The use of Lactobacillus casei DG® prevents symptomatic episodes and reduces the antibiotic use in patients affected by chronic bacterial prostatitis: results from a phase IV study.

PURPOSE: To evaluate the efficacy of Lactobacillus paracasei CNCM I-1572 (L. casei DG®) in both prevention of symptomatic recurrences and improvement of quality of life in patients with chronic bacterial prostatitis (CBP). METHODS: Patients with CBP attending a single Urological Institution were enrolled in this phase IV study. At enrollment, all patients were treated with antibiotics in agreement with EAU guidelines and then were treated with L. casei DG® (2 capsules/day for 3 months). Clinical and microbiological analyses were carried out before (enrollment, T0) and 6 months (T2) after the treatment. Both safety and adherence to the treatment were evaluated 3 months (T1) after the enrollment. NIH Chronic Prostatitis Symptom Index (CPSI), International Prostate Symptom Score (IPSS) and Quality of Well-Being (QoL) questionnaires were used. The outcome measures were the rate of symptomatic recurrence, changes in questionnaire symptom scores and the reduction of antibiotic use. RESULTS: Eighty-four patients were included. At T2, 61 patients (72.6%) reported a clinical improvement of symptoms with a return to their clinical status before symptoms. A time dependent improvement in clinical symptoms with significant changes in NIH-CPSI, IPSS and QoL (mean difference T2 vs T0: 16.5 ± 3.58; - 11.0 ± 4.32; + 0.3 ± 0.09; p < 0.001), was reported. We recorded that L. casei DG® treatment induced a statistically significant decrease in both (p < 0.001) symptomatic recurrence [1.9/3 months vs 0.5/3 months] and antibiotic use [- 7938 UDD]. No clinically relevant adverse effects were reported. CONCLUSIONS: L. casei DG® prevents symptomatic recurrences and improves the quality of life in patients with CBP, reducing the antibiotic use.

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.

Asymptomatic bacteriuria, to screen or not to screen - and when to treat?

PURPOSE OF REVIEW: Asymptomatic bacteriuria (ABU) is a common clinical condition that often leads to unnecessary treatment. The purpose of this review is to outline and evaluate the most recent literature on the management of ABU. RECENT FINDINGS: The role of ABU management has been evaluated in several patient subgroups: healthy patients without identified risk factors, pregnant women, postmenopausal women, women with recurrent UTI, patients with diabetes, elderly institutionalized patients, patients with renal transplants, patients with indwelling catheters and prior to surgery. Available evidence only supports the need for screening and treatment of ABU in pregnant women and prior to urological procedures breaching the mucosa. In all the other conditions the treatment of ABU is not only useless but also harmful. A short course treatment in pregnant women is recommended; in patients with ABU prior to urological procedures breaching the mucosa the treatment should be given in line with antibiogram and in line with the recommendations of European Association of Urology guidelines. SUMMARY: The approach to patients with ABU has changed completely during recent years. Today, screening and treatment of ABU is recommended only in pregnant women and in all patients who are candidates for urological procedures breaching the mucosa.

Antimicrobial Prophylaxis in Robot-Assisted Laparoscopic Radical Prostatectomy: A Systematic Review.

It remains unclear whether antibiotic prophylaxis (AP) should be recommended or discouraged in robot-assisted laparoscopic radical prostatectomy (RALP) for prostate cancer (PCa). The development of microbial resistance and side effects are risks of antibiotic use. This systematic review (SR) investigates the evidence base for AP in RALP. A systematic literature search was conducted until 12 January 2023, using Embase, MEDLINE, Cochrane CENTRAL, Cochrane CDSR (via Ovid) and CINAHL for studies reporting the effect of AP on postoperative infectious complications in RALP. Of 436 screened publications, 8 studies comprising 6378 RALP procedures met the inclusion criteria. There was no evidence of a difference in the rate and severity of infective complications within 30 days after RALP surgery between different AP protocols. No studies omitted AP. For patients who received AP, the overall occurrence of postoperative infectious complications varied between 0.6% and 6.6%. The reported urinary tract infection (UTI) rates varied from 0.16% (4/2500) to 8.9% (15/169). Wound infections were reported in 0.46% (4/865) to 1.12% (1/89). Sepsis/bacteraemia and hyperpyrexia were registered in 0.1% (1/1084) and 1.6% (5/317), respectively. Infected lymphoceles (iLC) rates were 0.9% (3 of 317) in a RALP cohort that included 88.6% pelvic lymph node dissections (PLND), and 3% (26 of 865) in a RALP cohort where all patients underwent PLND. Our findings underscore that AP is being administered in RALP procedures without scientifically proven evidence. Prospective studies that apply consistent and uniform criteria for measuring infectious complications and antibiotic-related side effects are needed to ensure the comparability of results and guidance on AP in RALP.

Practice Patterns in Fournier's Gangrene in Europe and Implications for a Prospective Registry Study.

BACKGROUND: Fournier's gangrene (FG) is a life-threatening, necrotizing infection. Due to the rareness of the disease, it is challenging to plan robust prospective studies. This study aims to describe current practice patterns of FG in Europe and identify implications for planning a prospective FG registry. METHODS: Online non-validated 17-items survey among urologists treating FG in in European hospitals. Questionnaires were analyzed with LimeSurvey (LimeSurvey GmbH Hamburg, Germany). RESULTS: 229 responses from ten different European countries were submitted, and 117 (51.1%) urologists completed the questionnaire. The departments treat a mean of 4.2 (SD 3.11) patients per year. The urology department mostly takes the lead in treating FG patients (n = 113; 96.6%). The practice in FG is very heterogenic and mostly case-based all over Europe, e.g., vacuum-assisted wound closure (VAC) is mostly used (n = 50; 42.7%) as adjunct wound. The biggest challenges in FG are the short time to diagnosis and treatment, standardization and establishment of guidelines, and disease awareness. Additionally, participants stated that an international registry is an outstanding initiative, and predictive models are needed. CONCLUSIONS: There is no standard of care in the diagnosis, treatment, and long-term care of FG all over Europe. Further research could be conducted with a prospective registry.

Artificial Intelligence Can Guide Antibiotic Choice in Recurrent UTIs and Become an Important Aid to Improve Antimicrobial Stewardship.

BACKGROUND: A correct approach to recurrent urinary tract infections (rUTIs) is an important pillar of antimicrobial stewardship. We aim to define an Artificial Neural Network (ANN) for predicting the clinical efficacy of the empiric antimicrobial treatment in women with rUTIs. METHODS: We extracted clinical and microbiological data from 1043 women. We trained an ANN on 725 patients and validated it on 318. RESULTS: The ANN showed a sensitivity of 87.8% and specificity of 97.3% in predicting the clinical efficacy of empirical therapy. The previous use of fluoroquinolones (HR = 4.23; p = 0.008) and cephalosporins (HR = 2.81; p = 0.003) as well as the presence of Escherichia coli with resistance against cotrimoxazole (HR = 3.54; p = 0.001) have been identified as the most important variables affecting the ANN output decision predicting the fluoroquinolones-based therapy failure. A previous isolation of Escherichia coli with resistance against fosfomycin (HR = 2.67; p = 0.001) and amoxicillin-clavulanic acid (HR = 1.94; p = 0.001) seems to be the most influential variable affecting the output decision predicting the cephalosporins- and cotrimoxazole-based therapy failure. The previously mentioned Escherichia coli with resistance against cotrimoxazole (HR = 2.35; p < 0.001) and amoxicillin-clavulanic acid (HR = 3.41; p = 0.007) seems to be the most influential variable affecting the output decision predicting the fosfomycin-based therapy failure. CONCLUSIONS: ANNs seem to be an interesting tool to guide the antimicrobial choice in the management of rUTIs at the point of care.

Non-Antibiotic Prophylaxis for Recurrent UTIs in Neurogenic Lower Urinary Tract Dysfunction (NAPRUN): Study Protocol for a Prospective, Longitudinal Multi-Arm Observational Study.

INTRODUCTION: Patients with neurogenic lower urinary tract dysfunction (NLUTD) reliant on intermittent self-catheterization for bladder emptying are at an increased risk of recurrent urinary tract infections (rUTI). So far, the most common practice in the prevention of rUTIs is long-term low-dose antibiotic prophylaxis, phytotherapy, and immunomodulation, whereby antibiotic prophylaxis inevitably leads to the emergence of drug-resistant pathogens and difficulty in treating infections. Therefore, non-antibiotic alternatives in the prevention of rUTIs are urgently required. We aim to identify the comparative clinical effectiveness of a non-antibiotic prophylaxis regimen in the prevention of recurrent urinary tract infections in patients with neurogenic bladder dysfunction who practice intermittent self-catheterization. METHODS AND ANALYSIS: In this multi-centre, prospective longitudinal multi-arm observational study, a total of 785 patients practising intermittent self-catheterisation due to NLUTD will be included. After inclusion, non-antibiotic prophylaxis regimens will be instilled with either UroVaxom® (OM-89) standard regimen, StroVac® (bacterial lysate vaccine) standard regimen, Angocin®, D-mannose (oral dose 2 g), bladder irrigation with saline (once per day). The management protocols will be pre-defined, but the selection of the protocol will be at the clinicians' discretion. Patients will be followed for 12 months from the onset of the prophylaxis protocol. The primary outcome is to identify the incidence of breakthrough infections. The secondary outcomes are adverse events associated with the prophylaxis regimens and the severity of breakthrough infections. Other outcomes include the exploration of change in susceptibility pattern via the optional rectal and perineal swab, as well as health-related quality of life over time (HRQoL), which will be measured in a random subgroup of 30 patients. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the ethical review board of the University Medical Centre Rostock (A 2021-0238 from 28 October 2021). The results will be published in a peer-reviewed journal and presented at relevant meetings. STUDY REGISTRATION NUMBER: German Clinical Trials Register: Number DRKS00029142.

Antibiotic Resistance Patterns Among Uropathogens in Female Outpatients Affected by Uncomplicated Cystitis: Focus on Fosfomycin Trometamol.

OBJECTIVES: To report the resistance rate against fosfomycin trometamol among outpatient women with symptoms related to urinary tract infections over a 6-year period in a multicentre, cross-sectional study. METHODS: Urinary samples were collected from three high-volume laboratories from January 2015 to December 2020. The pattern of resistance to fosfomycin was analysed by using the Vitek II automated system. RESULTS: A total of 7289 urinary samples were collected and 8321 strains were analysed during the study period. The most commonly isolated uropathogen was Escherichia coli (n = 6583, 79.1%). The mean resistance rate against fosfomycin was 9.7% (range 7.1-11.3). No statistically significant difference was found between the three laboratories (P = 0.53). There was no significant increase in resistance rate during the study period. The mean resistance rate against fosfomycin was higher among extended-spectrum ß-lactamase (ESBL)-producing bacteria when compared with non-ESBL-producing strains (10.8% vs. 7.9%; P < 0.001). CONCLUSION: Uropathogens isolated from women affected by cystitis remained highly susceptible to fosfomycin. These findings confirm recommendations in international guidelines that advocate fosfomycin trometamol for empirical treatment of uncomplicated cystitis in women.

A Proposal of a New Nomogram to Predict the Need for Testosterone ReplACEment (TRACE): A Simple Tool for Everyday Clinical Practice.

International guidelines suggest to use testosterone therapy (TTh) in hypogonadal men presenting symptoms of testosterone deficiency (TD), even if there is no fixed threshold level of T at which TTh should be started. We aimed to develop and validate a nomogram named TRACE (Testosterone ReplACEment) for predicting the need of TTh in patients with "low-normal" total testosterone levels. The following nomogram variables were used: serum T level; serum LH level; BMI; state of nocturnal erections; metabolic comorbidities; and IPSS total score. The nomogram has been tested by calculating concordance probabilities, as well as assaying the calibration of predicted probability of clinical testosterone deficiency and need for TTh, together with the clinical outcome of the TTh. A cohort of 141 patients was used for the development of the nomogram, while a cohort of 123 patients attending another institution was used to externally validate and calibrate it. Sixty-four patients (45.3%) received TTh. Among them, sixty patients (93.7%) reported a significant clinical improvement after TTh. The nomogram had a concordance index of 0.83 [area under the ROC curve 0.81 (95% CI 0.71-0.83)]. In conclusion, the TRACE nomogram accurately predicted the probability of clinical impairment related to TD, and resulted in a simple and reliable method to use to select hypogonadal patients with not clearly pathological testosterone values who will benefit from TTh.

Fosfomycin trometamol and N-acetyl-L-cysteine as combined oral therapy of difficult-to-treat chronic bacterial prostatitis: Results of a pilot study.

This paper presents the results of a pilot study of difficult-to-treat patients (exhibiting several previous treatment failures or detection of extended-spectrum beta-lactamase [ESBL] strains) with chronic bacterial prostatitis (CBP) who underwent treatment with fosfomycin trometamol (FT) and N-acetyl-L-cysteine (NAC). Twenty-eight patients with clinically- and microbiologically-confirmed CBP who attended a single urological institution between January 2018 and March 2019 were treated with oral administration of 3 g FT once a day for 2 days, followed by a dose of 3 g every 48 h for 2 weeks, in combination with oral administration of NAC 600 mg once a day for 2 weeks. Clinical and microbiological analyses were carried out at the time of admission (T0) and during follow-up at 1 month (T1) and 6 months (T2) after the end of treatment. Symptoms were assessed by the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and International Prostatic Symptom Score (IPSS), and quality of life was assessed by Quality of Well-Being (QoL) questionnaires. Isolated strains were Escherichia coli (23 patients), Enterococcus spp. (3 patients), and Klebsiella oxytoca (2 patients). ESBL strain was found in 19 (67.8%) patients. Microbiological eradication was documented in 21 (75%) patients at the second follow-up visit and clinical cure was achieved in 20 (71.4%) patients. Significant changes on questionnaires were recorded between baseline and follow-up visits. Fifteen of 19 patients (78.9%) with ESBL strains were cured. No significant side effects were reported. FT in combination with NAC is a promising alternative therapy in difficult-to-treat CBP patients.

[Hormone treatment of prostate cancer in Norway]. / Hormonbehandling av prostatakreft i Norge.

BACKGROUND: The aim of our study was to determine the association between hormone treatment of prostate cancer and survival for those affected. MATERIAL AND METHODS: Data were retrieved from several official Norwegian registries on hormone treatment, cancer in various stages, and the use of radical prostatectomies and external beam radiation therapy with curative intent. RESULTS: The number of patients treated with hormones has risen 10-fold during the last decade. GnRH analogues and/or bicalutamide are used to treat more than 90 % of patients. The counties that use radical prostatectomy most frequently also have the most pronounced increase in hormone treatment and the increases in parallel over time. A cohort of Norwegian men will have a net loss of 1025 patient-years over a 10-year period if the number of patient-years gained and lost is calculated with current treatment practice and based on the number of radical treated and hormone-treated patients and expected survival with prostate cancer in Norway and expectations according to randomised, controlled studies on radical treatment and hormone treatment in general. INTERPRETATION: There are reasons to discuss whether the extent of hormone-treatment and radical treatment should be reduced. A reduction would be most easily achieved by reducing wild-screening of PSA in serum.