Cesarean Section Optimal Antibiotic Prophylaxis (C/SOAP) Trial

描述(由研究人员提供)：剖宫产最佳抗生素预防(C/SOAP)研究是一项大型、务实的多中心随机临床试验，旨在评估基于阿奇霉素的广谱抗生素预防(阿奇霉素加标准窄谱头孢菌素)在手术切开前与标准单药头孢菌素预防剖宫产术后感染的比较有效性和安全性。与头孢菌素相比，阿奇霉素对其他常见病原体有效，特别是解脲支原体，当存在于绒毛膜时，解脲支原体是剖宫产后子宫内膜炎的强烈危险因素，也是最常见的伤口感染分离物。我们的初步研究表明，与标准头孢菌素相比，广谱预防可能有效地降低剖宫产后感染的风险。我们将招募剖宫产后感染的高危女性，尽管有标准的预防措施-那些在分娩期间或胎膜破裂后进行非选择性剖宫产的女性。这些妇女面临上升的定居和感染下生殖道的解脲支原体的可能性。在为期4年的项目期间，3个在进行多中心临床试验方面全国公认的合作围产期中心将随机选择2000名接受非选择性(非计划)剖宫产的妇女，接受手术前开始的500 mg静脉注射阿奇霉素或相同的安慰剂；同时，两组还将接受标准的单剂量头孢唑林预防(如果对头孢菌素过敏，则接受克林霉素)。根据疾控中心关于确定手术部位感染的建议，女性将接受至少30天的跟踪调查。新生儿的结局也将被记录下来。将讨论以下具体目标：具体目标1(有效性)：确定在接受非计划剖宫产的妇女中，与标准头孢菌素相比，切开前广谱预防是否可以降低剖宫产后感染(子宫内膜炎、伤口或其他感染)的风险。{具体目标2(安全性)：评估基于阿奇霉素的切开前广谱预防相对于标准头孢菌素预防的安全性，从不良综合和个别新生儿和母亲结局的频率方面，包括可疑或确诊的新生儿感染、药物反应或副作用，包括新生儿幽门狭窄，以及耐药生物感染。}{具体目标3：收集和储存生物标本(脐带血和羊水)以供未来研究，主要评估产前暴露于尿素血浆和不良新生儿结局(全身炎症反应综合征、败血症、肺炎、支气管肺发育不良和死亡)和产前使用阿奇霉素预防这些结局的可能性之间的关系。 公共卫生相关性：我们提出了一项大型多中心随机试验，以评估一种创新的抗生素预防策略在剖宫产中的益处和安全性，以降低感染的发生率，感染是美国与妊娠相关的死亡和疾病的前五大原因之一。该方案在标准头孢菌素中添加了第二种抗生素，以扩大对其他常见细菌的覆盖范围，特别是解脲支原体。来自单一中心的初步数据表明，这种广谱抗生素预防方案可能显著减少剖宫产产妇的剖宫产后感染。这项试验将在3个在进行临床试验方面经验丰富的妇产科部门进行：阿拉巴马大学伯明翰分校、北卡罗来纳大学、教堂山分校和加尔维斯顿的德克萨斯大学医学部。

DESCRIPTION (provided by investigator): The Cesarean Section Optimal Antibiotic Prophylaxis (C/SOAP) study is a large pragmatic multi-center randomized clinical trial designed to evaluate the comparative effectiveness and safety of azithromycin-based extended-spectrum antibiotic prophylaxis (azithromycin plus standard narrow-spectrum cephalosporin) relative to standard single-agent cephalosporin prior to surgical incision to prevent post-cesarean infection. In contrast to cephalosporin, azithromycin is effective against other common pathogens, especially ureaplasma, a strong risk factor for post-cesarean endometritis when present in the chorioamnion, and the most common isolate from wound infections. Our preliminary studies suggest that extended-spectrum prophylaxis may effectively lower the risk of post-cesarean infection compared to standard cephalosporin alone. We will enroll women at high risk for post-cesarean infection despite standard prophylaxis - those undergoing a non-elective cesarean during labor or after membrane rupture. These women face a high likelihood of ascending colonization and infection with ureaplasmas from the lower genital tract. During the 4-year project period, 3 collaborating perinatal centers, recognized nationally for their expertise in the conduct of multi-center clinical trials, will randomize 2000 women undergoing non-elective (unscheduled) cesarean to either 500mg of intravenous azithromycin or identical placebo initiated prior to surgery; concurrently, both groups will also receive standard single-dose cefazolin prophylaxis (or clindamycin if allergic to cephalosporin). Women will be followed for at least 30 days according to CDC recommendations for ascertaining surgical site infections. Neonatal outcomes will also be recorded. The following specific aims will be addressed: Specific aim 1 (Effectiveness): To determine if pre-incision extended-spectrum prophylaxis reduces the risk of post-cesarean infection (endometritis, wound or other infections) compared to standard cephalosporin alone among women undergoing unscheduled cesarean delivery. {Specific aim 2 (Safety): To evaluate the safety of azithromycin-based pre-incision extended spectrum prophylaxis relative to standard cephalosporin prophylaxis in terms of the frequency of adverse composite and individual neonatal and maternal outcomes including suspected or proven neonatal infection, drug reactions or side effects including neonatal pyloric stenosis, and infection with resistant organisms.} {Specific aim 3: To collect and store biological specimens (umbilical cord blood and amniotic fluid) for future studies, primarily to assess the association between prenatal exposure to ureaplasmas and adverse neonatal outcomes (systemic inflammatory response syndrome, sepsis, pneumonia and bronchopulmonary dysplasia and death) and the potential for prenatal azithromycin use to prevent these outcomes.} PUBLIC HEALTH RELEVANCE: We propose a large multi-center randomized trial to evaluate the benefits and safety of an innovative antibiotic prophylaxis strategy at cesarean delivery to reduce the incidence of infection, one of the top 5 causes of pregnancy-related death and illness in the US. The regimen adds a second antibiotic to the standard cephalosporin to extend the spectrum of coverage to other common bacteria especially ureaplasmas. Preliminary data from a single center suggest that this extended-spectrum antibiotic prophylaxis regimen may significantly reduce post-cesarean infections among women undergoing cesarean delivery. The trial will be conducted at 3 Ob/Gyn departments experienced in the conduct of clinical trials: University of Alabama at Birmingham, University of North Carolina, Chapel Hill and University of Texas Medical Branch in Galveston.