Cefepime-Taniborbactam in Complicated Urinary Tract Infection.

BACKGROUND: Carbapenem-resistant Enterobacterales species and multidrug-resistant Pseudomonas aeruginosa are global health threats. Cefepime-taniborbactam is an investigational ß-lactam and ß-lactamase inhibitor combination with activity against Enterobacterales species and P. aeruginosa expressing serine and metallo-ß-lactamases. METHODS: In this phase 3, double-blind, randomized trial, we assigned hospitalized adults with complicated urinary tract infection (UTI), including acute pyelonephritis, in a 2:1 ratio to receive intravenous cefepime-taniborbactam (2.5 g) or meropenem (1 g) every 8 hours for 7 days; this duration could be extended up to 14 days in case of bacteremia. The primary outcome was both microbiologic and clinical success (composite success) on trial days 19 to 23 in the microbiologic intention-to-treat (microITT) population (patients who had a qualifying gram-negative pathogen against which both study drugs were active). A prespecified superiority analysis of the primary outcome was performed after confirmation of noninferiority. RESULTS: Of the 661 patients who underwent randomization, 436 (66.0%) were included in the microITT population. The mean age of the patients was 56.2 years, and 38.1% were 65 years of age or older. In the microITT population, 57.8% of the patients had complicated UTI, 42.2% had acute pyelonephritis, and 13.1% had bacteremia. Composite success occurred in 207 of 293 patients (70.6%) in the cefepime-taniborbactam group and in 83 of 143 patients (58.0%) in the meropenem group. Cefepime-taniborbactam was superior to meropenem regarding the primary outcome (treatment difference, 12.6 percentage points; 95% confidence interval, 3.1 to 22.2; P = 0.009). Differences in treatment response were sustained at late follow-up (trial days 28 to 35), when cefepime-taniborbactam had higher composite success and clinical success. Adverse events occurred in 35.5% and 29.0% of patients in the cefepime-taniborbactam group and the meropenem group, respectively, with headache, diarrhea, constipation, hypertension, and nausea the most frequently reported; the frequency of serious adverse events was similar in the two groups. CONCLUSIONS: Cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a safety profile similar to that of meropenem. (Funded by Venatorx Pharmaceuticals and others; CERTAIN-1 ClinicalTrials.gov number, NCT03840148.).

Patient outcomes by baseline pathogen resistance phenotype and genotype in CERTAIN-1, a Phase 3 study of cefepime-taniborbactam versus meropenem in adults with complicated urinary tract infection.

CERTAIN-1 was a Phase 3, double-blind, randomized, parallel group study of the efficacy and safety of cefepime-taniborbactam versus meropenem in the treatment of adults with complicated urinary tract infection (cUTI), including acute pyelonephritis. We determined susceptibility of Enterobacterales and Pseudomonas aeruginosa baseline pathogens to cefepime-taniborbactam and comparators and characterized ß-lactam resistance mechanisms. Microbiologic response and clinical response were assessed in patient subsets defined by baseline pathogens that were of cefepime-, multidrug-, or carbapenem-resistant phenotype or that carried ß-lactamase genes. Among Enterobacterales baseline pathogens, 26.8%, 4.1%, and 3.0% carried genes for extended-spectrum ß-lactamases (ESBLs), AmpC, and carbapenemases, respectively. Within each treatment group, while composite success rates at Test of Cure in resistant subsets by pathogen species were similar to those by pathogen overall, composite success rates in meropenem patients were numerically lower for cefepime-resistant Escherichia coli (9/19; 47.4%) and ESBL E. coli (13/25; 52.0%) compared with E. coli overall (62/100; 62.0%). Cefepime-taniborbactam achieved composite success in 7/8 (87.5%) patients with carbapenem-resistant Enterobacterales and 8/9 (88.9%) patients with Enterobacterales with a carbapenemase gene (5 OXA-48-group; 2 KPC-3; 2 NDM-1). Cefepime-taniborbactam also achieved composite success in 8/16 (50.0%) patients and clinical success in 13/16 (81.3%) patients with P. aeruginosa; corresponding rates were 4/7 (57.1%) and 6/7 (85.7%) for meropenem. Cefepime-taniborbactam demonstrated efficacy in adult cUTI patients with cefepime-, multidrug-, and carbapenem-resistant pathogens including pathogens with ESBL, AmpC, and carbapenemase genes. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT03840148.

How Might the Number of Lymph Nodes Removed during RARP Impact the Postoperative Outcomes?

INTRODUCTION: Symptomatic lymphocele remains a relevant complication after pelvic tumor surgery. This study aims to investigate how the number of lymph nodes removed may influence postoperative outcomes and if it increases the probability of detecting lymph node metastasis. METHODS: The study included 500 patients who underwent RARP including lymphadenectomy performed by a single surgeon. Patients were divided into two groups: group 1 consisted of 308 patients with 20 or fewer lymph nodes removed (mean 15), while group 2 had 192 patients with over 20 nodes removed (mean 27). Perioperative data were analyzed, and postoperative outcomes were compared between groups. RESULTS: Overall, lymph node metastasis was detected in 17.8% of men. In detail, out of 19.6 lymph nodes removed, an average of 3.14 lymph nodes per patient showed metastasis, with a slightly higher incidence of 19.7% in group 2 compared to 16.5% in group 1, though not statistically significant (p = 0.175). The number of lymph node metastases was significantly higher in group 2 patients (3.47) versus group 1 (2.37) (p = 0.048). All complications except symptomatic lymphoceles (p = 0.004) were not significantly different between groups. Univariate linear regression analysis revealed no correlation between the number of removed lymph nodes and symptomatic lymphocele. However, it did correlate with catheter days and readmissions. CONCLUSION: A correlation may exist between the number of lymph nodes removed during RARP and an increased incidence of complications, particularly symptomatic lymphocele. A more extensive PLND may result in prolonged catheter days and increased readmissions. With the increased extent of pelvic lymphadenectomy, the probability of detecting lymphogenic metastasis rises. The diagnostic value of PLND is well established. Further randomized trials are needed to weigh its necessity and extent.

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.

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.

Once-Daily Plazomicin for Complicated Urinary Tract Infections.

BACKGROUND: The increasing multidrug resistance among gram-negative uropathogens necessitates new treatments for serious infections. Plazomicin is an aminoglycoside with bactericidal activity against multidrug-resistant (including carbapenem-resistant) Enterobacteriaceae. METHODS: We randomly assigned 609 patients with complicated urinary tract infections (UTIs), including acute pyelonephritis, in a 1:1 ratio to receive intravenous plazomicin (15 mg per kilogram of body weight once daily) or meropenem (1 g every 8 hours), with optional oral step-down therapy after at least 4 days of intravenous therapy, for a total of 7 to 10 days of therapy. The primary objective was to show the noninferiority of plazomicin to meropenem in the treatment of complicated UTIs, including acute pyelonephritis, with a noninferiority margin of 15 percentage points. The primary end points were composite cure (clinical cure and microbiologic eradication) at day 5 and at the test-of-cure visit (15 to 19 days after initiation of therapy) in the microbiologic modified intention-to-treat population. RESULTS: Plazomicin was noninferior to meropenem with respect to the primary efficacy end points. At day 5, composite cure was observed in 88.0% of the patients (168 of 191 patients) in the plazomicin group and in 91.4% (180 of 197 patients) in the meropenem group (difference, -3.4 percentage points; 95% confidence interval [CI], -10.0 to 3.1). At the test-of-cure visit, composite cure was observed in 81.7% (156 of 191 patients) and 70.1% (138 of 197 patients), respectively (difference, 11.6 percentage points; 95% CI, 2.7 to 20.3). At the test-of-cure visit, a higher percentage of patients in the plazomicin group than in the meropenem group were found to have microbiologic eradication, including eradication of Enterobacteriaceae that were not susceptible to aminoglycosides (78.8% vs. 68.6%) and Enterobacteriaceae that produce extended-spectrum ß-lactamases (82.4% vs. 75.0%). At late follow-up (24 to 32 days after initiation of therapy), fewer patients in the plazomicin group than in the meropenem group had microbiologic recurrence (3.7% vs. 8.1%) or clinical relapse (1.6% vs. 7.1%). Increases in serum creatinine levels of 0.5 mg or more per deciliter (≥40 µmol per liter) above baseline occurred in 7.0% of patients in the plazomicin group and in 4.0% in the meropenem group. CONCLUSIONS: Once-daily plazomicin was noninferior to meropenem for the treatment of complicated UTIs and acute pyelonephritis caused by Enterobacteriaceae, including multidrug-resistant strains. (Funded by Achaogen and the Biomedical Advanced Research and Development Authority; EPIC ClinicalTrials.gov number, NCT02486627.).

Physiological and pharmacological impact of oxytocin on epididymal propulsion during the ejaculatory process in rodents and men.

During the emission phase of ejaculation, the sperm is driven from the cauda epididymidis, where it is stored, through the vas deferens by strong contractions. These contractions are thought of as being mainly induced by the sympathetic nervous system and the neurotransmitter noradrenaline. In the present study, we investigated the effect of oxytocin (suggested to exert effects during ejaculation as well) on defined segments of the rat and human epididymis using live imaging. Our results indicate that it is the very last part of the epididymis, segment 19 (S19) in rat and likewise segment 9 in human, which responds in a uniquely strong and rapid manner to oxytocin (similar to noradrenaline). Because of the complex nature of this contractile response, we developed an imaging analysis method, which allowed us to quantify multidirectional contractions and to display them using heat maps. The reaction of S19 to oxytocin was concentration-dependent and could be inhibited by pretreatment with oxytocin antagonists (atosiban and cligosiban), but not with an arginine vasopressin 1A antagonist (SR49059). In both rat and human tissue, pretreatment with the alpha-1 adrenoreceptor antagonist tamsulosin inhibited the response to noradrenaline, whereas the effect of oxytocin was unimpaired. Our data (from men and rodents) strongly suggest that the hormone oxytocin is involved in the ejaculatory process. Thus, oxytocin-based medications might be a promising non-adrenergic treatment option for ejaculatory disorders. Additionally, we propose that S19 could be an advantageous model (detecting very low concentrations of oxytocin) to test the bioactivity of new oxytocin agonists and oxytocin antagonists.

Comparative Analysis of Guideline Adherence between Germany and Austria by Using the Example of Uncomplicated Urinary Tract Infections.

BACKGROUND: Medical guidelines represent the evidence-based state of the art of their scientific field. They aim to guide decisions for physicians and patients about appropriate health care for specific clinical circumstances. However, guideline recommendations are often not adhered to in clinical practice. In particular, a large discrepancy exists regarding the treatment of uncomplicated urinary tract infections. To date, just a few studies addressed the potential reasons for these guideline violations. OBJECTIVES: This investigation aimed to identify and complement reasons for the nonadherence to guideline recommendations. METHODS: A survey amongst a total of 563 German and Austrian urologists identified physician- and patient-related factors contributing to this current state. RESULTS: The physician's personal experience, the lack of applicability to individual patients, and shortage of time were identified as crucial barriers for the physician. Patient-related barriers were poor experience with the antibiotic, fear of collateral damage, and inadequate information about the disease and its therapy. CONCLUSIONS: We suggest modifying guideline designs by including abstracts and flowcharts appropriate for daily use and separate patient instructions to improve guideline compliance. Furthermore, guideline authors should communicate updates in a timely and accessible manner. Presentations at scientific congresses increase visibility and enhance the dialogue with colleagues.

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.

Hyperbaric Oxygenation in the Treatment of Fournier's Gangrene: A Systematic Review.

INTRODUCTION: Fournier's gangrene (FG) is a sporadic, life-threatening, necrotizing infection affecting the perineum, perineal region, and genitals. Hyperbaric oxygenation (HBO) improves tissue perfusion and promotes angiogenesis and collagen synthesis. Despite these positive effects of HBO, the indication and the effects on outcome as adjunct therapy in FG remain controversial. Consequently, we decided to perform a systematic review to compare the treatment of FG with or without the use of HBO as an adjunct therapy. MATERIALS AND METHODS: We performed a systematic review following the recommendations provided in the Cochrane Handbook of systematic Reviews and the PRISMA reporting guidelines. Due to the paucity of data and a suspected lack of randomized controlled trials, we considered all the available information for this systematic review. RESULTS: The literature search for primary studies yielded 79 results. Finally, 13 studies were considered, which included a total of 376 patients with FG, of whom 202 received HBO therapy. Five of these studies had a retrospective case-control design. However, these 5 studies included a total of 319 patients; 145 of these patients were treated with adjunct HBO therapy. Overall, this leads to a mortality rate of 16.6% in the HBO group and 25.9% in the non-HBO group. Overall, risk of bias was assessed as moderate to high. CONCLUSIONS: We conclude that despite the risk of bias, HBO has potential as an adjunct in FG treatment, but it is challenging to carry out further studies, mainly due to the rareness of FG and availability of HBO.

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.

Escherichia coli Resistance to Fluoroquinolones in Community-Acquired Uncomplicated Urinary Tract Infection in Women: a Systematic Review.

Antibiotic resistance is a threat to public health, and uncomplicated urinary tract infections (uUTIs) are an example of this concern. This systematic review (International Prospective Register of Systematic Reviews [PROSPERO] ID: CRD42020156674) is the first to determine the prevalence of Escherichia coli resistance to fluoroquinolones in women with community-acquired uUTI. PubMed and Embase searches were conducted; 38 studies fulfilled eligibility criteria and were included in the systematic review. Within Europe, ciprofloxacin resistance in E. coli isolates varied between countries and increased in some from 2006 to 2008 and 2014 to 2016, specifically in the United Kingdom (0.5% to 15.3%), Germany (8.7% to 15.1%), and Spain (22.9% to 30.8%), although methodologies and settings were often not comparable. In Asia, there was a substantial increase in ciprofloxacin resistance during 2008 to 2014 from 25% to more than 40%. In North America, resistance to ciprofloxacin also increased between 2008 and 2017, from 4% to 12%. Data exploring different age groups did not show a consistent relationship with resistance, whereas two studies found that fluoroquinolone resistance was higher in postmenopausal women than premenopausal women. One study indicated a link between fluoroquinolone resistance and uUTI recurrence. These findings may have implications for the empirical treatment of uUTI with fluoroquinolones globally, but more data are needed to fully understand regional situations and impact patient management.

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.

Antibiotic resistance, hospitalizations, and mortality related to prostate biopsy: first report from the Norwegian Patient Registry.

BACKGROUND: A 68-year-old man died of cerebral arterial embolism 6 days after transrectal prostate biopsy with a single p.o. dose of trimethoprim sulfamethoxazole (TMP-SMX) as prophylaxis. The case precipitated analysis of local antibiotic resistance and complication rates. MATERIALS AND METHODS: Data on E. coli resistance from Oslo University Hospital and national data on hospitalizations and mortality after biopsy were retrieved from local microbiology files and the Norwegian Patient Registry (NPR) 2011-2017. RESULTS: Urine E. coli resistance against TMP-SMX increased from 35% in 2013 to more than 60% in 2015. For ciprofloxacin, the resistance increased from 15% in 2013 to about 45% in 2016. The highest annual E. coli resistance in blood cultures for TMP-SMX and ciprofloxacin was 37% and 28%, respectively. 10% of patients were hospitalized with a diagnosis of infection within the first 60 days after biopsy and there was a relative increase in mortality rate of 261% within the first 30 days. Due to the severity of the figures, the story and the NPR data were published in Norway's leading newspaper and were succeeded by a series of chronicles and commentaries. CONCLUSIONS: Several critical points of the biopsy procedure were not performed according to current standards. We believe that the patient might have died of septic embolism after biopsy. As a result of the findings and the debate, local practice was changed from transrectal to transperineal prostate biopsies.

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.

Novel imaging of the prostate reveals spontaneous gland contraction and excretory duct quiescence together with different drug effects.

Prostate carcinoma and benign prostate hyperplasia (BPH) with associated lower urinary tract symptoms (LUTS) are among the most prevalent and clinically relevant diseases in men. BPH is characterized by an enlargement of prostate tissue associated with increased tone of smooth muscle cells (SMCs) which surround the single glands composing the prostate. Secretions of the glands leave the prostate through local excretory ducts during the emission phase of ejaculation. Pharmacological treatment of BPH suggests different local drug targets based on reduction of prostate smooth muscle tone as the main effect and disturbed ejaculation as a common side effect. This highlights the need for detailed investigation of single prostate glands and ducts. We combined structural and functional imaging techniques-notably, clear lipid-exchanged, acrylamide-hybridized rigid imaging/immunostaining/ in situ hybridization-compatible tissue-hydrogel (CLARITY) and time-lapse imaging-and defined glands and ducts as distinct SMC compartments in human and rat prostate tissue. The single glands of the prostate (comprising the secretory part) are characterized by spontaneous contractions mediated by the surrounding SMCs, whereas the ducts (excretory part) are quiescent. In both SMC compartments, phosphodiesterase (PDE)-5 is expressed. PDE5 inhibitors have recently emerged as alternative treatment options for BPH. We directly visualized that the PDE5 inhibitors sildenafil and tadalafil act by reducing spontaneous contractility of the glands, thereby reducing the muscle tone of the organ. In contrast, the ductal (excretory) system and thus the prostate's contribution to ejaculation is unaffected by PDE5 inhibitors. Our differentiated imaging approach reveals new details about prostate function and local drug actions and thus may support clinical management of BPH.-Kügler, R., Mietens, A., Seidensticker, M., Tasch, S., Wagenlehner, F. M., Kaschtanow, A., Tjahjono, Y., Tomczyk, C. U., Beyer, D., Risbridger, G. P., Exintaris, B., Ellem, S. J., Middendorff, R. Novel imaging of the prostate reveals spontaneous gland contraction and excretory duct quiescence together with different drug effects.

Perioperative antibiotic prophylaxis for stone therapy.

PURPOSE OF REVIEW: To give an overview about state-of-the-art antibiotic prophylaxis in urolithasis therapy and focus on recent publications in this field. RECENT FINDINGS: The number of high-quality publications within the recent time is limited. Preoperative inflammatory blood parameters like C-reactive protein and erythrocyte-sedimentation rate might help in prediction of postoperative systemic inflammatory response syndrome (SIRS) after percutaneous nephrolithotomy (PCNL). White blood cell count is nonpredictive for urinary tract infection (UTI) in patients with acute renal colic. In patients with low risk for infectious complications, antibiotic prophylaxis during shock-wave lithotripsy (SWL) is unnecessary and single-dose antibiotics are comparably effective as prolonged antibiotic usage during PCNL and ureterorenoscopy (URS). SUMMARY: Current findings support the American Urological Association (AUA) and European Association of Urology (EAU) guideline recommendations for a risk-adapted minimal antibiotic usage. Single-dose antibiotic prophylaxis is sufficient for low-risk PCNL and URS. For SWL no antibiotic prophylaxis is needed.

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.