Cesarean Section Optimal Antibiotic Prophylaxis (C/SOAP) Trial

剖宫产最佳抗生素预防（C/SOAP）研究是一项大型实用多中心随机临床试验，旨在评估手术切口前以阿奇霉素为基础的广谱抗生素预防（阿奇霉素加标准窄谱头孢菌素）相对于标准单药头孢菌素预防剖宫产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，尤其是脲原体，当存在于绒毛膜时，脲原体是剖宫产后子宫内膜炎的一个强危险因素，也是伤口感染中最常见的分离物。我们的初步研究表明，与单独使用标准头孢菌素相比，广谱预防可有效降低剖宫产后感染的风险。我们将招募有标准预防措施的高危剖宫产后感染的妇女-那些在分娩期间或膜破裂后进行非选择性剖宫产的妇女。这些妇女极有可能上升定植和感染来自下生殖道的脲原体。在为期4年的项目期间，在开展多中心临床试验方面获得全国认可的3家合作围产期中心将随机分配2000名接受非选择性（计划外）剖宫产的妇女，在术前开始静脉注射500毫克阿奇霉素或相同的安慰剂；同时，两组患者也将接受标准单剂量头孢唑林预防治疗（如果对头孢菌素过敏，可使用克林霉素）。根据疾病预防控制中心确定手术部位感染的建议，将对妇女进行至少30天的随访。新生儿结局也将被记录。具体目的1（有效性）：确定在计划外剖宫产妇女中，与单独使用标准头孢菌素相比，切口前广谱预防是否能降低剖宫产后感染（子宫内膜炎、伤口或其他感染）的风险。{具体目标2（安全性）：评估阿奇霉素为基础的切口前扩展谱预防相对于标准头孢菌素预防的安全性，在新生儿和产妇的不良综合和个体结局的频率方面，包括疑似或已证实的新生儿感染、药物反应或副作用，包括新生儿幽门狭窄，以及耐药菌感染。{具体目的3：收集和储存生物标本（脐带血和羊水）用于未来的研究，主要是评估产前暴露于脲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）之间的关系，以及产前使用阿奇霉素预防这些结局的可能性。}

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.