Expert Review of Anti-infective Therapy最新文献

{"title":"Febrile neutropenia management in high-risk neutropenic patients: a narrative review on antibiotic prophylaxis and empirical treatment.","authors":"Cemre Boşnak, Murat Akova","doi":"10.1080/14787210.2025.2487149","DOIUrl":"10.1080/14787210.2025.2487149","url":null,"abstract":"<p><strong>Introduction: </strong>Although febrile neutropenia (FN) remains a major cause of morbidity and mortality in patients with hematologic malignancies and hematopoietic stem cell transplant (HSCT) recipients, the increasing prevalence of antimicrobial resistance necessitates a reassessment of antibiotic prophylaxis and treatment strategies.</p><p><strong>Areas covered: </strong>This review explores the prophylactic and therapeutic use of antibiotics in FN management, with a particular focus on patients with hematologic malignancies - particularly acute leukemia - and HSCT recipients.</p><p><strong>Expert opinion: </strong>Challenges in FN management, including antibiotic prophylaxis and treatment optimization, remain due to the complexity of the condition. Pathogens with emerging antibacterial resistance cause significant concern in the management of patients. Particularly due to selection potential of resistant Gram-negative bacteria (GNB), fluoroquinolones (FQs) have become less attractive agents for prophylaxis. Whereas, emerging data may help to revitalize long-abandoned aminoglycoside containing combination therapies particularly in high-risk patients with presumed sepsis. With only a few agents available for highly resistant bacteria alternative treatment strategies including pharmacokinetic/pharmacodynamic (PK/PD) concerning antibiotic applications may be warranted. Carefully designed, randomized, controlled trials providing large scale data which then can be analyzed with emerging artificial intelligence (AI) technologies are needed. The results from such trials may allow a better, data-driven approaches for management of FN.</p>","PeriodicalId":12213,"journal":{"name":"Expert Review of Anti-infective Therapy","volume":" ","pages":"1-15"},"PeriodicalIF":4.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adding collagen, propolis plus quercetin, bacillus coagulans, hyaluronic acid and chondroitin sulphate to D-mannose avoids symptoms and prevents recurrence in women with recurrent urinary tract infections: a single-blind randomized controlled trial.","authors":"Gaetano Riemma, Davide Vinci, Marco La Verde, Florindo Mario Caniglia, Gaetano Scalzone, Marco Torella","doi":"10.1080/14787210.2025.2487162","DOIUrl":"10.1080/14787210.2025.2487162","url":null,"abstract":"<p><strong>Background: </strong>To evaluate the efficacy of a new D-mannose dietary supplement containing D-mannose, Propolis-Quercetin, Bacillus Coagulans, Hyaluronic Acid and Chondroitin Sulfate with fosfomycin in reducing rUTI episodes and improving quality of life.</p><p><strong>Research design and methods: </strong>Single-blind, randomized controlled trial conducted at tertiary-care hospital in Italy. Women aged 21-65 with a history of rUTIs were randomized into three groups: fosfomycin, the dietary supplement, and a combination of both treatments. Primary outcome was frequency of rUTI episodes per month.</p><p><strong>Results: </strong>Combination therapy demonstrated greatest reduction in rUTI episodes per month at 12 months compared to fosfomycin or supplement monotherapy (0.23 ± 0.37 vs 0.58 ± 0.67 and 1.12 ± 0.96 for fosfomycin and supplement monotherapy respectively; <i>p</i> < 0.05) and to supplement monotherapy at 6 months (0.69 ± 1.03 vs 1.43 ± 1.33; <i>p</i> < 0.05), with significant improvement of ICIQ-FLUTS domains compared to other groups at 12 months (<i>p</i> < 0.05). Combination therapy had lower number of women matching rUTI criteria (55.32% vs 76.47% and 84%; <i>p</i> < 0.05) and symptoms remission at 12 months (89.36% vs 56.86% and 20%; <i>p</i> < 0.001).</p><p><strong>Conclusions: </strong>Combining fosfomycin and an integrated D-mannose supplement for managing rUTIs offers a potential reduction in antibiotic reliance. Further large-scale studies are recommended to confirm these findings.</p><p><strong>Trial registration: </strong>The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT06659016).</p>","PeriodicalId":12213,"journal":{"name":"Expert Review of Anti-infective Therapy","volume":" ","pages":"1-8"},"PeriodicalIF":4.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective antimicrobial therapies needed for treatment of severe infections in African newborns.","authors":"Pui-Ying Iroh Tam, Adrie Bekker, Julia Anna Bielicki, Olufunke Bolaji, Gwendoline Chimhini, Ziyaad Dangor, Felicity Fitzgerald, Nelesh Govender, Sandi Holgate, Gugulabatembunamahlubi Tj Kali, Uduak Okomo, Tochi Okwor, Charlene Rodrigues, Sithembiso Velaphi, Andrew Whitelaw, Angela Dramowski","doi":"10.1080/14787210.2025.2484281","DOIUrl":"10.1080/14787210.2025.2484281","url":null,"abstract":"","PeriodicalId":12213,"journal":{"name":"Expert Review of Anti-infective Therapy","volume":" ","pages":"1-4"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Twenty-five years of palivizumab: a global historic review of its impact on the burden of respiratory syncytial virus disease in children.","authors":"Xavier Carbonell-Estrany, Eric A F Simões, Louis Bont, Paolo Manzoni, Heather J Zar, Anne Greenough, Octavio Ramilo, Renato Stein, Barbara Law, Asuncion Mejias, Manuel Sanchez Luna, Paul A Checchia, Leonard Krilov, Marcello Lanari, Ron Dagan, Brigitte Fauroux, Bernhard Resch, Terho Heikkinen, Joseph B Domachowske, Joanne G Wildenbeest, Federico Martinon-Torres, Richard Thwaites, Merih Cetinkaya, Adel S Alharbi, Carlos E Rodriguez-Martinez, Daniel E Noyola, Asiah Kassim, Satoshi Kusuda, Ji-Man Kang, Barry Rodgers-Gray, Anna Platonova, Fungwe Jah, Bosco Paes","doi":"10.1080/14787210.2025.2481908","DOIUrl":"10.1080/14787210.2025.2481908","url":null,"abstract":"<p><strong>Introduction: </strong>Respiratory syncytial virus (RSV) causes significant morbidity and mortality in young children. For 25 years, palivizumab has been the only effective pharmaceutical RSV preventive.</p><p><strong>Areas covered: </strong>We summarize the development and a quarter-century of real-world evidence with palivizumab. We highlight its positive impact on the burden of RSV in high-risk children. Based on lessons learnt from its implementation, we suggest strategies for effective and equitable deployment of newer RSV preventives.</p><p><strong>Expert opinion: </strong>Following failure of the formalin-inactivated RSV vaccine in 1967, RSV intravenous immunoglobulin was approved in 1996 after three decades' research. Subsequently, palivizumab emerged as the most effective and safe RSV preventive, demonstrated by the IMpact trial, and was licensed in 1998 in the United States. Over the last 25 years, the benefits of palivizumab have been firmly established through a wealth of evidence, predominantly from high-income countries (HICs). To achieve a global impact with the newer RSV preventives, evidenced-based universal guidelines must be developed and endorsed by regulatory authorities and relevant scientific societies. Independent economic evaluations should incorporate all RSV-associated healthcare costs, reduction of long-term respiratory sequelae, and standardized outcomes. Most importantly, equity in product availability and implementation, particularly in low- and middle-income countries (LMICs) is essential.</p>","PeriodicalId":12213,"journal":{"name":"Expert Review of Anti-infective Therapy","volume":" ","pages":"1-20"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of methicillin-resistant <i>staphylococcus aureus</i> bloodstream infections: a comprehensive narrative review of available evidence focusing on current controversies and the challenges ahead.","authors":"Alberto Enrico Maraolo, Milo Gatti, Luigi Principe, Andrea Marino, Giuseppe Pipitone, Gennaro De Pascale, Giancarlo Ceccarelli","doi":"10.1080/14787210.2025.2487163","DOIUrl":"https://doi.org/10.1080/14787210.2025.2487163","url":null,"abstract":"<p><strong>Introduction: </strong>Bloodstream infections (BSIs) caused by <i>Staphylococcus aureus</i> are common worldwide, representing one of the most relevant issues in clinical infectious diseases practice. In particular, BSIs by methicillin-resistant <i>S. aureus</i> (MRSA-BSI) are still today a challenge since mortality burden remains elevated although decades of research.</p><p><strong>Areas covered: </strong>The following topics regarding MRSA-BSI were reviewed and discussed by resorting to best available evidence retrieved from PubMed/MEDLINE up to October 2024: i) epidemiology; ii) microbiology; iii) classification, with a focus on complicated and not complicated forms; iv) the structured approach to the patient; v) pharmacokinetics and pharmacodynamics of the main antimicrobial options; vi) controversies regarding the best therapeutic approach.</p><p><strong>Expert opinion: </strong>Despite ongoing efforts to better stratify and manage MRSA-BSI, there is no universally accepted classification system accurately distinguishing between uncomplicated/low risk and complicated/high risk forms. Biomarkers such as interleukin(IL)-10 hold promise in order to enable a more precise stratification, premise for an appropriate treatment plan. There is a theoretical rationale for implementing a combination therapy including a beta-lactam agent upfront, especially for patients considered at higher risk of unfavorable outcomes, but further data are necessary, and the same applies to newer adjuvants. Novel microbiological techniques may help in guiding antimicrobial duration.</p>","PeriodicalId":12213,"journal":{"name":"Expert Review of Anti-infective Therapy","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of chronic hepatitis C infection: strategies to address poor therapy adherence.","authors":"Robert Flisiak, Piotr Rzymski, Marta Flisiak-Jackiewicz, Michał Brzdęk, Dorota Zarębska-Michaluk","doi":"10.1080/14787210.2025.2486353","DOIUrl":"https://doi.org/10.1080/14787210.2025.2486353","url":null,"abstract":"<p><strong>Introduction: </strong>Non-adherence to any therapy may be related to skipping drug doses, discontinuation of therapy, or loss of follow-up. It leads to the ineffectiveness of treatment, which is associated with obvious individual health losses, significant social and financial costs, and, in the case of infectious diseases, epidemiological consequences resulting from the possibility of further spread of infection.</p><p><strong>Areas covered: </strong>This review article analyses the causes and effects of non-adherence to treatment in patients infected with the hepatitis C virus (HCV). It also presents strategies to reduce the risk of non-adherence, which can be implemented by simplifying the treatment process, improving the flow of information between the doctor and the patient, as well as improving patients' knowledge about hepatitis C infection, and facilitating the understanding of the risks associated with non-adherence.</p><p><strong>Expert opinion: </strong>Since the treatment of HCV infections is highly effective in almost all patients who complete medication, no new drugs are to be expected in the coming years. Therefore, the primary attention in the global elimination of HCV will be focused on screening programs, improving the availability of drugs, and reducing the risk of non-adherence.</p>","PeriodicalId":12213,"journal":{"name":"Expert Review of Anti-infective Therapy","volume":" ","pages":"1-9"},"PeriodicalIF":4.2,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of bacterial spectrum and construction of a predictive model for postoperative sepsis in patients with upper urinary calculi and positive urinary cultures.","authors":"Yizhou Wang, Meng Gao, Minghui Liu, Jinbo Chen, Zewu Zhu","doi":"10.1080/14787210.2025.2484285","DOIUrl":"10.1080/14787210.2025.2484285","url":null,"abstract":"<p><strong>Background: </strong>To analyze bacterial profiles, antibiotic resistance, and urosepsis risk factors in urine culture-positive (UC+) patients post-endoscopic lithotripsy.</p><p><strong>Research design and method: </strong>Retrospectively, 806 UC+ patients (2016.3-2021.3) were stratified into urosepsis/non-urosepsis groups per Sepsis-3 criteria.</p><p><strong>Results: </strong>Among 845 isolates (56 species), <i>Escherichia coli</i> dominated (46.8%), followed by <i>Enterococcus faecalis</i> (8.8%). Gram-negative bacteria exhibited high resistance to ampicillin, cefazolin, and cefuroxime. Multivariate analysis identified preoperative multidrug-resistant (MDR) bacteriuria (OR = 2.15), staghorn calculi (OR = 2.23), days of preoperative antibiotics use <3 (OR = 1.87), absence of nephrostomy (OR = 2.30), and postoperative WBC > 9.8 × 10⁹/L (OR = 2.69) as independent sepsis predictors. A nomogram incorporating these factors achieved robust predictive accuracy. Preoperative antibiotic use for ≥3 days was inversely correlated with the risk of urinary sepsis as the duration of antibiotic administration increased.</p><p><strong>Conclusions: </strong>Urosepsis incidence was 13.1% post-lithotripsy. Early risk stratification, targeted infection control, and antibiotic stewardship guided by urine susceptibility testing are critical for prevention.</p>","PeriodicalId":12213,"journal":{"name":"Expert Review of Anti-infective Therapy","volume":" ","pages":"1-8"},"PeriodicalIF":4.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence and its application in clinical microbiology.","authors":"Assia Mairi, Lamia Hamza, Abdelaziz Touati","doi":"10.1080/14787210.2025.2484284","DOIUrl":"10.1080/14787210.2025.2484284","url":null,"abstract":"<p><strong>Introduction: </strong>Traditional microbiological diagnostics face challenges in pathogen identification speed and antimicrobial resistance (AMR) evaluation. Artificial intelligence (AI) offers transformative solutions, necessitating a comprehensive review of its applications, advancements, and integration challenges in clinical microbiology.</p><p><strong>Areas covered: </strong>This review examines AI-driven methodologies, including machine learning (ML), deep learning (DL), and convolutional neural networks (CNNs), for enhancing pathogen detection, AMR prediction, and diagnostic imaging. Applications in virology (e.g. COVID-19 RT-PCR optimization), parasitology (e.g. malaria detection), and bacteriology (e.g. automated colony counting) are analyzed. A literature search was conducted using PubMed, Scopus, and Web of Science (2018-2024), prioritizing peer-reviewed studies on AI's diagnostic accuracy, workflow efficiency, and clinical validation.</p><p><strong>Expert opinion: </strong>AI significantly improves diagnostic precision and operational efficiency but requires robust validation to address data heterogeneity, model interpretability, and ethical concerns. Future success hinges on interdisciplinary collaboration to develop standardized, equitable AI tools tailored for global healthcare settings. Advancing explainable AI and federated learning frameworks will be critical for bridging current implementation gaps and maximizing AI's potential in combating infectious diseases.</p>","PeriodicalId":12213,"journal":{"name":"Expert Review of Anti-infective Therapy","volume":" ","pages":"1-22"},"PeriodicalIF":4.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gram-positive infections in special populations. Expert view on the role of dalbavancin.","authors":"Beatriz Sobrino, Sonia Luque, Eneritz Velasco-Arnaiz, Rubén Lovatti González, José Luis Del Pozo","doi":"10.1080/14787210.2025.2477196","DOIUrl":"10.1080/14787210.2025.2477196","url":null,"abstract":"<p><strong>Introduction: </strong>This review considers special populations as those patients for whom Gram-positive infections are particularly challenging to treat. We examine the potential benefits of dalbavancin in these patients.</p><p><strong>Areas covered: </strong>We focus on patients with renal impairment, hepatic failure or obesity, and, also, pediatric patients, elderly patients and socially vulnerable individuals. Five independent experts conducted exhaustive literature searches on PubMed. Papers were selected for inclusion according to their relevance to the topic. For each special population, we outline the most significant characteristics for infection management, describing the challenges of the most frequent Gram-positive infections, and reviewing the potential role of dalbavancin.</p><p><strong>Expert opinion: </strong>Dalbavancin may be a valid alternative to overcome the difficulties of infection management in these populations. We hope our insights will prove useful for patient-centered care. A long half-life, evidence-based efficacy and good safety profile make dalbavancin an adequate option, particularly for patients for whom oral treatment or continued IV access may be challenging, or those for whom hospital stay is more impactful. [Figure: see text].</p>","PeriodicalId":12213,"journal":{"name":"Expert Review of Anti-infective Therapy","volume":" ","pages":"1-11"},"PeriodicalIF":4.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current access, availability and use of antibiotics in primary care among key low- and middle-income countries and the policy implications.","authors":"Zikria Saleem, Biset Asrade Mekonnen, E Sam Orubu, Md Ariful Islam, Thuy Thi Phuong Nguyen, Chukwuemeka Michael Ubaka, Deus Buma, Nga Do Thi Thuy, Yashasvi Sant, Tiyani Milta Sono, Tomasz Bochenek, Aubrey C Kalungia, Saad Abdullah, Nenad Miljković, Eugene Yeika, Loveline Lum Niba, George Akafity, Israel Abebrese Sefah, Sylvia A Opanga, Freddy Eric Kitutu, Felix Khuluza, Trust Zaranyika, Ayuska Parajuli, Omeed Darweesh, Salequl Islam, Santosh Kumar, Hellen Nabayiga, Ammar Abdulrahman Jairoun, Audrey Chigome, Olayinka Ogunleye, Joseph Fadare, Amos Massele, Aislinn Cook, Ana Golić Jelić, Isabella Piassi Dias Godói, Amani Phillip, Johanna C Meyer, Elisa Funiciello, Giulia Lorenzetti, Amanj Kurdi, Abdul Haseeb, Catrin E Moore, Stephen M Campbell, Brian Godman, Mike Sharland","doi":"10.1080/14787210.2025.2477198","DOIUrl":"https://doi.org/10.1080/14787210.2025.2477198","url":null,"abstract":"<p><strong>Introduction: </strong>Antimicrobial resistance (AMR) poses a significant threat, particularly in low- and middle-income countries (LMICs), exacerbated by inappropriate antibiotic use, access to quality antibiotics and weak antimicrobial stewardship (AMS). There is a need to review current evidence on antibiotic use, access, and AMR, in primary care across key countries.Areas covered: This narrative review analyses publications from 2018 to 2024 regarding access, availability and use of appropriate antibiotics.</p><p><strong>Expert opinion: </strong>There were very few studies focussing on a lack of access to antibiotics in primary care. However, there was considerable evidence of high rates of inappropriate antibiotic use, including Watch antibiotics, typically for minor infections, across studied countries exacerbated by patient demand. The high costs of antibiotics in a number of LMICs impacts on their use resulting in short courses and sharing of antibiotics. This can contribute to AMR alongside the use of substandard and falsified antibiotics. Overall, limited implementation of national action plans, insufficient resources, and knowledge gaps, affects sustainable development goals to provide routine access to safe, effective and appropriate antibiotics.</p><p><strong>Conclusions: </strong>There is a clear need to focus health policy on the optimal use of essential AWaRe antibiotics in primary care settings to reduce AMR in LMICs.</p>","PeriodicalId":12213,"journal":{"name":"Expert Review of Anti-infective Therapy","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}