Research Project
10474098
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.
