Glycomimetics as Candidates for Treatment and Prevention of Catheter-associated Biofilms Formed by Pseudomonas aeruginosa.

Bacteria develop biofilms for protection and persistent colonization. Biofilms of pathogenic bacteria can lead to serious medical problems. Bacterial biofilms on catheters used in the treatment of urinary tract diseases represent a major challenge for antibiotic therapy. Several attempts to eradicate biofilms using classical antibiotics and various alternatives, including antibiotic treatment of surfaces, surfaces that release silver ions, and surfaces with anti-adhesive properties, have not shown clinical efficacy in biofilm prevention or removal. Pseudomonas aeruginosa is one of the most problematic biofilm-forming uropathogens and accounts for approximately 10% of urinary tract infections. Novel glycomimetics that inhibit bacterial lectins have shown promising results in the prevention of P. aeruginosa biofilms and in interference with bacterial virulence. This mini-review summarizes the status of glycomimetic development and provides a perspective on their use in clinical practice. PATIENT SUMMARY: For patients with recurrent urinary tract infections and patients needing long-term catheter use to manage urinary problems, biofilms formed by bacteria can be a problem and are difficult to treat. New compounds that mimic carbohydrates, called glycomimetics, have shown promise in inhibiting these bacteria and the biofilms they form. More research on these compounds is needed before they can be used to treat patients.

Discovery of Antimicrobial Peptides in Urinary Tract Infections.

Antimicrobial peptides (AMPs) play a pivotal role in the innate immune system as a frontline defense against microbial threats. AMPs can serve as biomarkers and alternative antibiotics, overcoming mortality related to multidrug-resistant pathogens in urinary tract infections (UTIs). While the relevance of AMPs in UTIs has been validated and AMP drugs approved by the US Food and Drug Administration are in clinical use, information about their modification status, regulation, and mechanism of action remains sparse. Only a small fraction of sequences with potential AMP activity, predicted on the basis of known AMP characteristics, have been validated. Elucidation of the global profile of AMPs in the bladder, kidney, and urine under UTI conditions would facilitate an in-depth, disease-specific understanding of the innate immune system and the development of tailored AMP biomarkers and antibiotics. This mini-review focuses on a comprehensive strategy for global profiling and validation of AMPs in UTIs that incorporates AMP data repositories, prediction algorithms, and proteomics for healthy individuals and UTI patients. PATIENT SUMMARY: Short protein molecules called peptides that have antimicrobial activity show promise for the treatment of urinary tract infections. More research and testing of naturally occurring and synthetic peptides with this activity are needed to fully understand how they can help in patient care.

Novel Antibiotics for Urinary Tract Infection (UTI): The EAGLE 2 and EAGLE-3 Trials for Uncomplicated UTI, and the CERTAIN-1 Trial for Complicated UTI.

Two novel antibiotics have been evaluated for the treatment of urinary tract infection (UTI). Gepotidacin was an efficacious first-in-class oral antibiotic in uncomplicated UTI in comparison to nitrofurantoin. Cefepime/taniborbactam was superior to meropenem in complicated UTI and acute pyelonephritis.

Influence of Kidney Environment Parameters on Antibiotic Efficacy Against Uropathogenic Escherichia coli.

BACKGROUND AND OBJECTIVE: Urinary tract infections (UTIs) are common infections affecting the urinary system, predominantly caused by bacterial pathogens, with Escherichia coli being the most frequent pathogen. Infections of the kidney (eg, pyelonephritis) are severe and challenging to treat, due to the specific tissue microenvironment. In this study, the influence of different parameters mimicking the kidney environment on the effectiveness of antibiotics prescribed for pyelonephritis on the growth of uropathogenic strains was analyzed. METHODS: To investigate the influence of different factors mimicking the kidney environment, we tested the effect of different kidney-representative concentrations of sodium chloride and urea, and different pH values on the efficacy of ertapenem, levofloxacin, and ceftriaxone. The effectiveness was assessed by determining the minimal inhibitory concentrations (MICs) against various E. coli strains. KEY FINDINGS AND LIMITATIONS: The study revealed that pH significantly influences the MIC values of levofloxacin. Acidification of the pH led to an increase of the MIC values, while an alkaline pH had the opposite effect. The influence of sodium chloride and urea concentrations was strain and antibiotic specific. Since three different antibiotics were tested in this study, further research with additional antibiotics is warranted. CONCLUSIONS AND CLINICAL IMPLICATIONS: These results suggest that the physicochemical conditions within the kidney can substantially influence the success of antibiotic therapy for pyelonephritis. Therefore, it is crucial for clinicians to consider these factors when selecting and dosing antibiotics. Further research is needed to evaluate a broader range of antibiotics and additional environmental parameters, to develop a more comprehensive understanding of how the kidney environment affects antimicrobial activity. This knowledge will be vital in optimizing treatment strategies for pyelonephritis, ultimately improving patient outcomes. PATIENT SUMMARY: The physicochemical conditions within the kidney influence the success of antibiotic therapy for pyelonephritis. Our findings are vital in optimizing treatment strategies and will ultimately improve patient outcomes.

Keep it Simple: A Proposal for a New Definition of Uncomplicated and Complicated Urinary Tract Infections from the EAU Urological Infections Guidelines Panel.

The European Association of Urology Urological Infections Guidelines Panel is proposing a new classification scheme for categorizing urinary tract infections (UTIs) into uncomplicated and complicated types. This classification would provide clarity and facilitate effective clinical management of UTIs, and acknowledges the importance of addressing clinical and sex-specific nuances in the care of individual patients.

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.

Descending perineal syndrome cure by deep transversus perinei ligament repair: surgical options.

Descending perineal syndrome (DPS) was described by Parks et al. as descent of the anus on straining, typically 3-4 cm below a line drawn from the coccyx to the lower end of the. DPS is associated with obstructed defecation, with increased bulging of the perineum with straining, although perineal descent can also be seen at rest. In their review, Chaudhry and Tarnay stated: "It is controversial whether surgical management is even an option for patients with DPS". The deep transversus perinei (DTP) ligaments are the suspensory ligaments of the perineal body (PB). DTP are approximately 4 cm long. They attach behind the upper 2/3 and lower 1/3 of the descending ramus. If, at childbirth, the PB is overstretched and displaced laterally and inferiorly, the DTP lengthens. DPS is described as descent of the anus on straining, typically 3-4 cm below a line drawn from the coccyx to the lower end of the symphysis. DPS is associated with obstructed and often, assisted defecation, with increased bulging of the perineum with straining descent of the anus on straining. The surgical methodology begins as a standard PB repair which dissects the rectum from the vagina and PB and approximates the displaced components of the PB. We added an additional step: identifying the DTPs, shortening and reinforcing them with the Tissue Fixation System (TFS) minisling or No. 2 polyester sutures. High cure rates for obstructed defecation were achieved with the TFS minisling, and initial results using No. 2 polyester sutures are favourable. The key messages from both operations is DPS is caused by stretching and elongation of DPS ligaments, and these are surgically repairable.

Chronic pelvic pain of "unknown origin" in the female.

The remit of this review is confined to the experimental scientific works and surgeries based on the Integral Theory Paradigm (ITP). Chronic pelvic pain (CPP) is a major societal problem which is said to occur in up to 20% of women. The pathogenesis of CPP of "unknown origin" is said to be unknown and CPP is said to be incurable. According to the ITP, however, CPP is said to be mainly caused by the inability of loose or weak uterosacral ligaments (USLs) to mechanically support visceral nerve plexuses (VPs), T11-L2 and S2-4. These fire off de novo impulses, interpreted by the cortex as pain coming from the end organs. CPP, when it occurs simultaneously in multiple pelvic sites, is associated with uterine/apical prolapse (often minimal) and bladder symptoms such as overactive bladder (OAB), nocturia, retention. This combination of symptoms was described in 1993 as the "posterior fornix syndrome" (PFS). As such, CPP when associated with the PFS, is potentially curable by surgical repair of USLs. However, patients with CPP generally complain only of one symptom, CPP. This is known as the "Pescatori iceberg" effect. Other PFS symptoms are "under the surface" and must be sought out by direct questioning. The diagnostic algorithm is helpful in locating other associated symptoms. Definitive diagnosis of CPP, caused by USL laxity, is immediate alleviation of pain by mechanical support of USLs by using the speculum test or by tampons in the posterior fornix. Treatment of CPP can be non-surgical, by strengthening USLs by squatting exercises, supporting USLs mechanically with tampons or USL surgery. Coexisting bladder symptoms are (variously) improved or cured. URL for CPP https://www.pelviperineology.org/volume/36/issue/3.

Impaired Semen Quality in Patients with Chronic Prostatitis.

Background/Objectives: Chronic prostatitis/chronic pelvic pain syndrome CP/CPPS is a rather common condition and in recent years many studies have shown contradictory results regarding its impact on semen quality. This prospective cohort study set out to investigate how CP/CPPS affected the parameters of semen in a prospective cohort of patients compared with the WHO 2021 reference group. Methods: From 2013 to 2022, a total of 1071 patients with suspicion of CP/CPPS received a comprehensive andrological examination. Complete semen analysis was carried out in compliance with WHO 2010 guidelines, comparing every study population semen variable to the WHO 2021 reference group (n~3500). Results: All evaluated semen parameters had median values that fell within a normal range. Nonetheless, approximately 25% of patients had values for each semen variable that were lower than the WHO reference group's fifth percentile. In particular, bacteriospermia was associated with a negative impact on semen volume. Conclusions: This is the largest study that compares all standard semen parameters in patients suffering from CP/CPPS to WHO 2021 reference values. It provides evidence of an impairment of conventional semen parameters.

Therapeutic strategies for uncomplicated cystitis in women.

Uncomplicated cystitis is affecting many women of all ages and has a great impact on the quality of life, especially in women suffering from recurrent, uncomplicated cystitis. By far the most frequent uropathogen, E. coli, may have acquired increasing resistance against a variety of oral antibiotics, which may differ between countries and regions. Therefore, local resistance data are important to be considered. On the other hand, non-antibiotic therapy has also become an option which should be discussed and offered to the patient. In patients suffering from recurrent uncomplicated cystitis, individual risk factors and possible behavioral changes should first be taken into account. Non-antimicrobial prophylactic strategies shown to be successful in well-designed clinical studies are the next options. Long term antibiotic prophylaxis, however, should only be considered as a last option. For some of those patients self-diagnosis and self-treatment may be suitable, e.g. by using a recognized questionnaire.

Systematic Review and Meta-Analysis Provide no Guidance on Management of Asymptomatic Bacteriuria within the First Year after Kidney Transplantation.

(1) Background: Urinary tract infections (UTIs) are among the most frequent complications in kidney transplant (KT) recipients. Asymptomatic bacteriuria (ASB) may be a risk factor for UTIs and graft rejection. We aimed to evaluate available evidence regarding the benefit of screening and treatment of ASB within the first year after KT. (2) Evidence acquisition: A systematic literature search was conducted in MEDLINE, the Cochrane Library CENTRAL and Embase. Inclusion criteria were manuscripts in English addressing the management of ASB after KT. The PICO questions concerned Patients (adults receiving a KT), Intervention (screening, diagnosis and treatment of ASB), Control (screening and no antibiotic treatment) and Outcome (UTIs, sepsis, kidney failure and death). (3) Evidence synthesis: The systematic review identified 151 studies, and 16 full-text articles were evaluated. Seven were excluded because they did not evaluate the effect of treatment of ASB. There was no evidence for a higher incidence of lower UTIs, acute pyelonephritis, graft loss, or mortality in patients not treated with antibiotics for ASB. Analysis of comparative non-randomized and observational studies did not provide supplementary evidence to guide clinical recommendations. We believe this lack of evidence is due to confounding risk factors that are not being considered in the stratification of study patients.

European Association of Urology Guidelines on Urological Infections: Summary of the 2024 Guidelines.

BACKGROUND AND OBJECTIVE: Urological infections significantly impact the wellbeing and quality of life of individuals owing to their widespread occurrence and diverse clinical manifestations. The objective of the guidelines panel was to provide evidence-based guidance on the diagnosis, treatment, and prevention of urinary tract infections (UTIs) and male accessory-gland infections, while addressing crucial public health aspects related to infection control and antimicrobial stewardship. METHODS: For the 2024 guidelines on urological infections, new and relevant evidence was identified, collated, and appraised via a structured assessment of the literature. Databases searched included Medline, EMBASE, and the Cochrane Libraries. Recommendations within the guidelines were developed by the panel to prioritise clinically important care decisions. The strength of each recommendation was determined according to a balance between desirable and undesirable consequences of alternative management strategies, the quality of the evidence (including the certainty of estimates), and the nature and variability of patient values and preferences. KEY FINDINGS AND LIMITATIONS: Key recommendations emphasise the importance of a thorough medical history and physical examination for patients with urological infections. The guidelines stress the role of antimicrobial stewardship to combat the rising threat of antimicrobial resistance, providing recommendations for antibiotic selection, dosing, and duration on the basis of the latest evidence. CONCLUSIONS AND CLINICAL IMPLICATIONS: This overview of the 2024 EAU guidelines offers valuable insights into managing urological infections and are designed for effective integration into clinical practice. PATIENT SUMMARY: The European Association of Urology has issued an updated guideline on urological infections. The guidelines provide recommendations for diagnosis, treatment, and prevention, with a particular focus on minimising antibiotic use because of the increasing global threat of antimicrobial resistance.

Urosepsis 30-day mortality, morbidity, and their risk factors: SERPENS study, a prospective, observational multi-center study.

PURPOSE: To provide a descriptive report of mortality and morbidity in the first 30 days of diagnosis of urosepsis. Secondary aim is to identify risk factors of unfavourable outcomes. METHODS: Prospective observational multicentre cohort study conducted from September 2014 to November 2018 in European hospitals. Adult patients (≥ 18 years) diagnosed with acute urosepsis according to Sepsis-2 criteria with confirmed microbiological infection were included. Outcomes were classified in one of four health states: death, multiple organ failure, single organ failure, and recovery at day 30 from onset of urosepsis. Descriptive statistics and ordinal logistic regression analysis was performed. RESULTS: Three hundred and fifty four patients were recruited, and 30-day mortality rate was 2.8%, rising to 4.6% for severe sepsis. All patients who died had a SOFA score of ≥ 2 at diagnosis. Upon initial diagnosis, 79% (n = 281) of patients presented with OF. Within 30 days, an additional 5% developed OF, resulting in a total of 84% affected. Charlson score (OR 1.14 CI 1.01-1.28), patients with respiratory failure at baseline (OR 2.35, CI 1.32-4.21), ICU admission within the past 12 months (OR 2.05, CI 1.00-4.19), obstruction causative of urosepsis (OR 1.76, CI 1.02-3.05), urosepsis with multi-drug-resistant(MDR) pathogens (OR 2.01, CI 1.15-3.53), and SOFA baseline score ≥ 2 (OR 2.74, CI 1.49-5.07) are significantly associated with day 30 outcomes (OF and death). CONCLUSIONS: Impact of comorbidities and MDR pathogens on outcomes highlights the existence of a distinct group of patients who are prone to mortality and morbidity. These findings underscore the need for the development of pragmatic classifications to better assess the severity of UTIs and guide management strategies. STUDY REGISTRATION: Clinicaltrials.gov registration number NCT02380170.

[Urosepsis: pathophysiology, diagnosis, and management-an update]. / Urosepsis: Pathophysiologie, Diagnose und Management ­ ein Update.

Urinary tract infections vary widely in their clinical spectrum, ranging from uncomplicated cystitis to septic shock. Urosepsis accounts for 9-31% of all cases of septicemia and is often associated with nosocomial infections. A major risk factor for urosepsis is the presence of obstructive uropathy, caused by conditions such as urolithiasis, tumors, or strictures. The severity and course of urosepsis depend on both the virulence of the pathogen and the patient's specific immune response. Prompt therapy, including antimicrobial treatment and eradication of the infection source, along with supportive measures for circulatory and respiratory stabilization, and adjunctive therapies such as hemodialysis and glucocorticoid therapy, is crucial. Due to demographic changes, an increase in cases of urosepsis is expected-thus, it is of utmost importance for urologists to be familiar with targeted diagnostics and effective treatment.

[Priapism]. / Priapismus.

Priapism is defined as penile erection lasting more than four hours that is unrelated to sexual arousal. Priapism is classified based on the oxygenation of the penile tissue into ischemic and non-ischemic subtypes. As the most common form, ischemic priapism is usually associated with pain and carries a significant risk of permanent loss of erectile function; thus, rapid intervention is necessary. Initial therapy consists of corporal aspiration and injection of sympathomimetic agents. If detumescence is not achieved, a cavernosal shunt is necessary. Non-ischemic priapism is less common than the ischemic type and is usually the result of perineal trauma. In this subtype, there is usually no pain and treatment is initially conservative. Recurrent (stuttering) priapism is a variant of the ischemic subtype, but is self-limiting and usually occurs during sleep with a duration of less than three to four hours. In the case of prolonged erection, therapy is analogous to that of the ischemic subtype.

The oxytocin antagonist cligosiban reduces human prostate contractility: Implications for the treatment of benign prostatic hyperplasia.

BACKGROUND AND PURPOSE: With increasing life expectancy, benign prostatic hyperplasia (BPH) consequently affects more ageing men, illustrating the urgent need for advancements in BPH therapy. One emerging possibility may be the use of oxytocin antagonists to relax smooth muscle cells in the prostate, similar to the currently used (although often associated with side effects) α1-adrenoceptor blockers. EXPERIMENTAL APPROACH: For the first time we used live-imaging, combined with a novel image analysis method, to investigate the multidirectional contractions of the human prostate and determine their changes in response to oxytocin and the oxytocin antagonists atosiban and cligosiban. Human prostate samples were obtained and compared from patients undergoing prostatectomy due to prostate cancer as well as from patients with transurethral resection of prostate tissue due to severe BPH. KEY RESULTS: The two cohorts of tissue samples showed spontaneous multidirectional contractions, which significantly increased after the addition of oxytocin. Different to atosiban, which showed ambiguous effects of short duration, only long-acting cligosiban reliably prevented, as well as counteracted, any contractile oxytocin effect. Furthermore, cligosiban visibly reduced not only oxytocin-induced contractions, but also showed intrinsic activity to relax prostatic tissue. CONCLUSION AND IMPLICATIONS: Thus, the oxytocin antagonist cligosiban could be an interesting candidate in the search for novel BPH treatment options.

On the relationship between various anticoagulants and robot-assisted radical prostatectomy: a single-surgeon serial analysis.

Prostate cancer patients often have other health conditions and take anticoagulants. It was believed that surgery under anticoagulants could worsen surgical results. This study aims to explore the safety of robot-assisted prostatectomy in anticoagulated patients, without any exclusion criteria. The study included 500 patients who underwent RARP by a single surgeon between April 2019 and August 2022. Patients were divided into two groups: Group 1, consisting of 376 men (75.2%), did not receive any anticoagulation, while Group 2, with 124 patients (24.8%), received different forms of anticoagulation. Then, the anticoagulation group was divided into 4 subgroups according to their definite anticoagulation: the aspirin 15.6%, new oral anticoagulants (NOAC) 5.4%, Vitamin K antagonist (VKA) 2%, and dual-antiplatelet therapy (DAPT) 1.8% subgroup. Postoperative complications and readmission rates were compared between the two study groups and subgroups. Patients in the combined group 2 were older and they also carried more comorbidities compared to men in group 1 (p = 0.03, p = 0.001).The study groups had similar oncological results, with 40.4% of patients having locally advanced cancers. Catheter days were longer in the anticoagulation group (4.5 vs 4 days, p = 0.001). No significant differences were observed between study groups for overall, minor, and major complications (p = 0.160, 0.100, and 0.915, respectively). In addition, readmissions were low (5.6%) and similar between the study groups (p = 0.635). Under cautious management, RARP under diverse anticoagulation regimes is safe and has comparable results to men with no medications. Further prospective studies must be conducted to confirm our findings.

Scientific Advances in Understanding the Pathogenesis, Diagnosis, and Prevention of Urinary Tract Infection in the Past 10 Years.

Urinary tract infection (UTI) is a very common disease that is accompanied by various complications in the affected person. UTI triggers diverse inflammatory reactions locally in the infected urinary bladder and kidney, causing tissue destruction and organ failure. Moreover, systemic responses in the entire body carry the risk of urosepsis with far-reaching consequences. Understanding the cell-, organ-, and systemic mechanisms in UTI are crucial for prevention, early intervention, and current therapeutic approaches. This review summarizes the scientific advances over the last 10 years concerning pathogenesis, prevention, rapid diagnosis, and new treatment approaches. We also highlight the impact of the immune system and potential new therapies to reduce progressive and recurrent UTI.