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

描述（由申请人提供）：侵袭性念珠菌病是一种常见的和经常致命的感染高风险住院儿童。协调一致的努力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做得很少。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缺乏有效性。这种缺乏儿科特异性的 这一信息令人担忧，因为两个群体之间存在重大差异。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。我们将在一项多国队列研究中前瞻性招募600名儿童 儿童侵袭性念珠菌病的研究，以比较目前儿童抗真菌治疗（阿替霉素B、三唑和棘白菌素）的有效性。我们还将验证我们先前推导的儿科重症监护病房患者发生念珠菌血症的临床预测模型。这一验证将使我们能够确定经验性抗真菌治疗的最佳临床方案。该建议将集中于两个具体目标：1）比较棘白菌素与阿替霉素B或三唑抗真菌治疗儿童侵袭性念珠菌病的有效性。儿童的最佳抗真菌治疗目前尚不清楚。我们假设，侵袭性念珠菌病患儿用棘白菌素治疗的总体反应比用阿替霉素B或三唑类抗真菌药治疗的患儿高10%。2)儿科重症监护中念珠菌血症的临床预测模型 单位我们小组以前的工作已经从一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适性。我们假设临床预测模型将准确地将儿童分类为最高风险，识别出发生念珠菌血症风险> 10%的患者，从而为适当的和有针对性的预防或经验性治疗策略提供信息。我们的研究团队是唯一准备进行这项研究。十多年来，这些研究人员在许多项目中共同合作。这个研究小组将利用我们所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个研究中心组成，由感染性疾病、血液学/肿瘤学和造血干细胞移植领域的儿科亚专家领导。这项研究的影响将是确定最有效的抗真菌治疗儿科侵袭性念珠菌病，并验证一个模型，以准确地确定那些在重症监护病房的儿童在发展念珠菌血症的最高风险。完成后，我们将有新的数据，以推进美国传染病学会念珠菌病治疗指南的建议强度从C到B和证据质量从III级到II级的关键组成部分的管理侵袭性念珠菌病的儿童。这将改善儿童的结果。

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.