-2020. Risk factors for mortality with crude and adjusted odds ratios were analysed using logistic regression. RESULTS: Urosepsis was found in 18% (n = 282) of all CO-BSIs. The 30-day all-cause mortality was 14% (n = 38). After multivariable analysis, radiologically detected urinary tract disorder was the predominant risk factor for mortality (OR = 4.63, 95% CI = 1.47-14.56), followed by microbiologically inappropriate empirical antibiotic therapy (OR = 4.19, 95% CI = 1.41-12.48). Time to radiological diagnosis and decompression of obstruction for source control were also important prognostic factors for survival. Interestingly, 15% of blood cultures showed gram-positive species associated with a high 30-day mortality rate of 33%. CONCLUSION: The 30-day all-cause mortality from urosepsis was 14%. The two main risk factors for mortality were hydronephrosis caused by obstructive stone in the ureter and inappropriate empirical antibiotic therapy. Therefore, early detection of any urinary tract disorder by imaging followed by source control as required, and antibiotic coverage of both gram-negative pathogens and gram-positive species such as E. faecalis to optimise management, is likely to improve survival in patients with urosepsis.

Experimental in vivo model to evaluate the impact of Cernitin™ on pain response on induced chronic bladder inflammation.

OBJECTIVE: Inflammation of the urinary bladder may cause burdensome pain also called bladder pain syndrome (BPS). A limitation in understanding BPS pathophysiology is the lack of appropriate preclinical model. Previously published clinical and preclinical studies revealed positive impact of Cernitin™ on pain relief in chronic prostatitis. The objective of this study was to evaluate the effects of Cernitin™ on induced inflammation of the urinary bladder in rats. We also sought to identify biomarkers which might play a role in the management of BPS. MATERIALS AND METHODS: Cystitis was induced by injection of cyclophosphamide (CYP) in female rats. Thereafter, animals were randomly divided into four treatment groups and two control groups. Evaluation of pain scores was assessed by von Frey assay. Expression of pain- and pro-inflammatory biomarkers was determined by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. RESULTS: Treatments with Cernitin™ displayed significant anti-nociceptive effects on CYP-induced visceral pain (p < .01). In contrast, vehicle-treated animals showed high pain score even at the lowest force. Furthermore, results of ELISA showed that Cernitin™-treated animals had significantly reduced levels of COX-2 (T60, p < .01; GBX, p < .05) in bladder tissue homogenate. Immunohistochemical (IHC) staining of bladder tissues showed that Cernitin™-treated animals exhibited less CD45-positive cells, while massive CD45-positive cells infiltration was detected in vehicle-treated animals. IHC also revealed lower SP and PGD2 expression levels in Cernitin™-treated tissues. CONCLUSIONS: Cernitin™ components reduced pain score and inflammatory marker COX-2. Our findings suggest a potential therapeutic role for Cernitin™ in the management of BPS.

The effects of Cernitin® on inflammatory parameters and benign prostatic hyperplasia: An in vitro study.

The pollen extract Cernitin® is widely used for treatment of benign prostatic hyperplasia (BPH) and non-bacterial chronin prostatitis. However, little is known about the underlying molecular mechanisms to explain the clinical effects of Cernitin®. In this study, we sought to investigate the cellular mechanisms by which Cernitin® induces its effects on human prostatic cell lines BPH-1 and WPMY-1 and primary human peripheral blood mononuclear cells (hPBMCs) in vitro. We examined the effects of Cernitin® formulas T60 and GBX on the protein expression, proliferation, and cytokines production. Results revealed that Cernitin® upregulated antiinflammatory cytokine interleukin (IL)-10 and its receptors IL-10RA and IL-10B in addition to the upregulation of tumour necrosis factor-related apoptosis-inducing ligand in hPBMC. Interestingly, the levels of proinflammatory cytokines IL-6 and IL-8 were also increased. Furthermore, Cernitin® had significantly increased the level of IL-10 in BPH-1 and WPMY-1 cells. The level of IL-6 was also significantly increased in these cells although both T60 and GBX inhibited STAT-3 phosphorylation. Moreover, Cernitin® formulas had significantly reduced androgen receptor and prostate-specific antigen protein expression in stromal cells (p < .05). Treatment with GBX and T60 had significantly inhibited proliferation of BPH (p < .001) and stromal cells (p < .05), in a dose-dependent manner. Taken together, treatment with Cernitin® showed to regulate cytokines level in both prostatic cell lines and hPBMCs and it was associated with decreased androgen receptor and prostate-specific antigen levels WPMY-1 cells.

Asymptomatic Bacteriuria is Harmless and Even Protective: Don't Treat if You Don't Have a Very Specific Reason.

Symptom-free bacterial colonization of the lower urinary tract in an otherwise healthy individual was long misunderstood. Our current understanding is based on solid research proving that asymptomatic bacteriuria (ABU) is harmless and even protective against symptomatic urinary tract infection episodes. Thus, ABU should not be treated in patients with the exception of before endosurgery and, until we have accumulated more knowledge, in pregnant women.

Antimicrobial Stewardship: What We All Just Need to Know.

CONTEXT: Microbial resistance to antibiotics is increasing while antimicrobials are limited. Responsible use is necessary. OBJECTIVE: Describe the present acquisitions of antimicrobial stewardship programmes (ASPs) in general and in urology. EVIDENCE SYNTHESIS: Well-designed ASPs have an impact on reducing treatment duration, shortening intravenous treatment in favour of oral targeted therapy, and reducing the total antibiotic prescription. Moreover, the hospital length of stay can potentially be reduced without hazard for the patient. CONCLUSIONS: It is recommended to set up an ASP for education and feedback as standard in urological practice. The exact design of the ASP should be tailored to regional prerequisites.

Can routine outpatient follow-up of patients with bladder cancer be improved? A multicenter prospective observational assessment of blue light flexible cystoscopy and fulguration.

BACKGROUND: The aim of this prospective cohort study was to determine the feasibility of incorporating blue light flexible cystoscopy (BLFC) and biopsy/fulguration into routine outpatient follow-up of non-muscle invasive bladder cancer patients. METHODS: The study included patients with non-muscle-invasive bladder cancer (NMIBC) who were scheduled for routine follow-up. Hexaminolevulinate was instilled in the outpatient department, and the bladder was examined under white light and then with BLFC. Biopsies were taken from all suspicious lesions. Small tumors and suspicious lesions were fulgurated on site; patients with larger lesions were referred to the operating room for resection. RESULTS: The study included 69 patients, with a mean age of 70 years (range 33-89 years) and a mean duration since NMIBC diagnosis of 8 years. Most patients had high-grade cancer at initial diagnosis (52/69) and were at high risk of recurrence (48/69). Two patients per hour could be assessed using outpatient BLFC. Preparation and instillation of hexaminolevulinate took less than 10 minutes per patient, and patients had an additional waiting time of 45-60 minutes following instillation, while the hexaminolevulinate solution was retained in the bladder before examination. Eleven patients had histologically confirmed tumors that were identified using both white light flexible cystoscopy and BLFC. An additional three patients had tumors that were identified by BLFC only: two with Ta tumors and one with carcinoma in situ. Of the 14 patients with confirmed tumors, 11 could be managed on site with fulguration, whereas three were referred to the operating room. No adverse events attributable to BLFC were reported. CONCLUSION: Routine outpatient management of patients with NMIBC using BLFC and on-site biopsy/fulguration is feasible, despite the additional time required for hexaminolevulinate instillation, and appears to allow early detection of recurrent lesions, which can be fulgurated without the need for hospitalization.

Tailored perioperative antimicrobial prophylaxis in urological surgery: myth or reality?

PURPOSE OF REVIEW: The controversies surrounding perioperative antimicrobial prophylaxis (AMP) are about the use and especially misuse of antibiotics. The overall lack of evidence to facilitate a rational perioperative AMP policy in urological surgery and the postoperative infectious complications remain a challenge. Therefore, a basic tool to aid decision-making would be useful. A model based on the patients' risk factors, the level of contamination and grading of surgical procedures is discussed. RECENT FINDINGS: A series of studies have shown that infectious complications and healthcare-associated infections remain consistently at an average of 10%, with a great variation in frequency dependent on the patients' preoperative status and the type, severity and contamination level of the surgical procedure. Preoperative patient assessment and preparation are key factors for well tolerated surgery and recovery. Adherence to the guidelines appears to reduce both the prescription of antimicrobials and the total costs without risking the patient outcome. Several studies of a series of interventions such as cystoscopy, endoscopic stone surgery and selected clean-contaminated interventions give support to the model. Bacteriuria, upgrading the patient to the contaminated level, requires preoperative control. SUMMARY: The discussed model assists the urologists in decision-making on perioperative AMP and contributes to a responsible use of antibiotics.

Catheter-associated urinary tract infections and other infections in patients hospitalized for acute stroke: A prospective cohort study of two different silicone catheters.

OBJECTIVE: Catheter-associated urinary tract infection (CAUTI) is the most common healthcare-associated infection. The primary aim of this study was to investigate whether the use of a silicone catheter coated with an ultrathin layer of a combination of the noble metals gold, palladium and silver (BIP™-silicone catheter) could reduce the incidence of CAUTI and antibiotic prescription compared with a standard silicone catheter in a cohort of acute neurological patients suffering primarily from stroke. At the same time, all infectious events requiring prescription of an antimicrobial agent were registered and are reported. MATERIALS AND METHODS: The study was designed as a crossover cohort study enrolling men and women aged over 18 years, requiring emergency management for stroke including the insertion of an indwelling catheter. Data on patient characteristics, urinary tract infections (UTIs), other infectious events and all antibiotic prescriptions were recorded prospectively. RESULTS: The patients' characteristics differed in the two centres in terms of age but not in diagnosis distribution. UTIs were recorded in 78 (24.2%) of the patients, ahead of pulmonary tract infections (n = 65; 20.2%). There was no difference in terms of CAUTI in the two catheter groups, even in subgroups with catheter treatment for 1 week or less. The patients with a diagnosed UTI required 3.5 more days of hospitalization than those without a UTI. CONCLUSION: CAUTIs were the most frequent healthcare-associated infections, slightly ahead of pulmonary tract infections. No advantages of the coated catheter could be found in this cohort of critically ill patients.

Asymptomatic Bacteriuria in Clinical Urological Practice: Preoperative Control of Bacteriuria and Management of Recurrent UTI.

Asymptomatic bacteriuria (ABU) is a common clinical condition that often leads to unnecessary antimicrobial use. The reduction of antibiotic overuse for ABU is consequently an important issue for antimicrobial stewardship and to reduce the emergence of multidrug resistant strains. There are two issues in everyday urological practice that require special attention: the role of ABU in pre-operative prophylaxis and in women affected by recurrent urinary tract infections (rUTIs). Nowadays, this is the time to think over our practice and change our way of thinking. Here, we aimed to summarize the current literature knowledge in terms of ABU management in patients undergoing urological surgery and in patients with rUTIs. In the last years, the approach to patient with ABU has changed totally. Prior to all surgical procedures that do not enter the urinary tract, ABU is generally not considered as a risk factor, and screening and treatment are not considered necessary. On the other hand, in the case of all procedures entering the urinary tract, ABU should be treated in line with the results of a urine culture obtained before the procedure. In patients affected by rUTIs, ABU can even have a protective role in preventing symptomatic recurrence, particularly when Enterococcus faecalis (E. faecalis) has been isolated.

Contemporary Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

CONTEXT: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition that causes severe symptoms, bother, and quality-of-life impact in the 8.2% of men who are believed to be affected. Research suggests a complex pathophysiology underlying this syndrome that is mirrored by its heterogeneous clinical presentation. Management of patients diagnosed with CP/CPPS has always been a formidable task in clinical practice. Due to its enigmatic etiology, a plethora of clinical trials failed to identify an efficient monotherapy. OBJECTIVE: A comprehensive review of published randomized controlled trials (RCTs) on the treatment of CP/CPPS and practical best evidence recommendations for management. EVIDENCE ACQUISITION: Medline and the Cochrane database were screened for RCTs on the treatment of CP/CPPS from 1998 to December 2014, using the National Institutes of Health Chronic Prostatitis Symptom Index as an objective outcome measure. Published data in concert with expert opinion were used to formulate a practical best evidence statement for the management of CP/CPPS. EVIDENCE SYNTHESIS: Twenty-eight RCTs identified were eligible for this review and presented. Trials evaluating antibiotics, α-blockers, anti-inflammatory and immune-modulating substances, hormonal agents, phytotherapeutics, neuromodulatory drugs, agents that modify bladder function, and physical treatment options failed to reveal a clear therapeutic benefit. With its multifactorial pathophysiology and its various clinical presentations, the management of CP/CPPS demands a phenotypic-directed approach addressing the individual clinical profile of each patient. Different categorization algorithms have been proposed. First studies applying the UPOINTs classification system provided promising results. Introducing three index patients with CP/CPPS, we present practical best evidence recommendations for management. CONCLUSIONS: Our current understanding of the pathophysiology underlying CP/CPPS resulting in this highly variable syndrome does not speak in favor of a monotherapy for management. No efficient monotherapeutic option is available. The best evidence-based management of CP/CPPS strongly suggests a multimodal therapeutic approach addressing the individual clinical phenotypic profile. PATIENT SUMMARY: Chronic prostatitis/chronic pelvic pain syndrome presents a variable syndrome. Successful management of this condition is challenging. It appears that a tailored treatment strategy addressing individual patient characteristics is more effective than one single therapy.

Antimicrobial resistance in urosepsis: outcomes from the multinational, multicenter global prevalence of infections in urology (GPIU) study 2003-2013.

OBJECTIVE: Primary objective was to identify the (1) relationship of clinical severity of urosepsis with the pathogen spectrum and resistance and (2) appropriateness of using the pathogen spectrum and resistance rates of health-care-associated urinary tract infections (HAUTI) as representative of urosepsis. The secondary objective was to provide an overview of the pathogens and their resistance profile in patients with urosepsis. POPULATION AND METHODS: A point prevalence study carried out in 70 countries (2003-2013). Population studied included; 408 individuals with microbiologically proven urosepsis, 1606 individuals with microbiological proof of HAUTI and 27,542 individuals hospitalised in urology wards. Main outcomes are pathogens and resistance identified in HAUTIs and urosepsis including its clinical severity. A statistical model that included demographic factors (study year, geographical location, hospital setting) was used for analysis. RESULTS: Amongst urology practices, the prevalence of microbiologically proven HAUTI and urosepsis was 5.8 and 1.5 %, respectively. Frequent pathogens in urosepsis were E. coli (43 %), Enterococcus spp. (11 %), P. aeruginosa (10 %) and Klebsiella spp. (10 %). Resistance to commonly prescribed antibiotics was high and rates ranged from 8 % (imipenem) to 62 % (aminopenicillin/ß lactamase inhibitors); 45 % of Enterobacteriaceae and 21 % of P. aeruginosa were multidrug-resistant. Resistance rates in urosepsis were higher than in other clinical diagnosis of HAUTI (Likelihood ratio <0.05). CONCLUSIONS: It is not appropriate to use the pathogen spectrum and resistance rates of other HAUTIs as representative of urosepsis to decide on empirical treatment of urosepsis. Resistance rates in urosepsis are high, and precautions should be made to avoid further increase.

How to Use Antimicrobial Prophylaxis in Urological Procedures.

A revision of clinical practice in terms of antimicrobial prophylaxis is urgently needed starting from: (1) obtaining information about local pathogen profiles and antimicrobial resistance, (2) evaluating all patient-related risk factors for the development of infectious complications, (3) and prescribing antimicrobials according to the principles of the European Association of Urology guidelines.

Grey Zones in the Field of Urinary Tract Infections.

Urinary tract infections are a very common clinical problem with various knowledge gaps requiring urgent attention in areas including pathophysiology, diagnosis, antibiotic resistance, and prophylaxis. These grey zones preclude optimal management of urologic patients.

Antibiotic stewardship: a call for action by the urologic community.

Increasing antibiotic resistance and lack of new antibiotics in the near future calls for a variety of coordinated strategies called "Antibiotic stewardship", to improve antibiotic use with the goal of enhancing patient health outcomes and reducing emergence of resistance to antibiotics.

Infective complications after prostate biopsy: outcome of the Global Prevalence Study of Infections in Urology (GPIU) 2010 and 2011, a prospective multinational multicentre prostate biopsy study.

BACKGROUND: Infection is a serious adverse effect of prostate biopsy (P-Bx), and recent reports suggest an increasing incidence. OBJECTIVE: The aim of this multinational multicentre study was to evaluate prospectively the incidence of infective complications after P-Bx and identify risk factors. DESIGN, SETTING, AND PARTICIPANTS: The study was performed as an adjunct to the Global Prevalence Study of Infections in Urology (GPIU) during 2010 and 2011. Men undergoing P-Bx in participating centres during the 2-wk period commencing on the GPIU study census day were eligible. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Baseline data were collected and men were questioned regarding infective complications at 2 wk following their biopsy. The Fisher exact test, Student t test, Mann-Whitney U test, and multivariate regression analysis were used for data analysis. RESULTS AND LIMITATIONS: A total of 702 men from 84 GPIU participating centres worldwide were included. Antibiotic prophylaxis was administered prior to biopsy in 98.2% of men predominantly using a fluoroquinolone (92.5%). Outcome data were available for 521 men (74%). Symptomatic urinary tract infection (UTI) was seen in 27 men (5.2%), which was febrile in 18 (3.5%) and required hospitalisation in 16 (3.1%). Multivariate analysis did not identify any patient subgroups at a significantly higher risk of infection after P-Bx. Causative organisms were isolated in 10 cases (37%) with 6 resistant to fluoroquinolones. The small sample size per participating site and in compared with other studies may have limited the conclusions from our study. CONCLUSIONS: Infective complications after transrectal P-Bx are important because of the associated patient morbidity. Despite antibiotic prophylaxis, 5% of men will experience an infective complication, but none of the possible factors we examined appeared to increase this risk. Our study confirms a high incidence of fluoroquinolone resistance in causative bacteria.