@article {1361, title = {Gut Microbiome Diversity and Antimicrobial Resistance After a Single Dose of Oral Azithromycin in Children: A Randomized Placebo-Controlled Trial.}, journal = {Am J Trop Med Hyg}, year = {2024}, month = {2024 Jan 16}, abstract = {

Mass antibiotic distribution to preschool children resulted in alterations of the gut microbiome months after distribution. This individually randomized, placebo-controlled trial evaluated changes in the gut microbiome and resistome in children aged 8 days to 59 months after one dose of oral azithromycin in Burkina Faso. A total of 450 children were randomized in a 1:1 ratio to either placebo or azithromycin. Rectal samples were collected at baseline, 2 weeks, and 6 months after randomization and subjected to DNA deep sequencing. Gut microbiome diversity and normalized antimicrobial resistance determinants for different antibiotic classes were evaluated. Azithromycin decreased gut bacterial diversity (Shannon P < 0.0001; inverse Simpson P < 0.001) 2 weeks after treatment relative to placebo. Concurrently, the normalized abundance of macrolide resistance genetic determinants was 243-fold higher (95\% CI: 76-fold to 776-fold, P < 0.0001). These alterations did not persist at 6 months, suggesting that disruptions were transient. Furthermore, we were unable to detect resistance changes in other antibiotic classes, indicating that co-resistance with a single course of azithromycin when treated at the individual level was unlikely.

}, issn = {1476-1645}, doi = {10.4269/ajtmh.23-0651}, author = {Doan, Thuy and Liu, Zijun and Sie, Ali and Dah, Clarisse and Bountogo, Mamadou and Ouattara, Mamadou and Coulibaly, Boubacar and Kiemde, Dramane and Zonou, Guillaume and Nebie, Eric and Brogdon, Jessica and Lebas, Elodie and Hinterwirth, Armin and Zhong, Lina and Chen, Cindi and Zhou, Zhaoxia and Porco, Travis and Arnold, Benjamin F and Oldenburg, Catherine E and Lietman, Thomas M} } @article {216, title = {Adverse Events and Clinic Visits following a Single Dose of Oral Azithromycin among Preschool Children: A Randomized Placebo-Controlled Trial.}, journal = {Am J Trop Med Hyg}, year = {2020}, month = {2020 Dec 21}, abstract = {

Biannual mass azithromycin distribution reduces all-cause child mortality in some settings in sub-Saharan Africa; however, adverse events and short-term infectious outcomes following treatment have not been well characterized. Children aged 0-59 months were recruited in Nouna Town, Burkina Faso, and randomized 1:1 to a single directly observed oral 20 mg/kg dose of azithromycin or placebo. At 14 days after treatment, caregivers were interviewed about adverse event symptoms their child experienced since treatment and if they had sought health care for their child. All children had tympanic temperature measured at the 14-day visit. We compared adverse events and clinic visits using logistic regression models between azithromycin- and placebo-controlled children. Of 450 children enrolled, 230 were randomized to azithromycin and 220 to placebo. On average, children were aged 28 months, and 50.9\% were female. Caregivers of 20\% of children reported that their child experienced at least one adverse event, with no significant difference between study arms (19.9\% azithromycin; 20.0\% placebo, logistic regression = 0.96). Vomiting was more often reported by caregivers of azithromycin-treated children than by those of placebo-treated children (7.2\% azithromycin, 1.9\% placebo, logistic regression = 0.01). There were no significant differences in other adverse events or clinic visits. Adverse events following a single oral dose of azithromycin in preschool children were rare and mild. Azithromycin administration appears safe in this population.

}, issn = {1476-1645}, doi = {10.4269/ajtmh.20-1002}, author = {Sie, Ali and Dah, Clarisse and Bountogo, Mamadou and Ouattara, Mamadou and Nebie, Eric and Coulibaly, Boubacar and Brogdon, Jessica M and Godwin, William W and Lebas, Elodie and Doan, Thuy and Arnold, Benjamin F and Porco, Travis C and Lietman, Thomas M and Oldenburg, Catherine E} } @article {131, title = {Neonatal azithromycin administration to prevent infant mortality: study protocol for a randomised controlled trial.}, journal = {BMJ Open}, volume = {9}, year = {2019}, month = {2019 09 04}, pages = {e031162}, abstract = {

INTRODUCTION: Biannual mass azithromycin distribution to children aged 1-59 months has been shown to reduce all-cause mortality. Children under 28 days of age were not treated in studies evaluating mass azithromycin distribution for child mortality due to concerns related to infantile hypertrophic pyloric stenosis (IHPS). Here, we report the design of a randomised controlled trial to evaluate the efficacy and safety of administration of a single dose of oral azithromycin during the neonatal period.

METHODS AND ANALYSIS: The (NAITRE) study is a double-masked randomised placebo-controlled trial designed to evaluate the efficacy of a single dose of azithromycin (20 mg/kg) for the prevention of child mortality. Newborns (n=21 712) aged 8-27 days weighing at least 2500 g are 1:1 randomised to a single, directly observed, oral dose of azithromycin or matching placebo. Participants are followed weekly for 3 weeks after treatment to screen for adverse events, including IHPS. The primary outcome is all-cause mortality at the 6-month study visit.

ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Boards at the University of California, San Francisco in San Francisco, USA (Protocol $\#$18-25027) and the Comit{\'e} National d{\textquoteright}Ethique pour la Recherche in Ouagadougou, Burkina Faso (Protocol $\#$2018-10-123). The findings of this trial will be presented at local, regional and international meetings and published in open access peer-reviewed journals.

TRIAL REGISTRATION NUMBER: NCT03682653; Pre-results.

}, keywords = {Anti-Bacterial Agents, Azithromycin, Body Size, Body Weight, Child Development, Double-Blind Method, Humans, Infant, Infant Mortality, Infant, Newborn, Randomized Controlled Trials as Topic}, issn = {2044-6055}, doi = {10.1136/bmjopen-2019-031162}, author = {Sie, Ali and Bountogo, Mamadou and Nebie, Eric and Ouattara, Mamadou and Coulibaly, Boubacar and Bagagnan, Cheik and Zabre, Pascal and Lebas, Elodie and Brogdon, Jessica and Godwin, William W and Lin, Ying and Porco, Travis and Doan, Thuy and Lietman, Thomas M and Oldenburg, Catherine E} }