@article {1031, title = {Gut Resistome after Antibiotics among Children with Uncomplicated Severe Acute Malnutrition: A Randomized Controlled Trial.}, journal = {Am J Trop Med Hyg}, volume = {107}, year = {2022}, month = {2022 Jul 13}, pages = {59-64}, abstract = {

A broad-spectrum antibiotic, typically amoxicillin, is included in many country guidelines as part of the management of uncomplicated severe acute malnutrition (SAM) in children without overt clinical symptoms of infection. Alternative antibiotics may be beneficial for children with SAM without increasing selection for beta-lactam resistance. We conducted a 1:1 randomized controlled trial of single dose azithromycin versus a 7-day course of amoxicillin for SAM. Children 6-59 months of age with uncomplicated SAM (mid-upper arm circumference \< 11.5 cm and/or weight-for-height Z-score \< -3) were enrolled in Boromo District, Burkina Faso, from June through October 2020. Rectal swabs were collected at baseline and 8 weeks after treatment and processed using DNA-Seq. We compared the resistome at the class level in children randomized to azithromycin compared with amoxicillin. We found no evidence of a difference in the distribution of genetic antibiotic resistance determinants to any antibiotic class 8 weeks after treatment. There was no difference in genetic macrolide resistance determinants (65\% azithromycin, 65\% placebo, odds ratio, OR, 1.00, 95\% confidence interval, CI, 0.43-2.34) or beta-lactam resistance determinants (82\% azithromycin, 83\% amoxicillin, OR 0.94, 95\% CI, 0.33-2.68) at 8 weeks. Although presence of genetic antibiotic resistance determinants to macrolides and beta-lactams was common, we found no evidence of a difference in the gut resistome 8 weeks after treatment. If there are earlier effects of antibiotics on selection for genetic antibiotic resistance determinants, the resistome may normalize by 8 weeks.

}, keywords = {Amoxicillin, Anti-Bacterial Agents, Azithromycin, Child, Drug Resistance, Bacterial, Humans, Macrolides, Severe Acute Malnutrition}, issn = {1476-1645}, doi = {10.4269/ajtmh.22-0007}, author = {Oldenburg, Catherine E and Hinterwirth, Armin and Ourohir{\'e}, Millogo and Dah, Clarisse and Ou{\'e}draogo, Moussa and Sie, Ali and Boudo, Valentin and Chen, Cindi and Ruder, Kevin and Zhong, Lina and Lebas, Elodie and Nyatigo, Fanice and Arnold, Benjamin F and O{\textquoteright}Brien, Kieran S and Doan, Thuy} } @article {231, title = {A double-masked placebo-controlled trial of azithromycin to prevent child mortality in Burkina Faso, West Africa: Community Health with Azithromycin Trial (CHAT) study protocol.}, journal = {Trials}, volume = {20}, year = {2019}, month = {2019 Dec 04}, pages = {675}, abstract = {

BACKGROUND: Biannual, mass azithromycin distribution has previously been shown to reduce all-cause child mortality in sub-Saharan Africa. Subgroup analysis suggested that the strongest effects were in the youngest children, leading to the hypothesis that targeting younger age groups might be an effective strategy to prevent mortality. We present the methods of two randomized controlled trials designed to evaluate mass and targeted azithromycin distribution for the prevention of child mortality in Burkina Faso, West Africa.

METHODS/DESIGN: The Child Health with Azithromycin Treatment (CHAT) study consists of two nested, randomized controlled trials. In the first, communities are randomized in a 1:1 fashion to biannual, mass azithromycin distribution or placebo. The primary outcome is under-5 all-cause mortality measured at the community level. In the second, children attending primary healthcare facilities during the first 5-12 weeks of life for a healthy child visit (e.g., for vaccination) are randomized in a 1:1 fashion to a single orally administered dose of azithromycin or placebo. The primary outcome is all-cause mortality measured at 6 months of age. The trial commenced enrollment in August 2019.

DISCUSSION: This study is expected to provide evidence on two health systems delivery approaches (mass and targeted treatment) for azithromycin to prevent all-cause child mortality. The results will inform global and national policies related to azithromycin for the prevention of child mortality.

TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03676764. Registered on 19 September 2018; prospectively registered pre results.

}, keywords = {Anti-Bacterial Agents, Azithromycin, Child Mortality, Child, Preschool, Double-Blind Method, Humans, Infant, Outcome Assessment, Health Care, Randomized Controlled Trials as Topic, Sample Size}, issn = {1745-6215}, doi = {10.1186/s13063-019-3855-9}, author = {Sie, Ali and Ouattara, Mamadou and Bountogo, Mamadou and Bagagnan, Cheik and Coulibaly, Boubacar and Boudo, Valentin and Lebas, Elodie and Brogdon, Jessica M and Lin, Ying and B{\"a}rnighausen, Till and Porco, Travis C and Doan, Thuy and Lietman, Thomas M and Oldenburg, Catherine E} }