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

摘要 由细菌跨损伤粘膜转移引起的血流感染(BSI)是导致 美国2.5万例干细胞移植(SCT)患者的发病率和死亡率 每年。近16%的口腔生物通过受损的口腔粘膜移位继发BSI 尽管目前常规的口腔护理，但接受SCT的患者在SCT后的前三周内。目前没有 已知的预防SCT后BSI细菌通过受损粘膜移位的策略。那里 迫切需要确定预防策略，以减少BSI，并将口腔粘膜作为一种特定的进入途径 还没有经过评估。在缺乏这些信息的情况下，SCT患者将继续从 粘膜屏障损伤引起的细菌移位。我们的长期目标是开发和传播临床应用 相关和易于采用的策略，以预防BSI和改善SCT后的结果。总体目标 这项建议的目的是确定一种临床上有效的策略来预防或减少继发于细菌的BSI 通过口腔中受损的粘膜进行移位。这项研究的理论基础是基于我们的基准和试点 干预数据。中心假设是，除了目前的口腔护理实践外，牙科木糖醇的使用还 有效减少口腔微生物的细菌感染，降低牙周炎、牙菌斑和口腔疾病的发生率。 SCT后的溃疡。除了我们的初步数据外，我们有能力进行拟议的工作 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、 以及在微生物组分析方面具有重点和专业知识的传染病专家。以下是具体目标 建议：目标1：确定每天两次使用木糖醇擦拭对减少 儿童SCT中口腔微生物的随机、多中心、双盲、安慰剂对照研究 收件人。目的2：确定每天两次使用木糖醇擦拭减少牙菌斑的效果。 粘膜炎、口腔移植物抗宿主病和牙周炎。目的3：评价每天两次木糖醇擦拭的效果。 口腔微生物群落多样性和唾液病原微生物种类水平的应用。它的创新之处在于 建议在于干预的简单性和可负担性。木糖醇可以在市场上买到，价格低廉 (每个应用0.15美元)，无毒，并可迅速应用于实践。如果我们的假设得到证实，木糖醇 应用程序可以降低与BSI相关的发病率和死亡率，并减少与医疗保健相关的 估计每次感染的成本为40,000美元。在成功完成拟议的研究后，我们的 预期已显示口腔微生物的菌血症显著减少(目标1)； 减少口腔菌斑、牙周炎和口腔溃疡(目标2)；并保存口腔微生物多样性 每天接受牙科木糖醇擦拭的患者口腔中致病微生物种类的减少 应用(目标3)导致在这一人群中预防血吸虫病的实质性变化。

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.