networks-based classification. The workflow was benchmarked on 21 clinical isolates from four WHO priority pathogens that were antibiotic susceptibility tested, and their AMR profile was determined by WGS. "Accurate classification based on the gram staining was 100% recall for gram- negative and 83.4% for gram-positive, species identification was 98.6%, and assessment of resistant/ susceptible type was 96.4%." The proposed optical assay was in good agreement with the WGS characterisation. Accurate classification based on the gram staining was 100% recall for gram-negative and 83.4% for gram-positive, species identification was 98.6%, and assessment of resistant/susceptible type was 96.4%. At the individual strain level there was 100% sensitivity in predicting 19 out of the 21 strains, with an overall accuracy of 95.45%. The results from this proof-of-concept study demonstrate the potential of the QPM assay as a rapid and first-stage tool for species and strain-level classification, and for detecting the presence or absence of AMR, which WGS can follow-up for confirmation. Overall, a combined workflow with QPM and WGS complemented with deep learning data analyses could, in the future, be transformative for detecting and identifying pathogens and characterisation of the AMR profile and antibiotic susceptibility. The present paper demonstrates that use of label-free optical assay with whole-genome sequencing complemented with deep learning data analyses is a method of bacterial identification that warrants further studies as it has minimum dependencies on the still time-consuming approach of bacterial culturing. Source: Highly sensitive quantitative phase microscopy and deep learning aided with whole genome sequencing for rapid detection of infection and antimicrobial resistance. Ahmad A, Hettiarachchi R, Khezri A, Singh Ahluwalia B, Wadduwage DN and Ahmad R. Front. Microbiol. 2023;14:1154620. doi: 10.3389/ fmicb.2023.1154620 Which men with metastatic hormone-sensitive prostate cancer should be offered triple therapy? The treatment recommendations for metastatic hormone-sensitive prostate cancer (mHSPC) have changed dramatically in the last decade. New treatment combinations have shown compelling overall survival (OS) benefits, leading to a treatment intensification at this stage of the disease. Last year, the results from PEACE-1 and ARASENS were published and guideline recommendations were changed. It is now recommended in the EAU Guidelines to offer docetaxel in combination with androgen deprivation therapy (ADT) plus an androgen pathway inhibitor (API) to men with mHSPC fit for docetaxel. PEACE-1 and ARASENS were randomised clinical trials that investigated the addition of an API, abiraterone plus prednisone (AAP) and darolutamide respectively, to a backbone of ADT + docetaxel. The addition of an API provided an OS benefit over placebo. While the addition of an API to ADT + docetaxel has been shown to improve OS, it has not formally been shown if the addition of docetaxel to ADT + API infers similar OS benefits.
systemic treatment options for mHSPC across patient subgroups in a “living” systematic review and network meta-analysis. The method of a living review is unique and allows for continuous evidence updates in part through advanced computer programming and artificial intelligence. The authors had a particular interest in comparing triplet therapy with an API + ADT. In all, 10 randomised clinical trials comprising 11,043 patients across nine unique treatment options were assessed. The triple therapy regimens were ranked the potentially most efficacious treatments for mHSPC. The patients that seemed to benefit the most were those with synchronous and high-volume mHSPC. Interestingly, the triple therapies were associated with better OS when compared with ADT + docetaxel, but not when compared with an API + ADT, i.e. ADT + enzalutamide, ADT + apalutamide or ADT + AAP. At the same time, the triple therapies were associated with a higher risk of Grade 3 and above adverse events. "Triple therapies were associated with better OS when compared with ADT + docetaxel, but not when compared with an API + ADT." The authors conclude that triple therapy may be preferred for men with high-volume synchronous mHSPC while omitting docetaxel may be preferred for metachronous low volume mHSPC. For those with high-volume metachronous disease or low-volume synchronous mHSPC an individualised risk-based approach must be taken. This study highlights the importance of carefully selecting the right patients for triple therapy and considering the benefits versus potential harms of adding docetaxel to an API doublet with ADT. The extend of metastatic disease and time of metastatic presentation are some of the variables that may guide treatment selection. However, further efforts to individualise treatment and better understand the heterogeneity of mHSPC are warranted. Source: First-line Systemic Treatment Options for Metastatic Castration- Sensitive Prostate Cancer: A Living Systematic Review and Network Meta- analysis. Riaz IB, Naqvi SAA, He H, et al. JAMA Oncol. 2023 Mar 2:e227762. doi: 10.1001/jamaoncol.2022.7762. The efficacy of standard urotherapy in the treatment of nocturnal enuresis in children is not well-supported by the current evidence Initial conservative management of primary nocturnal enuresis (PNE) is about information and demystification. PNE involves mainly informing the family about urinary tract dysfunction and spontaneous resolution; lifestyle, and dietary changes (fluid intake and diet for constipation); registration of symptoms and voiding habits; and support and encouragement in children. PNE is usually the initial preferred treatment modality for many physicians and also other health personnel as it is conservative approach. There may be inconveniencies to employ them properly as it requires some strict life style changes such as fluid intake restriction. The study includes a systematic literature search to look at the impact of this standard approach. Out of 2,476 studies 22 randomised controlled trial (RCT) studies were included to the study. Most other studies scored poorly in terms of evidence quality as studies combined several urotherapy interventions and studied different study populations. Twenty-two RCTs reported 0 to 92% of children being dry after standard urotherapy treatment. Three RCTs with the highest quality scores individualise and optimise drinking, voiding during the day,
Prof. Serdar Tekgül Section Editor Ankara (TR)
Prof. Truls Erik Bjerklund Johansen Section editor Oslo (NO)
serdartekgul@ gmail.com
tebj@medisin.uio.no
and practising optimal toilet posture. These trials reported that few children experienced complete resolution of nocturnal enuresis (5 to 33%). "Until better evidence becomes available, considering other treatment modalities such as medical treatment or alarm treatment, may save time for children who are suffering from nocturnal enuresis." There is insufficient evidence for offering standard urotherapy to children with PNE as first-line treatment modality. Until better evidence becomes available, considering other treatment modalities such as medical treatment or alarm treatment, may save time for children who are suffering from nocturnal enuresis. The available literature in the field of standard urotherapy concerning the treatment of children with PNE lacks high level of evidence due to heterogeneity of the study populations and interventions. The limited number of high-quality studies does not really support the use of standard urotherapy for PNE. Due to the presence of insufficient evidence for recommending standard urotherapy to children with PNE as a first-line treatment modality, other treatment options such as medical treatment or alarm treatment should be considered earlier especially for the patient group who suffers significantly. Source: The efficacy of standard urotherapy in the treatment of nocturnal enuresis in children: A systematic review. Cecilie Siggaard Jørgensen, Konstantinos Kamperis, Johan Vande Walle, Søren Rittig, Ann Raes, Lien Dossche. Journal of Pediatric Urology, Volume 19, Issue 2, 2023, Pages 163-172 Oral tebipenem pivoxil hydrobromide in complicated urinary tract infection There is a need for oral antibiotic agents that are effective against multidrug-resistant gram-negative uropathogens. Tebipenem pivoxil hydrobromide is an orally bioavailable carbapenem with activity against uropathogenic Enterobacterales, including extended-spectrum beta-lactamase- producing and fluoroquinolone-resistant strains. In this phase 3, international, double-blind, double-dummy trial, the investigators evaluated the efficacy and safety of orally administered tebipenem pivoxil hydrobromide as compared with intravenous ertapenem in patients with complicated urinary tract infection or acute pyelonephritis. Patients were randomly assigned, in a 1:1 ratio, to receive oral tebipenem pivoxil hydrobromide (at a dose of 600 mg every 8 hours) or intravenous ertapenem (at a dose of 1 g every 24 hrs) for 7- 10 days (or up to 14 days in patients with bacteraemia). The primary efficacy end point was overall response (a composite of clinical cure and favourable microbiologic response) at a test-of-cure visit
Prof. Oliver Reich Section editor Munich (DE)
oliver.reich@ klinikum-muenchen.de
Prof. Oliver Hakenberg Section Editor Rostock (DE)
Oliver.Hakenberg@ med.uni-rostock.de
(on day 19, within a ±2-day window) in the microbiologic intention-to-treat population. The noninferiority margin was 12.5%. "…oral tebipenem pivoxil hydrobromide was noninferior to intravenous ertapenem in the treatment of complicated urinary tract infection…" A total of 1372 hospitalised adult patients were enrolled; 868 patients (63.3%) were included in the microbiologic intention-to- treat population (50.8% of whom had complicated urinary tract infections and 49.2% of whom had pyelonephritis). An overall response was seen in 264 of 449 patients (58.8%) who received tebipenem pivoxil hydrobromide, as compared with 258 of 419 patients (61.6%) who received ertapenem (weighted difference, -3.3 percentage points; 95% confidence interval [CI], -9.7 to 3.2). Clinical cure at the test-of- cure visit was observed in 93.1% of the patients in the microbiologic intention-to-treat population who received tebipenem pivoxil hydrobromide and 93.6% of patients who received ertapenem (weighted difference, -0.6 percentage point; 95% CI, -4.0 to 2.8); the majority of patients with microbiologic response failures at the test-of-cure visit were asymptomatic patients with recurrent bacteriuria. Adverse events were observed in 25.7% of patients who received tebipenem pivoxil hydrobromide and in 25.6% of patients who received ertapenem; the most common adverse events were mild diarrhoea and headache. The authors conclude that oral tebipenem pivoxil hydrobromide was noninferior to intravenous ertapenem in the treatment of complicated urinary tract infection and acute pyelonephritis and had a similar safety profile. (Funded by Spero Therapeutics and the Department of Health and Human Services; ADAPT-PO ClinicalTrials.gov number, NCT03788967). Source: Oral Tebipenem Pivoxil Hydrobromide in Complicated Urinary Tract Infection. Eckburg PB, Muir L, Critchley IA, Walpole S, Kwak H, Phelan A-M, Moore G, Jain A, Keutzer T, Dane A, Melnick D, Talley AK. N Engl J Med 2022 7;386(14):1327-1338. doi: 10.1056/NEJMoa2105462
Riaz et al. sought to compare the current
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