Catalytic, Regioselective C-H Activation/Oxidation of Substituted Arenes

描述(由申请人提供)：腹内感染的抗生素治疗的最佳持续时间尚不清楚，已被外科感染学会确定为临床研究的高度优先事项。我们研究的最终目标是优化(和减少)全世界腹内感染的抗生素治疗持续时间。要测试的假设是，与在适当的手术或经皮干预的情况下基于生理参数的解决方案相比，四天的腹内感染治疗将导致类似的结果和较短的治疗持续时间。这项建议是一项多中心、随机、双盲(直到治疗第四天)、非劣势的临床试验，将预先确定的四天抗生素治疗与在白细胞计数正常化(=11,000/ul)和系统温度正常化(&lt；38.0℃)一天后终止的抗生素治疗进行比较，整个历日(和最长10天的抗生素治疗)设置为复杂的腹部感染进行充分的源头控制。纳入标准包括年龄=16岁，是否有能力获得患者或代孕者的知情同意，是否存在需要住院的任何时间的腹内感染并通过开腹、腹腔镜或经皮介入治疗，以及当地调查员和首席调查员认为是否有足够的源头控制。将招募1120名患者，以确保有足够的权力评估两个手臂的等效性。主要终点将是根据分配的抗生素治疗持续时间(治疗意图分析)而定的失败率。失败将被定义为需要再次干预(手术或经皮)，手术部位感染，或在最初的腹部感染干预后30天内死亡。此外，还将评估多个次级终点，包括抗生素治疗的持续时间以及非腹部和非手术伤口部位的感染发生率，特别是具有抗生素耐药性的病原体。我们研究的最终目标是改变世界各地的做法，特别是通过缩短腹内感染的抗生素治疗时间，从而减少资源利用和减少对抗生素耐药病原体的选择。

DESCRIPTION (provided by applicant): The optimum duration of antibiotic therapy for intraabdominal infection remains unknown and has been identified by the Surgical Infection Society as a high priority for clinical research. The ultimate objective of our research is to optimize (and reduce) the duration of antibiotic therapy for intraabdominal infection throughout the world. The hypothesis to be tested is that four days of therapy for intraabdominal infection will lead to similar outcomes and a shorter duration of therapy when compared to a course based on the resolution of physiologic parameters in the setting of adequate operative or percutaneous intervention. This proposal is for a multicenter, randomized, double-blind (until the fourth day of therapy), non-inferiority clinical trial comparing a predetermined four days of antibiotic therapy to antibiotic therapy terminated one day after normalization of white blood cell count (= 11,000/ul) and normalization of systemic temperature (< 38.0¿ C) for one whole calendar day (and a maximum of 10 days of antibiotic therapy) in the setting of complicated intraabdominal infection treated with adequate source control. Inclusion criteria include age = 16 years, ability to obtain informed consent from the patient or surrogate, presence of an intraabdominal infection requiring any duration of hospitalization and managed with open, laparoscopic, or percutaneous intervention, and, adequate source control in the opinion of the local investigator and Principal Investigator. 1,120 patients will be enrolled to ensure adequate power to assess equivalence of the two arms. The primary endpoint will be percentage failure conditioned by assigned duration of antibiotic therapy (intent to treat analysis). Failure will be defined as need for reintervention (surgical or percutaneous), surgical site infection, or death within 30 days of the original intervention for intraabdominal infection. In addition, multiple secondary endpoints will be assessed, including duration of antibiotic therapy and the incidence of infection at non-abdominal and non-surgical wound sites, particularly with antibiotic-resistant pathogens. The ultimate objective of our research is to change practice throughout the world, specifically by shortening the duration of antibiotic therapy for intraabdominal infections and thus decreasing resource utilization and decreasing the selection of antibiotic-resistant pathogens.