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

全球妇女儿童健康研究网络A-PLUS的补充 耐药性研究 项目摘要 全球网络目前正在进行一项阿奇霉素试验，以降低败血症的风险， 新生儿（A-PLUS）。需要了解的一个重要问题是抗生素耐药性的流行 阿奇霉素暴露的女性中。因此，这笔补充资金将用于支持正在进行的 从母亲和婴儿中连续收集临床标本，并检测这些标本的 培养至3个月的所有二分体的阿奇霉素耐药菌（不考虑6周时的耐药性） 并在产后6至12个月之间采集最终样本，用于母亲和婴儿的培养 样本（鼻咽[NP]和直肠）也通过培养检测阿奇霉素耐药菌。 所有时间点的样本将用于评估母体和婴儿微生物组，并评估 阿奇霉素预防性单次给药对耐药基因组的影响 任何潜在的生态失调的持续时间和微生物群落中抗性基因的存在。 具体而言，数据协调中心的补充资金将支持以下子研究的活动： * 促进样本采集，随后进行为期3个月的抗微生物耐药性检测 通过在产后6个月和12个月的母-婴配对子集中的最终样本采集 * 采购NP拭子和直肠拭子并将其运送至8个全球网络研究中心。 * 提供标签、跟踪和分析入组子研究的受试者。 * 管理从8个研究中心到UAB进行分析的样品运输，包括： o将NP拭子和直肠拭子样本置于干冰上的稳定缓冲液中， 位于伯明翰的亚拉巴马大学的全球网络站点。 o将常规临床培养物中的细菌分离株置于干冰上从8个全球 位于伯明翰的亚拉巴马大学的网络站点。 * 与微生物组和耐药组结局相关的统计数据分析 分析。 * 维护数据库与参与者的特点和成果，并使这些 数据可供公众使用，如所示。 总之，拟议的工作将解决全球关注的使用阿奇霉素在劳动 综合评价女性阿奇霉素耐药的危险性及变化 随着时间的推移，在参加研究的不同人群中， 全球网络审判如果没有补充资金和上述新的研究，我们将无法 能够最佳地确定这种情况下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， 有益于预防感染/死亡，并且还对儿童具有神经保护作用。此外，委员会认为， 否则，我们将无法完成对储存标本的任何微生物组研究， 不能进行耐药基因组研究，这将提供AMR模式的分子见解， 从而更全面地了解我们有希望的干预措施对AMR的影响， 微生物组由于样本量大，多个国家的网站，和高质量的细节，这 该提案有一个独特的机会，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.