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: 10688676
• 负责人: Christopher Eugene Dandoy
• 金额: $ 51.46万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10688676
• 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; Randomized Controlled Trials; 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; 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.

抽象的 由细菌跨过受损粘膜移位引起的血流感染 (BSI) 是导致 美国 25,000 名接受干细胞移植 (SCT) 的患者的发病率和死亡率 每年。近 16% 的人会因口腔微生物通过受损的口腔粘膜移位而继发 BSI 尽管目前有常规口腔护理，但 SCT 接受者在 SCT 后的前三周内仍然存在这种情况。目前没有 防止 SCT 后 BSI 细菌通过受损粘膜移位的已知策略。那里 迫切需要确定减少 BSI 的预防策略，并将口腔粘膜作为特定的进入途径 尚未评估。如果缺乏此类信息，SCT 患者将继续发展为 BSI 粘膜屏障损伤引起的细菌易位。我们的长期目标是在临床上开发和传播 预防 BSI 并改善 SCT 后结果的相关且易于采用的策略。总体目标 该提案的目的是确定一种临床有效的策略来预防或减少细菌继发的 BSI 通过口腔中受损的粘膜移位。该研究的基本原理基于我们的基线和试点 干预数据。中心假设是，除了当前的口腔护理实践之外，牙科木糖醇的使用也 有效减少口腔微生物引起的 BSI，并减少牙龈炎、口腔菌斑和口腔溃疡的发生率 SCT后出现溃疡。除了我们的初步数据外，我们还准备好开展拟议的工作 因为我们有一个由儿科骨髓移植医生、牙医组成的多中心协作团队， 以及专注于微生物组分析并具有专业知识的传染病专家。具体目标如下 建议： 目标 1：确定每日两次木糖醇擦拭应用对于减少 BSI 的有效性 通过儿科 SCT 的随机、多中心、双盲、安慰剂对照研究对口腔微生物进行研究 收件人。目标 2：确定每天两次木糖醇擦拭物在减少牙菌斑方面的有效性， 粘膜炎、口腔 GVHD 和牙龈炎症。目标 3：评估每日两次木糖醇擦拭的影响 口腔微生物组多样性和唾液病原微生物物种水平的应用。本次的创新 建议在于干预措施的简单性和可负担性。木糖醇是市售的，价格便宜 （每次应用 0.15 美元）、无毒，并且可以快速应用于实践。如果我们的假设得到证实，木糖醇 应用可以降低与 BSI 相关的发病率和死亡率，并减少与医疗保健相关的 每次感染的费用估计为 40,000 美元。在成功完成拟议的研究后，我们 期望能够显着减少口腔微生物引起的菌血症（目标 1）； 减少口腔牙菌斑、牙龈炎和口腔溃疡（目标 2）；并保留口腔微生物组的多样性 每天使用木糖醇擦牙巾的人口腔中致病微生物种类的减少 应用（目标 3）导致该人群 BSI 预防发生重大变化。