Global Network for Women's and Children's Health Research Data Coordinating Center

全球妇女和儿童健康研究网络A+增刊 细菌耐药性研究 项目摘要 全球网络目前正在进行阿奇霉素的试验，以降低脓毒症和 新生儿(A+)。一个需要理解的重要问题是抗菌素耐药性的流行 在接触阿奇霉素的女性中。因此，这一补充将用于支持正在进行的 从母亲和婴儿身上连续收集临床标本，并对这些标本进行检测 对阿奇霉素耐药细菌培养至3个月，用于所有二联体(无论在6周内耐药) 产后6至12个月的最终样本采集，用于母婴培养 样本(鼻咽[NP]和直肠)也要通过培养来检测阿奇霉素耐药性细菌。 所有时间点的样本都将被用来评估母婴微生物组，并评估 单剂预防性阿奇霉素对耐药性的鉴定和测定 微生物群落中任何潜在的生物失调和抗性基因存在的持续时间。 具体而言，数据协调中心的补充资金将支持下面概述的分组研究的活动： *促进样本收集，随后进行为期3个月的抗菌素耐药性测试 通过在产后6个月和12个月在母婴亚组中收集最终样本 *为8个全球网络站点采购和运送NP棉签和直肠棉签用品。 *提供参与分项研究的参与者的标签、跟踪和分析 *管理从8个地点运往联合检查所进行分析的样本，包括： O将NP拭子和直肠拭子样本放在干冰上的稳定缓冲液中从8 阿拉巴马大学伯明翰分校的全球网络站点。 O从全球8个国家的干冰上运送常规临床培养的细菌分离物 亚拉巴马大学伯明翰分校的网络站点。 *统计数据分析与微生物组和耐药组结果的关系 分析。 *维护具有参与者特征和结果的数据库，并使这些 可供公众使用的数据，如图所示。 总之，拟议的工作将解决全球对在分娩中使用阿奇霉素的担忧 对阿奇霉素耐药风险进行综合评估的妇女和 母婴微生物群和耐药菌群随时间的变化以及登记的不同人群 全球网络试验。如果没有补充资金和上述新研究，我们将不会 能够以最佳方式确定抗菌素耐药模式的风险程度和持续时间 对接触阿奇霉素的妇女和儿童进行的大型多国研究，这可能是 有益于预防感染/死亡，对儿童也有神经保护作用。此外， 否则，我们将无法完成对储存标本的任何微生物组研究，并将 不能进行抗药性研究，这些研究将提供对AMR模式和 从而更全面地了解我们有希望的干预措施对AMR和 微生物组。由于样本量大，多个国家/地区的站点，以及高质量的细节，这 提案有一个独特的机会来彻底回答这个简单、低成本的安全问题 干预。

Supplement for the Global Network for Women’s and Children’s Health Research’s A-PLUS Antimicrobial Resistance Study Project Summary The Global Network is currently undertaking a trial of azithromycin to reduce risk of sepsis and newborns (A-PLUS). An important question to understand is the prevalence of antimicrobial resistance among women exposed to azithromycin. Thus, this supplement will be used to support the ongoing serial collection of clinical specimens from mothers and infants, and testing of these specimens for Azithromycin-resistant bacteria by culture to 3 months for all dyads (regardless of resistance at 6 weeks) and a final sample collection between 6 and 12 months post-partum for culture of maternal and infant samples (Nasopharyngeal [NP]and rectal) to also test for Azithromycin-resistant bacteria by culture. Samples from all timepoints will be used to assess the maternal and infant microbiome and to assess the effects of the single dose of prophylactic azithromycin on the resistome by identifying and determining the duration of any potential dysbiosis and presence of resistance genes in the microbial communities. Specifically, supplemental funds to the data coordinating center will support the activities of the sub-study outlined below: * Facilitating sample collection, testing for anti-microbial resistance for 3 month duration followed by final sample collection at 6 and 12 months post-partum in sub-set of mother -infant dyads * Procuring and shipping supplies for NP swabs and rectal swabs to the 8 Global Network Sites. * Providing labels, tracking and analyses of participant’s enrolled in the sub-study. * Managing the shipments of samples from the 8 sites to UAB for analyses, including: o shipping NP swabs and rectal swab specimens in stabilizing buffer on dry ice from the 8 Global Network Sites to the University of Alabama at Birmingham. o shipping bacterial isolates from routine clinical cultures on dry ice from the 8 Global Network Sites to University of Alabama at Birmingham. * Statistical data analyses of the associations with outcomes to the microbiome and resistome analyses. * maintaining the database with the participant characteristics and outcomes and make these data available for public use, as indicated. In summary, the proposed work will address the global concerns about use of azithromycin in laboring women with a comprehensive evaluation of the risk of azithromycin resistance and the changes in maternal-neonatal microbiome and resistome over time and across the diverse populations enrolled in the Global Network Trial. Without the supplemental funds and the above new studies, we will not be able to optimally determine the extent and duration of risk of antimicrobial resistance patterns in this large multi-country study of women and children who were exposed to azithromycin which may be beneficial in preventing infection/mortality and also be neuroprotective for the children. Furthermore, we will otherwise not be able to complete any of the microbiome studies on stored specimens and will not be able to conduct resistome studies which will provide molecular insights into AMR patterns and thereby provide a more complete picture of the effects of our promising intervention on the AMR and microbiome. Because of the large sample size, multi-country sites, and high quality to detail, this proposal has a unique opportunity to thoroughly answer the question of safety in this simple, low-cost intervention.