Probiotics to Improve Outcomes of Clostridium difficile

益生菌可改善艰难梭菌的治疗结果

基本信息

批准号：
8516939
负责人：
NASIA SAFDAR
金额：
$ 7.11万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8516939
关键词：
Activities of Daily Living Address Adherence Adult Adverse effects Age-Years Americas Antibiotic Resistance Antibiotic Therapy Antibiotics Antibody Formation Area Bacteria Biological Products Caring Centers for Disease Control and Prevention (U.S.)Clinical Trials Clinics and Hospitals Clostridium Clostridium difficile Communicable Diseases Control Groups Controlled Clinical Trials Data Data Collection Diarrhea Double-Blind Method Elderly Electronics Epidemiology Feces Food Goals Guidelines Healthcare Hospitalization Immunity Incidence Infection Infection prevention Injectable Intervention Lactobacillus casei rhamnosus Lactoferrin Legal patent Life Methods Microbiology Monoclonal Antibodies National Hospital Discharge Survey Nutritional Oral Outcome Patients Placebo Control Placebos Population Population Study Predisposing Factor Prevalence Probiotics Production Public Health Quality of life Randomized Recommendation Recovery Recurrence Research Risk Societies Specimen Symptoms Telephone Testing Therapeutic Toxin Universities Vulnerable Populations Wisconsin Work abstracting adverse outcome age group age related aged antimicrobial bacterial resistance base cost cytokine density diaries dietary supplements disorder prevention experience functional status gastrointestinal high risk immune function improved indexing meetings methicillin resistant Staphylococcus aureus microorganism mortality novel older patient pathogen pathogenic bacteria portability primary outcome sample collection standard care standard of care systematic review tool young adult

项目摘要

DESCRIPTION (provided by applicant): Clostridium difficile is a major pathogen causing serious healthcare-associated infection. Compared with younger adults, adults 60 years of age and older have an increased incidence of Clostridium difficile infection (CDI) and are far more likely to suffer adverse consequences of CDI such as prolonged diarrhea symptoms, reduced functional ability, recurrence, mortality and prolonged hospitalization. Thus, our proposed area of study, CDI is directly relevant to the healthcare needs and quality of life of older adults. However, therapeutic options for CDI are limited. We propose a pilot feasibility clinical trial in subjects receiving care at the University of Wisconsin Hospital and Clinics Madison, WI to evaluate the use of a biotherapeutic agent, Lactobacillus rhamnosus HN001, as an adjunct to antibiotic treatment to reduce the duration of diarrhea in hospitalized patients with a first episoe of CDI. We have two hypotheses: (1) The probiotic L. rhamnosus HN001, when compared with placebo, will reduce the duration of diarrhea in patients with CDI (2) The probiotic L. rhamnosus HN001, when compared with placebo, will reduce CDI recurrence, fecal lactoferrin levels, and quantity of C. difficile toxin while improving functional status. To investigate these hypotheses, we are proposing the following specific aims: SPECIFIC AIM 1: To determine the efficacy of adjunctive probiotic use during a first episode of CDI to reduce the duration of diarrhea in patients with CDI compared to standard of care and placebo SPECIFIC AIM 2: To determine the efficacy of adjunctive probiotic use during a first episode of CDI to reduce CDI recurrence compared to standard of care and placebo SPECIFIC AIM 3 (Exploratory): To determine the effect of adjunctive probiotic use during a first episode of CDI on density of C. difficile toxin i stool, stool cytokines, fecal lactoferrin and functional status. Our study population includes hospitalized patients at the University of Wisconsin Hospital and Clinics who have a first episode of CDI. Potential subjects will be identified by reviewing microbiology lists of patients with CDI. Subjects with CDI will be randomized to probiotic or placebo for 4 weeks in addition to usual antibiotic treatment of CDI according to standard of care. Duration of followup is 8 weeks. Stool specimens will be collected at baseline, 4 weeks and 8 weeks. The primary outcome is duration of diarrhea. Data collection will occur by use of stool diaries, stool sample collection and electronic chart review. Adherence will be encouraged by weekly phone calls. The study will provide important preliminary pilot data for a subsequent larger study to examine the efficacy of probiotics for CDI. If found to be efficacious and feasible in the older adult population, probiotis represent an easily implementable, safe, and well-tolerated intervention that may prove a useful adjunctive treatment for CDI.

描述（由申请人提供）：艰难梭菌是导致严重医疗保健相关感染的主要病原体。与年轻人相比，60岁及以上的成年人艰难梭菌感染（CDI）的发病率更高，并且更有可能遭受CDI的不良后果，例如长期腹泻症状、功能能力下降、复发、死亡和住院时间延长。因此，我们提出的研究领域 CDI 与老年人的医疗保健需求和生活质量直接相关。然而，CDI 的治疗选择有限。我们提议在威斯康星州麦迪逊市威斯康星大学医院和诊所接受护理的受试者中进行一项试点可行性临床试验，以评估生物治疗剂鼠李糖乳杆菌 HN001 作为抗生素治疗的辅助药物的使用，以减少住院患者腹泻的持续时间与 CDI 的第一集。我们有两个假设：(1) 与安慰剂相比，益生菌鼠李糖乳杆菌 HN001 将减少 CDI 患者的腹泻持续时间 (2) 与安慰剂相比，益生菌鼠李糖乳杆菌 HN001 将减少 CDI 复发，粪便乳铁蛋白水平和艰难梭菌毒素数量，同时改善功能状态。为了研究这些假设，我们提出以下具体目标：具体目标 1：确定与标准护理和安慰剂相比，在 CDI 首次发作期间辅助使用益生菌以缩短 CDI 患者腹泻持续时间的功效具体目标2：确定与标准护理和安慰剂相比，在 CDI 首次发作期间辅助使用益生菌减少 CDI 复发的功效具体目标 3 （探索性）：确定首次 CDI 期间辅助使用益生菌对粪便中艰难梭菌毒素密度、粪便细胞因子、粪便乳铁蛋白和功能状态的影响。我们的研究人群包括威斯康星大学医院和诊所首次发生 CDI 的住院患者。将通过审查 CDI 患者的微生物学名单来确定潜在受试者。患有 CDI 的受试者除了根据护理标准接受 CDI 的常规抗生素治疗外，还将随机接受益生菌或安慰剂治疗 4 周。随访时间为 8 周。将在基线、第 4 周和第 8 周收集粪便样本。主要结局是腹泻持续时间。数据收集将通过粪便日记、粪便样本收集和电子图表审查来进行。每周都会通过电话鼓励大家遵守规定。该研究将为后续更大规模的研究提供重要的初步试点数据，以检验益生菌对 CDI 的功效。如果发现益生菌在老年人群中有效且可行，那么益生菌代表了一种易于实施、安全且耐受性良好的干预措施，可能被证明是 CDI 的有用辅助治疗。