Rapid Reduction of Campylobacter Species in the Gut Microbiome of Preschool Children after Oral Azithromycin: A Randomized Controlled Trial

Abstract

Campylobacter has emerged as a potential important cause of childhood morbidity in sub-Saharan Africa. Biannual mass azithromycin distribution has previously been shown to reduce all-cause child mortality in sub-Saharan Africa. We conducted a randomized controlled trial in Burkina Faso in which children were randomized in a 1:1 fashion to a 5-day course of azithromycin or placebo to investigate the effect of oral antibiotics on the gut microbiome. We evaluated the changes in the gut microbiome of preschool children treated with azithromycin using metagenomic DNA sequencing. We found that three Campylobacter species were reduced with azithromycin treatment compared with placebo. These results were consistent with other studies that have shown decreases in Campylobacter species after azithromycin treatment, generating the hypothesis that a decrease in Campylobacter may contribute to observations of reduction in mortality following azithromycin distribution.

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

“…In a smaller study where children in two rural communities of the Nouna District in Burkina Faso were individually randomized to receive a single course of three commonly prescribed antibiotics in the region, those receiving azithromycin showed a significant decrease in gut microbiome diversity and a relative reduction for Campylobacter species compared with children in the placebo arm. 11 Here, 157 species were differentially altered between treatment arms, including several Campylobacter and Clostridium species. Although these organisms are associated with disease, in the appropriate physiological context, even commensal organisms can be pathogenic.…”

Impact of antibiotics on gut microbiome composition and resistome in the first years of life in low- to middle-income countries: A systematic review

“… D’Souza (2020) [ 15 ], Doan (2017) [ 43 ], Doan (2018) [ 44 ], Doan (2019) [ 45 ], Doan (2020) [ 46 ], Hinterwirth (2020) [ 47 ], Oldenburg (2018) [ 48 ], Pickering (2022) [ 49 ], Oldenburg (2020) [ 50 ]. CTX, cotrimoxazole, AZI, azithromycin, AMX, amoxicillin.…”

The impact of mass drug administration of antibiotics on the gut microbiota of target populations

“…during the 2 week study period was reduced, and clearance of baseline infections with these enteric pathogens was increased among azithromycin-treated infants, as confirmed by polymerase chain reaction (PCR). [ 60 ] Two RCTs of single dose azithromycin (Niger [ 62 ] and Burkina Faso [ 63 ]) conducted in a comparable age group, also found a 27%–31% reduction in α-diversity [ 62 ], or a decrease in C. jejuni , C. ureolyticus , and C. hominis with azithromycin treatment [ 63 ]. However, α-diversity in children treated with amoxicillin or cotrimoxazole was not significantly altered [ 61 ].…”

“…Two cross-sectional studies and one prospective cohort study conducted in three high-income countries reported the association between IAP and gut microbiota composition during the neonatal period (Table 3 ). Microbiota α-diversity at 6–7 days of age was reduced in infants born to IAP-treated mothers [ 63 ]. Exposure to IAP was also associated with greater similarity in microbiota composition (i.e.…”

“…The IAP group was also dominated by Enterobacteriaceae, and depleted in Bifidobacterium spp. [ 63 ]. Finally, a prospective cohort study found a significant reduction in the relative abundance of the Actinobacteria phylum at 10 days of age (which includes Bifidobacterium ) and a significant increase in the Firmicutes phylum (which includes some notable pathogenic groups, including Staphylococcus , Listeria and Streptococcus , as well as probiotic groups, including Lactobacillus ) [ 64 ].…”