Fecal Bacteriotherapy for Relapsing Clostridium difficile Infection

粪便细菌疗法治疗复发性艰难梭菌感染

• 批准号: 8383207
• 负责人: Colleen Renee Kelly
• 金额: $ 23.68万
• 依托单位: MIRIAM HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8383207
• 关键词: Adverse effects; Aftercare; Antibiotics; Bacteroides; Case Series; Case Study; Cessation of life; Clinical Trials; Clostridium difficile; Colectomy; Collaborations; Colon; Colonoscopy; Communities; Complex; Controlled Clinical Trials; Data; Diagnosis; Diarrhea; Disease; Donor Selection; Double-Blind Method; Drug resistance; Economic Burden; Epidemic; Face; Feces; Future; Gastrointestinal tract structure; Goals; Guidelines; Health; Hospitals; Immunologics; Incidence; Individual; Infection; Infectious Agent; Infusion procedures; Intestines; Literature; Maintenance; Metronidazole; North America; Oral; Patients; Pharmaceutical Preparations; Physiological; Placebos; Play; Population; Population Heterogeneity; Prevention; Publishing; Randomized; Randomized Controlled Clinical Trials; Recurrence; Recurrent disease; Refractory; Relapse; Reporting; Research; Research Personnel; Risk; Safety; Sampling; Screening procedure; Severities; Specimen; Toxin; Transplantation; Treatment Protocols; Vancomycin; alternative treatment; antimicrobial; antimicrobial drug; clinical care; cost; effective therapy; efficacy testing; experience; microbial; microbiome; novel; pathogen; patient safety; prevent; prospective; standard care; transmission process; treatment strategy

DESCRIPTION (provided by applicant): Clostridium difficile is a common nosocomial pathogen. By far the most common cause of infectious diarrhea in hospitalized patients in North America, there has been an alarming rise in incidence of C. difficile infection (CDI) since 2000. This rise has been accompanied by increasing rates of severe disease resulting in colectomy and/or death. Equally as concerning has been the increased incidence of community-associated CDI which has been reported in populations previously believed to be low risk. A common management problem in CDI is relapse, which occurs in up to 20% of patients after treatment of the initial infection. Patients who experience 1 recurrence have a 40% risk of further relapse and those with 2 or more episodes face a 60% risk. While the first relapse is generally treated with a second course of metronidazole or vancomycin, current guidelines recommend a tapering course of oral vancomycin, which is typically given over 4-8 weeks at a cost of $3500, after a second recurrence. Unfortunately, treatment options are limited for those patients who develop further recurrences. A number of patients become "vancomycin dependent," developing CDI relapse whenever this antibiotic is stopped. Antimicrobial agents are thought to alter the normal bacterial flora of the gastrointestinal tract so as to permit colonization and/or proliferation and toxin elaboration by C. difficile. The specific antimicrobials used to treat CDI also may predispose patients to further relapses through the maintenance of perturbed intestinal flora and may contribute to the emerging problems of drug resistance. Fecal microbiota transplantation (FMT) involves administration of feces from a healthy individual into a patient with relapsing CDI to promote recolonization with missing components of normal intestinal flora. The literature is limited to individual cases and case series, but these reported experiences with nearly 300 cases shows that FMT has cured relapsing CDI in a mean of 89% of patients treated. FMT appears to be safe, with no adverse effects or complications yet described, durable and inexpensive. To date there has not been a published prospective clinical trial of FMT for CDI. There is a need for research documenting efficacy as well as patient safety and tolerability. Standard treatment protocols also need to be developed. We propose to conduct a randomized, controlled clinical trial of FMT delivered at colonoscopy for treatment of relapsing CDI with the goal of establishing efficacy and safety data. This study includes collaboration with an investigator who will analyze the complex bacterial communities in stool collected from our subjects (before and after FMT) and their donors. Given the increasing incidence and severity of CDI, the problem of recurrent disease in a significant number of patients and the economic burden and drug-resistant infections associated with long- term use of oral vancomycin, it is important to determine whether FMT is effective for treatment of relapsing CDI. PUBLIC HEALTH RELEVANCE: There has been an alarming increase in the incidence and severity of Clostridium difficile infection (CDI) in North America over the past decade. Relapsing infection is a common problem in patients treated for CDI, often requiring prolonged and expensive courses of oral vancomycin with limited alternative treatment options. This study will determine if fecal microbiota transplantation, which involves administering fecal flora from a healthy stool donor to a patient with relapsing CDI, is an effective and safe treatment.

性状（由申请人提供）：艰难梭菌是一种常见的医院病原体。到目前为止，在北美住院患者中感染性腹泻的最常见原因是C。艰难梭菌感染（CDI）。这种上升伴随着导致结肠切除术和/或死亡的严重疾病的比率增加。同样令人担忧的是，社区相关CDI的发病率增加，这在以前被认为是低风险的人群中已有报道。CDI的一个常见管理问题是复发，在初始感染治疗后，高达20%的患者会复发。经历1次复发的患者有40%的进一步复发风险，而经历2次或2次以上复发的患者面临60%的风险。虽然第一次复发通常用甲硝唑或万古霉素的第二个疗程治疗，但目前的指南建议在第二次复发后口服万古霉素的逐渐减少的疗程，通常在4-8周内给予，费用为3500美元。不幸的是，对于那些进一步复发的患者，治疗选择有限。许多患者变得“万古霉素依赖”，每当停用这种抗生素时，就会发生CDI复发。抗微生物剂被认为改变胃肠道的正常细菌植物群，从而允许定植和/或增殖， 毒素加工C.很难用于治疗CDI的特定抗菌剂也可能通过维持受干扰的肠道植物群而使患者易于进一步复发，并可能导致新出现的耐药性问题。粪便微生物群移植（FMT）涉及将来自健康个体的粪便施用到患有复发性CDI的患者中，以促进正常肠道植物群的缺失组分的再生。文献仅限于个别病例和病例系列，但这些报道的近300例病例的经验表明，FMT治愈了平均89%接受治疗的患者的复发性CDI。FMT似乎是安全的，没有不良反应或并发症尚未描述，持久和廉价。迄今为止，尚未发表FMT治疗CDI的前瞻性临床试验。有必要进行研究，记录疗效以及患者的安全性和耐受性。还需要制定标准的治疗方案。我们建议进行一项在结肠镜检查时给予FMT治疗复发性CDI的随机对照临床试验，目的是建立疗效和安全性数据。本研究包括与一名研究者的合作，该研究者将分析从我们的受试者（FMT之前和之后）及其供体收集的粪便中的复杂细菌群落。鉴于CDI的发病率和严重程度不断增加，大量患者的疾病复发问题以及与长期口服万古霉素相关的经济负担和耐药性感染，确定FMT是否有效治疗复发性CDI非常重要。 公共卫生关系：在过去的十年中，北美艰难梭菌感染（CDI）的发病率和严重程度呈惊人的增长。复发性感染是接受CDI治疗的患者的常见问题，通常需要长期和昂贵的口服万古霉素疗程，替代治疗选择有限。这项研究将确定粪便微生物群移植是否是一种有效和安全的治疗方法，该移植涉及将来自健康粪便供体的粪便植物群给予复发性CDI患者。