Fecal Bacteriotherapy for Relapsing Clostridium difficile Infection

描述（申请人提供）：艰难梭菌是一种常见的医院病原体。艰难梭菌感染（CDI）是迄今为止北美住院患者感染性腹泻最常见的原因，自2000年以来，艰难梭菌感染（CDI）的发病率出现了惊人的上升。这一增长伴随着导致结肠切除术和/或死亡的严重疾病的增加。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有报道。CDI的一个常见管理问题是复发，高达20%的患者在初始感染治疗后复发。1次复发的患者有40%的复发风险，2次或以上复发的患者有60%的复发风险。虽然第一次复发通常用甲硝唑或万古霉素治疗第二个疗程，但目前的指南建议在第二次复发后，口服万古霉素的疗程逐渐减少，通常在4-8周内服用，费用为3500美元。不幸的是，对于那些进一步复发的患者，治疗选择是有限的。许多患者变得“依赖万古霉素”，一旦停止使用这种抗生素，CDI就会复发。抗菌剂被认为可以改变胃肠道的正常菌群，从而允许定植和/或增殖

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.