Gut Microbiome Diversity and Antimicrobial Resistance After a Single Dose of Oral Azithromycin in Children: A Randomized Placebo-Controlled Trial

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.

Antibiotic-associated neutropenia is marked by depletion of intestinalLachnospiraceaein pediatric patients

“…However, given the complexities of study enrollment and sample collection for pediatric patients, timeframes of up to +/- 1 week were established for said sample collections. Alteration of the intestinal microbiome occurs rapidly after antibiotic administration, even after a single dose; and recovery of the microbiome after antibiotic completion can take up to several months 21,22 . In our cohort, there was a wide variation of number of days between first dose of antibiotics and baseline stool sample collection with a median of 4.5 days (range 1-10 days) for the neutropenic group and a median of 3 days (range 1-10 day) for the control group; however, no statistically significant difference was found between groups for this variable (data not shown).…”

“…In particular, we wonder whether osteomyelitis' impact on bone marrow physiology, when combined with microbiota-mediated effects, may increase cytopenia risks. Even though some studies suggest that PO antibiotics impact the gut microbiome in a direct or local manner, and that IV antibiotics have an impact only through biliary excretion 35 ; recent studies typically link both IV and PO antibiotics with intestinal microbiota changes, including the well-studied influence of intrapartum IV antibiotic prophylaxis in neonatal microbiota composition 21,22,36,37 . Our detailed review did not reveal ICU-specific events that could further disrupt the intestinal microbiota and explain the correlation noted in our cohort.…”