Reduction of bloodstream infections from oral organisms in pediatric stem cell transplant: a randomized, multicenter, double-blind, placebo-controlled study evaluating twice daily oral xylitol

减少儿科干细胞移植中口腔生物体的血流感染：一项随机、多中心、双盲、安慰剂对照研究，评估每日两次口服木糖醇

• 批准号: 10176918
• 负责人: Christopher Eugene Dandoy
• 金额: $ 49.02万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-06 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10176918
• 关键词: Adherence; Admission activity; Adopted; Bacteremia; Bacteria; Bacterial Translocation; Blood Circulation; Bone Marrow Transplantation; Childhood; Clinical; Clinical Trials; Communicable Diseases; Data; Dental; Dental Plaque; Dentists; Diagnosis; Double-Blind Method; Fiber; Funding Opportunities; Gingiva; Gingivitis; Goals; Healthcare; Immune System Diseases; Incidence; Infection; Inflammation; Injury; Intensive Care Units; Intervention; Morbidity - disease rate; Mucositis; Mucous Membrane; Multi-Institutional Clinical Trial; National Institute of Dental and Craniofacial Research; Oral; Oral Ulcer; Oral cavity; Oral mucous membrane structure; Organism; Pathogenicity; Patients; Physicians; Population; Positioning Attribute; Prevention; Prevention strategy; Randomized; Research; Route; Saliva; Secondary to; Sepsis; Septic Shock; Specialist; Stem cell transplant; Streptococcus mitis; Sugar Alcohols; Testing; Time; Transplant Recipients; U-Series Cooperative Agreements; United States; Work; Xylitol; arm; base; clinically relevant; control trial; cost estimate; effectiveness evaluation; expectation; fruits and vegetables; graft vs host disease; improved outcome; injured; innovation; microbial; microbiome analysis; mortality; oral bacteria; oral care; oral infection; oral microbiome; oral plaque; placebo controlled study; preservation; prevent; response; standard of care

Abstract Bloodstream infections (BSI) caused by bacteria translocating across injured mucosa are a significant cause of morbidity and mortality in the 25,000 patients undergoing stem cell transplantation (SCT) in the United States each year. BSI secondary to translocation of oral organisms through damaged oral mucosaoccurs in nearly 16% of SCT recipients in the first three weeks after SCT despite current routine oral care. There are currently no known strategies to prevent post-SCT BSI from the translocation of bacteria through an injured mucosa. There is a critical need to identify preventive strategies to reduce BSI, and the oral mucosa as a specific route of entry has not been evaluated. In the absence of such information, SCT patients will continue to develop BSI from translocation of bacteria from mucosal barrier injury. Our long-term goal is to develop and disseminate clinically relevant and easily adoptable strategies to prevent BSI and improve outcomes after SCT. The overall objective of this proposal is to identify a clinically effective strategy to prevent or reduce BSI secondary to bacterial translocation through injured mucosa in the mouth. The rationale for the study is based on our baseline and pilot intervention data. The central hypothesis is that dental xylitol use, in addition to current oral care practice, are effective at reducing BSI from oral organisms, and decreasing the incidence of gingivitis, oral plaque, and oral ulcerations after SCT. Apart from our preliminary data, we are well-positioned to carry out the proposed work as we have a multicenter collaborative team consisting of pediatric bone marrow transplant physicians, dentists, and infectious disease specialists with focus and expertise in microbiome analyses. The following specific aims are proposed: AIM 1: Determine the effectiveness of twice-daily xylitol-wipe application on reducing BSI from oral organisms through a randomized, multicenter, double-blind, placebo-controlled study in pediatric SCT recipients. AIM 2: Determine the effectiveness of twice-daily xylitol-wipe application in reducing dental plaque, mucositis, oral GVHD, and gingival inflammation. AIM 3: Evaluate the influence of twice-daily xylitol-wipe application on oral microbiome diversity and saliva levels of pathogenic microbial species. The innovation of this proposal lies in the simplicity and affordability of the intervention. Xylitol is commercially available, inexpensive ($0.15 per application), non-toxic, and can be rapidly adopted into practice. If our hypotheses are proven, xylitol application could reduce the morbidity and mortality associated with BSI and decrease healthcare-associated costs of an estimated $40,000 per infection. At the successful completion of the proposed research, our expectation is to have demonstrated a significant reduction of bacteremia from oral organisms (Aim 1); decreased oral dental plaque, gingivitis, and oral ulceration (Aim 2); and preserved oral microbiome diversity and reduction of pathogenic microbial species in the oral cavity in those receiving daily dental xylitol wipe application (Aim 3) leading to substantial changes to the prevention of BSI in this population.

摘要 由细菌移位穿过受损粘膜引起的血流感染（BSI）是导致感染的重要原因。 在美国接受干细胞移植（SCT）的25，000例患者的发病率和死亡率 每年.继发于口腔微生物通过受损口腔粘膜移位的BSI发生在近16% 尽管目前进行常规口腔护理，但SCT后前三周内SCT接受者的数量仍然增加。目前没有 防止SCT后BSI细菌移位通过受损粘膜的已知策略。那里 迫切需要确定预防策略来减少BSI，并将口腔粘膜作为特定的进入途径 尚未进行评估。在缺乏此类信息的情况下，SCT患者将继续从 粘膜屏障损伤导致细菌移位。我们的长期目标是在临床上开发和传播 相关且易于采用的策略，以预防BSI并改善SCT后的结局。总体目标 该建议的目的是确定一种临床有效的策略，以预防或减少继发于细菌性BSI 通过口腔中受损的粘膜移位。这项研究的基本原理是基于我们的基线和试点 干预数据。中心假设是，牙科木糖醇的使用，除了目前的口腔护理实践， 有效减少口腔微生物的BSI，并降低牙龈炎、口腔菌斑和口腔溃疡的发生率。 SCT后溃疡。除了我们的初步数据外，我们已准备就绪，可以进行建议的工作 因为我们有一个多中心协作团队，由儿科骨髓移植医生，牙医， 和传染病专家，专注于微生物组分析。以下具体目标 目的1：确定每天两次木糖醇擦拭应用对减少BSI的有效性， 通过一项在儿科SCT中进行的随机、多中心、双盲、安慰剂对照研究 受惠人士目的2：确定每天两次木糖醇擦拭应用在减少牙菌斑方面的有效性， 粘膜炎、口腔GVHD和牙龈炎症。目的3：评价每天两次木糖醇擦拭的影响 应用于口腔微生物组多样性和病原微生物物种的唾液水平。的创新之处 建议的关键在于干预的简单性和可负担性。木糖醇是市售的，价格便宜 （每次0.15美元），无毒，可迅速应用于实践。如果我们的假设被证实，木糖醇 应用可降低与BSI相关的发病率和死亡率， 估计每例感染的费用为40，000美元。在成功完成拟议的研究后，我们的 预期已证明口腔微生物引起的菌血症显著减少（目标1）; 减少口腔牙菌斑、牙龈炎和口腔溃疡（目标2）;保持口腔微生物组多样性 以及减少每日接受木糖醇牙科擦拭物的患者口腔中的致病微生物种类 应用（目标3）导致该人群中BSI预防的实质性变化。