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: 9272833
• 负责人: WILLIAM J STEINBACH
• 金额: $ 54.25万
• 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 2019-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9272833
• 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 Trials Data Monitoring Committees; Cohort Studies; Collection; Communicable Diseases; Consensus; Data; Diagnosis; Disease; Drug Kinetics; Enrollment; Epidemiology; Evidence based treatment; Expert Opinion; Formulation; Foundations; Frequencies; Goals; Guidelines; Hematology; Hematopoietic Stem Cell Transplantation; Hospitalized Child; Ii-Key; Immune; Incidence; Infection; Inferior; Intensive Care Units; International; Knowledge; Level of Evidence; Mission; Modeling; Morbidity - disease rate; Multicenter Studies; Mycoses; Neonatal; 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; cohort; compare effectiveness; epidemiology study; evidence base; high risk; improved; improved outcome; mortality; novel; oncology; pediatric patients; 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）：侵袭性念珠菌病是高危住院儿童中常见且经常致命的感染。协调一致的努力已经改善了成人患者侵袭性念珠菌病的预防和治疗，但在改善儿童预后方面所做的工作却很少。因此，针对侵袭性念珠菌病治疗的实践指南包含的儿童数据有限且未经充分验证。这种缺乏儿科特异性的 由于两个人群之间存在重大差异，因此信息令人担忧。我们的首要目标是为儿童侵袭性念珠菌病制定新的循证治疗指南。我们将前瞻性地招募 600 名儿童参加一项跨国队列研究 儿科侵袭性念珠菌病的研究，以比较当前儿科抗真菌治疗（两性霉素 B、三唑和棘白菌素）的有效性。我们还将验证我们之前得出的针对在儿科重症监护病房发生念珠菌血症的患者的临床预测模型。这一验证将使我们能够定义经验性抗真菌治疗的最佳临床方案。该提案将重点关注两个具体目标：1) 比较棘白菌素与两性霉素 B 或三唑抗真菌疗法治疗儿童侵袭性念珠菌病的有效性。目前尚不清楚儿童的最佳抗真菌治疗。我们假设，与接受两性霉素 B 或三唑类抗真菌药物治疗的儿童相比，接受棘白菌素治疗的侵袭性念珠菌病儿童的总体反应会高出 10%。 2) 验证儿科重症监护中念珠菌血症的临床预测模型 单元。我们小组之前的工作已经从单个中心推导出了一个预测模型，我们的目标是验证该模型并评估其在多个中心的普遍性。我们假设临床预测模型将准确地对风险最高的儿童进行分类，识别出念珠菌血症风险 > 10% 的患者，从而为适当且有针对性的预防或经验性治疗策略提供信息。我们的研究团队为开展这项研究做好了独特的准备。十多年来，研究人员在众多项目中共同合作。该研究团队将利用我们组建的独特的多中心联盟，即国际儿科真菌网络 (PFN)。 PFN 由全球 32 个站点组成，由传染病、血液学/肿瘤学和造血干细胞移植领域的儿科专家领导。这项研究的影响将是确定治疗儿童侵袭性念珠菌病最有效的抗真菌疗法，并验证一个模型，以准确识别重症监护病房中患念珠菌血症风险最高的儿童。完成后，我们将获得新的数据来推进美国传染病学会念珠菌病治疗指南的推荐强度从 C 级到 B 级，以及儿童侵袭性念珠菌病治疗关键组成部分的证据质量从 III 级到 II 级。这将改善儿童的预后。

项目成果

Failure to Validate a Multivariable Clinical Prediction Model to Identify Pediatric Intensive Care Unit Patients at High Risk for Candidemia.

未能验证多变量临床预测模型来识别念珠菌血症高风险的儿科重症监护病房患者。

• 发表时间: 2016-12
• 影响因子: 3.2
• 作者: Fisher, Brian T;Ross, Rachael K;Roilides, Emmanuel;Palazzi, Debra L;Abzug, Mark J;Hoffman, Jill A;Berman, David M;Prasad, Priya A;Localio, A Russell;Steinbach, William J;Vogiatzi, Lambrini;Dutta, Ankhi;Zaoutis, Theoklis E
• 通讯作者: Zaoutis, Theoklis E

Comparative Effectiveness of Echinocandins vs Triazoles or Amphotericin B Formulations as Initial Directed Therapy for Invasive Candidiasis in Children and Adolescents.

棘白菌素与三唑或两性霉素 B 制剂作为儿童和青少年侵袭性念珠菌病初始定向治疗的有效性比较。

• 发表时间: 2021-08-10
• 影响因子: 3.2
• 作者: Fisher, Brian T;Zaoutis, Theoklis E;Xiao, Rui;Wattier, Rachel L;Castagnola, Elio;Pana, Zoi Dorothea;Fullenkamp, Allison;Boge, Craig L K;Ross, Rachael K;Yildirim, Inci;Palazzi, Debra L;Danziger;Vora, Surabhi B;Arrieta, Antonio;Yi
• 通讯作者: Yi