Optimizing duration of antibiotics after valve surgery for infective endocarditis

描述(由申请人提供)：IE是一种潜在的致命感染，需要长时间的抗生素治疗。目前，对于接受外科瓣膜置换术治疗IE的患者术后抗生素的使用时间尚无共识。尽管美国心脏协会(AHA)的指南建议手术后最多使用6周的非肠道抗生素，但这一建议是基于判断而不是公布的证据。相比之下，在这些指导方针之后发表的大量证据现在表明，瓣膜手术后2周的抗生素治疗与较长疗程的治疗一样有效，特别是当手术时从瓣膜提取的组织培养显示致病病原体没有生长时。减少抗生素的使用为个体患者提供了几个潜在的好处，包括减少血管内导管和抗生素相关的并发症，选择耐药细菌分离株，以及成本。 与延长的非肠道抗生素治疗疗程有关。在目前的方案中，我们将设计一项多中心、随机的临床试验，对象是接受手术治疗的IE患者，他们将随机接受常规治疗，包括6周的抗生素治疗和缩短的2周抗生素治疗。主要结果将是12个月后治愈(无死亡或IE复发)；次要结果将是与抗生素使用和血管内导管使用有关的不良事件。目前提案的具体目标是(1)制定临床试验的方案和实施工具，以及(2)招募SIE参与临床试验。我们将通过利用世界上最大的学术临床研究组织杜克临床研究所(DCRI)和心内膜炎国际协作(ICE)的独特资源来实现这些目标，ICE是一个专注于IE研究的跨国研究网络。拟议的临床试验的总体目标 是为了证明抗生素治疗的持续时间可以缩短，同时保持对IE的有效治疗。这项临床试验的结果将允许临床医生对抗生素治疗的持续时间做出基于证据的决定，并可能减少不必要的抗生素使用。 公共卫生相关性：这项研究的总体目标是减少抗生素的使用，同时保持治疗IE的有效性。IE的抗生素治疗持续时间较短，可能会减少与抗生素相关的不良事件，并减少与用于输送非肠道抗生素的血管内导管有关的并发症，从而在个人层面上影响患者。从社会的角度来看，减少抗生素的使用有可能减少耐药菌株的选择，并降低与长期静脉注射抗生素治疗相关的成本。

DESCRIPTION (provided by applicant): IE is a potentially lethal infection requiring prolonged courses of antibiotic therapy. Currently, no consensus exists regarding duration of post-surgical antibiotics among patients undergoing surgical valve replacement for IE treatment. Although the American Heart Association (AHA) guidelines suggest up to 6 weeks of parenteral antibiotics following surgery, this recommendation is based on judgment rather than published evidence. By contrast, considerable evidence published subsequent to those guidelines now exists to suggest that 2 weeks of antibiotic therapy following valve surgery is as effective as longer courses of therapy, particularly when the tissue cultures taken from the valve at the time of surgery show no growth of the causative pathogen. A reduction in antibiotic use provides several potential advantages to the individual patient, including reductions in intravascular catheter and antibiotic-related complications, selection of resistant bacterial isolates, and costs related to extended courses of parenteral antibiotic therapy. In the current proposal we will design a multi- center, randomized clinical trial of patients who have undergone surgery for IE who will be randomized to usual treatment consisting of 6 weeks of antibiotic therapy versus a shortened 2 week course of antibiotic therapy. The primary outcome will be cure (absence of death or IE relapse) at 12 months; the secondary outcome will be adverse events related to antibiotic use and the use of intravascular catheters. The Specific Aims of the current proposal are to (1) develop the protocol and implementation tools for the clinical trial, and (2) recruit sies for participation in the clinical trial. We will accomplish these aims by leveraging the unique resources of the Duke Clinical Research Institute (DCRI), the world's largest academic clinical research organization and the International Collaboration on Endocarditis (ICE), a multinational network of investigators focused on research in IE. The overall goal of the proposed clinical trial is to demonstrate that the duration of antibiotic therapy can be reduced while maintaining effective treatment of IE. The results of this clinical trial will allow clinicians to make evidenc-based decisions regarding the duration of antibiotic therapy and will potentially reduce unnecessary antibiotic usage. PUBLIC HEALTH RELEVANCE: The overall goal of this study is to reduce antibiotic usage while maintaining effectiveness in treating IE. A shorter duration of antibiotic therapy for IE would impact patients on an individual level by potentially reducing antibiotic-related adverse events and reducing complications related to the intravascular catheters that are used to deliver parenteral antibiotics. From a societal perspective, a reduction in antibiotic usage has the potential to decrease selection of resistant bacterial isolates and to reduce costs related to prolonged intravenous antibiotic therapy.