Efficacy of oral vancomycin prophylaxis for prevention of recurrent C. difficile infection

艰难梭菌(简称艰难梭菌)是一种对公共卫生具有重大意义的病原体，也是目前世界上最大的 与医疗保健相关的腹泻的常见原因，复发率高， 尤其是在那些再次接受抗菌治疗的患者中。美国疾病控制与预防中心的数据 据控制和预防中心估计，2011年发生了453,000起艰难梭菌事件 感染(CDI)导致29,300人死亡。在美国，CDI每年的成本估计为 6亿美元。不幸的是，近三分之一首次感染的患者将 发生复发，随后复发的风险随着每一次发作而增加。抗生素 在最初的CDI消退后，针对其他感染性疾病给予的治疗可能会引发CDI复发 这一集。预防CDI复发对于减少无数的身体、社会和 伴随着反复发作的心理后果。万古霉素预防用药 可能会降低复发的风险，但尚未得到很好的研究。我们建议使用多中心安慰剂- 150例随机双盲对照试验的疗效评价 每日口服125 mg万古霉素与安慰剂预防CDI复发的比较 在过去90天内至少经历过一次CDI发作并正在接受 抗生素用于非CDI疾病。此外，我们将评估这种治疗对 肠道微生物区系组成、功能与万古霉素耐药肠道定植 肠球菌(VRE)。受试者在完成万古霉素或其他药物治疗后将接受为期8周的追踪。 安慰剂治疗。主要结果将是反复发生的CDI。程序将包括 收集至少3份粪便样本，并在整个研究过程中完成3份粪便日记 研究访问(基线，口服万古霉素完成，并在治疗结束后8周 治疗)。研究结果不仅将决定口服万古霉素预防的疗效，而且 此外，还深入了解口服万古霉素对粪便微生物区系和VRE的影响 殖民主义。鉴于抗生素管理的关键重要性，重要的是检查 在潜在的好处和可能的不利影响之间进行权衡，例如肠道生物失调。如果是口头的 万古霉素预防被发现是有效的，它将改变目前在 预防CDI复发的途径。

Clostridium difficile (C. difficile) is a pathogen of major public health importance and the most common cause of healthcare-associated diarrhea, with high rates of recurrent disease, especially in those re-exposed to antimicrobial therapy. Data from the Centers for Disease Control and Prevention estimate that in 2011 there were 453,000 incident episodes of C. difficile infections (CDI) resulting in 29,300 deaths. The annual cost from CDI in the US is estimated at 1.3 billion dollars. Unfortunately, nearly one third of patients who develop initial infection will develop recurrence, and risk of subsequent recurrence increases with each episode. Antibiotics given for other infectious conditions may trigger CDI recurrence after resolution of initial CDI episode. Preventing CDI recurrence is essential to reduce the myriad physical, social, and psychological consequences that accompany recurrent episodes. Prophylaxis with vancomycin may reduce risk of recurrence but has not been well studied. We propose a multicenter placebo- controlled double blind randomized controlled trial (RCT) in 150 subjects to evaluate the efficacy of prophylaxis with 125 mg daily oral vancomycin versus placebo for preventing recurrent CDI in patients who have experienced at least one CDI episode in the last 90 days and are receiving antibiotics for a non CDI condition. In addition, we will evaluate the impact of this treatment on the gut microbiota composition and function and gut colonization by vancomycin-resistant enterococcus (VRE). Subjects will be followed for 8 weeks after completing vancomycin or placebo treatment. The primary outcome will be recurrent CDI. Procedures will include collection of at least 3 stool samples, and completion of stool diaries throughout the study with 3 study visits (baseline, completion of oral vancomycin and at 8 weeks following the end of therapy). Study findings will not only determine the efficacy of oral vancomycin prophylaxis, but also provide insight into the effect of oral vancomycin on the fecal microbiota and VRE colonization. With the critical importance of antibiotic stewardship, it is important to examine the trade-off between a potential benefit and possible adverse effects such as gut dysbiosis. If oral vancomycin prophylaxis is found to be efficacious it will shift the current paradigm in the approach to prevention of recurrent CDI.