Multi-center studies to improve diagnosis and treatment of pediatric candidiasis

改善儿童念珠菌病诊断和治疗的多中心研究

• 批准号: 8668897
• 负责人: WILLIAM J STEINBACH
• 金额: $ 59.73万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8668897
• 关键词: Address; Adult; Advisory Committees; Americas; Amphotericin B; Antifungal Agents; Antifungal Therapy; Area; Aspergillosis; Biological Markers; Candidiasis; Characteristics; Child; Child Care; Childhood; Clinical; Clinical Treatment; Clinical Trials Data Monitoring Committees; Cohort Studies; Collection; Communicable Diseases; Consensus; Data; Diagnosis; Disease; Drug Formulations; Drug Kinetics; Enrollment; Epidemiologic Studies; Epidemiology; Evidence based treatment; Expert Opinion; Foundations; Frequencies; Goals; Guidelines; Hematology; Hematopoietic Stem Cell Transplantation; Hospitalized Child; Immune; Incidence; Infection; Inferior; Intensive Care Units; International; Knowledge; Lead; Level of Evidence; Mission; Modeling; Morbidity - disease rate; Mycoses; Neonatal; Outcome; Patients; Pediatric Intensive Care Units; Pediatrics; Population; Practice Guidelines; Prevention; Publications; Recommendation; Regimen; Research; Research Personnel; Review Committee; Risk; Risk Factors; Seminal; Site; Societies; Therapeutic; Therapeutic Intervention; Triazoles; Validation; Work; authority; candidemia; clinical epidemiology; cohort; compare effectiveness; evidence base; high risk; improved; mortality; novel; oncology; prospective; public health relevance; response; treatment strategy

DESCRIPTION (provided by applicant): Invasive candidiasis is a common and frequently fatal infection in high-risk hospitalized children. Coordinated efforts have improved the prevention and treatment of invasive candidiasis in adult patients, but little work has been done to improve outcomes in children. As a result, practice guidelines addressing the treatment for invasive candidiasis contain limited and poorly validated data for children. This lack of pediatric-specific information is concerning as major differences exist between the two populations. Our overarching objective is to develop new evidence-based treatment guidelines for invasive candidiasis in children. We will prospectively enroll 600 children in a multi-national cohort study of pediatric invasive candidiasis to compare the effectiveness of current pediatric antifungal treatments (amphotericin B, triazoles, and echinocandins). We will also validate our previously derived clinical prediction model for patients developing candidemia while in the pediatric intensive care unit. This validation will allow us to define the optimal clinical scenario for empirical antifungal therapy. This proposal will focus on two specific aims: 1) Compare the effectiveness of echinocandin versus amphotericin B or triazole antifungal therapy for pediatric invasive candidiasis. Optimal antifungal therapy for children is currently unknown. We hypothesize that children with invasive candidiasis treated an echinocandin will have a 10% greater global response compared to children treated with either amphotericin B or triazole antifungals. 2) Validate a clinical prediction model for candidemia in the pediatric intensive care unit. Previous work by our group has derived a prediction model from a single center and we aim to validate the model and assess its generalizability in multiple centers. We hypothesize that the clinical prediction model will accurately classify children at highest risk, identifying patients with a > 10% risk of developing candidemia, and therefore inform appropriate and targeted preventative or empirical treatment strategies. Our study team is uniquely poised to conduct this research. The investigators have functioned together as collaborators on numerous projects for over a decade. This research team will leverage the unique multi- center consortium we have assembled known as the International Pediatric Fungal Network (PFN). The PFN is composed of 32 worldwide sites led by pediatric subspecialists in infectious diseases, hematology/oncology, and hematopoietic stem cell transplantation. The impact of this research will be to define the most effective antifungal therapy for pediatric invasive candidiasis and validate a model to accurately identify those children in the intensive care unit at highest risk fr developing candidemia. Upon completion, we will have new data to advance the Infectious Diseases Society of America treatment guidelines for candidiasis strength of recommendation from C to B and the quality of evidence from level III to II for the key components of management of invasive candidiasis in children. This will lead to improved outcomes in children.

描述（由申请人提供）：侵入性念珠菌病是高危住院儿童的常见且经常致命的感染。协调的努力改善了成年患者的侵入性念珠菌病的预防和治疗，但几乎没有为改善儿童预后所做的工作。结果，解决侵入性念珠菌病治疗的实践指南包含有限且经过验证的儿童数据。缺乏小儿特异性 信息是关于两个人群之间存在的主要差异。我们的总体目标是制定针对儿童入侵性念珠菌病的新的基于证据的治疗指南。我们将前瞻性地招募600名儿童参加跨国队列研究 小儿浸润性念珠菌病以比较当前的小儿抗真菌治疗（两性霉素B，三唑和echinocandins）的有效性。我们还将验证我们在小儿重症监护病房期间在患有候选血症的患者中验证我们先前衍生的临床预测模型。这种验证将使我们能够定义经验抗真菌治疗的最佳临床情况。该提案将重点放在两个具体目标上：1）比较在儿科浸润性念珠菌症中，比较棘齿素与两性霉素B或三唑抗真菌疗法的有效性。目前尚不清楚儿童的最佳抗真菌治疗。我们假设患有侵入性念珠菌病治疗的儿童与用两性霉素B或三唑抗真菌抗体治疗的儿童相比，全球反应的全球反应要高10％。 2）验证小儿重症监护术中候选血症的临床预测模型 单元。我们小组的先前工作从一个中心得出了一个预测模型，我们旨在验证该模型并评估其在多个中心的概括性。我们假设临床预测模型将准确地对处于最高风险的儿童进行分类，从而确定患有候选血症的风险> 10％的患者，因此为适当且有针对性的预防或经验治疗策略提供了信息。我们的学习团队独特地准备进行这项研究。十多年来，调查人员一直在众多项目中担任合作者。该研究团队将利用我们组装的独特多个中心财团，称为国际儿科真菌网络（PFN）。 PFN由32个全球部位组成，由传染病，血液学/肿瘤学和造血干细胞移植中的儿科专科医生领导。这项研究的影响是定义针对小儿浸润性念珠菌病的最有效的抗真菌疗法，并验证模型，以准确地确定重症监护病房中的那些儿童，处于最高风险的FR FR发展念珠菌。完成后，我们将拥有新的数据，以推动美国念珠菌病至B的推荐强度的美国传染病协会治疗指南，以及从III级到II的证据质量，用于儿童入侵性念珠菌病的关键组成部分。这将导致儿童的结果改善。