Effectiveness of antibiotic prophylaxis during surgical evacuation of the uterus for miscarriage management in low income countries. (AIMS Trial)

流产手术后感染——一个全球性问题：全球每年有2.1亿妇女怀孕，但其中3300万妇女以流产告终。大多数流产的妇女都会做手术。据报道，在低收入环境中，流产手术后的感染率高达30%。流产后感染可导致严重疾病和死亡，以及长期后果，包括宫外孕、不孕症和持续疼痛的发生率增加。预防性抗生素——一个潜在的解决方案：在手术前给予预防性抗生素，可能会改善预后。然而，对于流产手术，世卫组织现行指南、英国国家指南和低收入国家的国家指南不建议使用预防性抗生素。这是因为证据有限。我们建议，在手术时使用预防性抗生素，可能会提供一个解决方案，以减少流产后感染的严重问题。现有证据-需要试验：最近对所有证据的回顾得出结论，“没有足够的证据来评估对不完全流产妇女常规抗生素预防的政策”和“有一个真正的和迫切的需要找出抗生素是否应该在不完全流产的情况下常规使用。”这项研究产生的政策和成本影响将是巨大的，强烈建议进行随机临床试验，比较目前使用的抗生素和不使用抗生素。“拟议的AIMS试验：问题是：流产手术后盆腔感染能否通过在手术前给予妇女抗生素来减少？”研究地点：研究将在撒哈拉以南非洲的3个国家进行；坦桑尼亚，马拉维和乌干达。之所以选择这些国家，是因为低收入国家的妇女流产后感染问题最严重，因此这项研究可以在这些国家对改善健康产生最大影响。试验内容：接受流产手术的女性将被邀请参加，如果获得同意，她们将获得单剂量抗生素，在手术前两小时口服。我们计划在两年内共招募2400名女性。给予的治疗将是抗生素（400毫克强力霉素和400毫克甲硝唑）或假药丸（安慰剂）。妇女和临床医生将不知道药片是抗生素还是假药丸。通过比较两组患者术后头两周内的感染率和其他问题，如死亡或住院率，我们可以确定抗生素是否有效。任何发现感染的妇女都将得到适当的治疗和进一步的检查，以确定感染的原因。临床医生对试验的支持：该试验得到了国际专业组织的认可，对来自23个低收入国家的124名从业人员的调查绝大多数（87.5%）支持AIMS试验的必要性。用户支持和可接受性：对马拉维Blantyre和乌干达Mbale妇科住院患者进行的半结构化访谈表明，人们认识到流产后的潜在问题，并且拟议的方案是可以接受的。参与者表示他们愿意参与并返回进行后续评估。该试验也得到了流产患者协会的支持。该试验的潜在好处：流产手术很常见，感染并发症也很频繁和严重。预防性抗生素如果发现有效，可能是一种简单和负担得起的干预措施，可以迅速实施，以减轻低收入国家产妇死亡率和疾病的负担。这可以直接解决千年发展目标5（降低孕产妇死亡率）的问题，这方面的进展不平衡且缓慢。

Infection following miscarriage surgery - A GLOBAL PROBLEM:Globally, 210 million women become pregnant each year, but 33 million of these pregnancies end in a miscarriage. A majority of women with a miscarriage will have surgery. In low income settings, the infection rate after miscarriage surgery has been reported to be as high as 30%. Infection after miscarriage can result in serious illness and death, as well as long term consequences including increased rates of ectopic pregnancy, infertility and persistent pain.Prophylactic antibiotics - A POTENTIAL SOLUTION:Prophylactic antibiotics, given before surgery, may improve outcomes. However, for miscarriage surgery, current guidelines from the WHO, UK national guidelines, and national guidelines from low income countries do not recommend prophylactic antibiotics. This is because of limited evidence. We propose that prophylactic antibiotics, used at the time of surgery, may offer a solution to reducing the serious problem of infection following miscarriage.The existing evidence - A TRIAL IS NEEDED:A recent review of all the evidence concluded that "there is not enough evidence to evaluate a policy of routine antibiotic prophylaxis to women with incomplete miscarriage" and "There is a real and urgent need to find out whether antibiotics should be routinely used in cases of incomplete miscarriage. The policy and cost implications arising from this research will be tremendous, and randomised clinical trials comparing antibiotics currently in use with no antibiotics are strongly recommended."The proposed AIMS trial:The question: Can pelvic infection after miscarriage surgery be reduced by giving antibiotics to women just before surgery?Study sites: The study will be conducted in 3 countries in Sub-Saharan Africa; Tanzania, Malawi and Uganda. These countries have been chosen as women have the greatest problems with infection after miscarriage in low income countries and this is therefore the place where this research could have the greatest impact to improve health.What the trial involves: Women having surgery for miscarriage will be invited to participate, and if consent is given, women will be offered a single dose of antibiotics, to be taken by mouth two hours before the surgery. We plan to recruit 2400 women in total over 2 years.The treatment given will be either antibiotics (400mg doxycycline and 400mg metronidazole) or a dummy pill (placebo). The women and clinician will not know if the tablet is the antibiotic or the dummy pill. By comparing the rate of infection and other problems such as death or admission to hospital during the first 2 weeks after surgery between the groups we can determine if the antibiotics are having any effect. Any women in whom an infection is found will have appropriate treatment and also further tests to identify the cause of the infection.Clinician support for the trial:The trial is endorsed by international professional organisations and a survey of 124 practitioners from 23 low income countries overwhelmingly (87.5%) supported the need for the AIMS trial.User support and acceptability:Semi-structured interviews with gynaecology inpatients in Blantyre, Malawi and Mbale, Uganda showed there was recognition of the potential problems following miscarriage and that the proposed protocol was acceptable. Participants indicated they would be willing to participate and return for follow up assessments. The trial has also been endorsed by the patient group the Miscarriage Association.The potential benefits of the trial:Miscarriage surgery is common, and infective complications are frequent and serious. Prophylactic antibiotics, if found effective, may offer a simple and affordable intervention which could be rapidly implemented to reduce the burden of maternal mortality and disease in low income countries. This may directly address MDG5 (reducing maternal mortality), where progress has been uneven and slow.