Cesarean Section Optimal Antibiotic Prophylaxis (C/SOAP) Trial

描述（由研究者提供）：剖腹产最佳抗生素预防（C/SOAP）研究是一项大型实用多中心随机临床试验，旨在评价在手术切口前预防剖宫产术后感染时，基于阿奇霉素的广谱抗生素预防（阿奇霉素+标准窄谱头孢菌素）相对于标准单药头孢菌素的有效性和安全性。与头孢菌素相比，阿奇霉素对其他常见病原体有效，特别是支原体，当存在于绒毛膜羊膜中时，是剖宫产后子宫内膜炎的强危险因素，并且是伤口感染的最常见分离物。我们的初步研究表明，与单用标准头孢菌素相比，广谱预防可能有效降低剖宫产术后感染的风险。我们将招募那些尽管有标准预防措施但仍有剖宫产后感染高风险的妇女--那些在分娩过程中或在胎膜破裂后接受非选择性剖宫产的妇女。这些妇女面临着从下生殖道上行定植和感染脲原体的高可能性。在为期4年的项目期间，3个合作的围产期中心，国家承认他们的专业知识，在多中心临床试验的进行，将随机2000名妇女接受非选择性（计划外）剖宫产，术前开始静脉注射500 mg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啉预防（或克林霉素，如果对头孢菌素过敏）。根据CDC的建议，将对女性进行至少30天的随访，以确定手术部位感染。还将记录新生儿结局。具体目标1（有效性）：确定与单用标准头孢菌素相比，切口前广谱预防性治疗是否能降低计划外剖宫产女性的剖宫产后感染（尿道炎、伤口或其他感染）风险。{具体目标2（安全性）：评价基于阿奇霉素的切口前广谱预防治疗相对于标准头孢菌素预防治疗的安全性，包括不良复合和个体新生儿和母体结局的频率，包括疑似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和耐药微生物感染。} {具体目标3：采集和储存生物标本（脐带血和羊水）用于未来研究，主要是评估产前暴露于支原体与新生儿不良结局（全身炎症反应综合征、败血症、肺炎和支气管肺发育不良和死亡）之间的相关性，以及产前使用阿奇霉素预防这些结局的可能性。 公共卫生相关性：我们提出了一项大型多中心随机试验，以评估剖宫产时创新抗生素预防策略的益处和安全性，以减少感染的发生率，感染是美国妊娠相关死亡和疾病的5大原因之一。该方案在标准头孢菌素的基础上增加了第二种抗生素，以扩大对其他常见细菌的覆盖范围，特别是脲原体。来自一个中心的初步数据表明，这种广谱抗生素预防方案可能会显着减少剖宫产妇女的剖宫产后感染。本试验将在3个具有临床试验经验的妇产科进行：亚拉巴马大学伯明翰分校、北卡罗来纳州大学查佩尔山分校和德克萨斯大学医学分支（加尔维斯顿）。

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.