Mass distribution of azithromycin shown to increase antibiotic resistance

1. Children in African villages that received scheduled azithromycin displayed increased antibiotic resistance compared to ones that received a placebo.

2. An increase in nonmacrolide resistance genes was also observed.

Evidence Rating Level: 1 (Excellent)

Study Rundown: In order to combat childhood mortality in sub-Saharan Africa, oral azithromycin has been administered to children less than 59 months of age biyearly. However, an increase in the prevalence of antibiotic resistance has been seen. This study examined the relationship between gut resistome and azithromycin administration administered biyearly, over a course of four years in children living in Africa. Rectal swabs were examined at different points throughout the study to determine antibiotic resistance in two study groups. At 48 months, the results revealed increased macrolide-resistance in the azithromycin group when compared to the placebo group. The study successfully displayed that mass distribution of antibiotics may lead to broad antibiotic resistance by randomizing participants across the continent and comparing to a control group. However, the study was limited by absence of phenotypic assessment of the rectal sample and a lack of clinical history (no symptoms were collected when sample was obtained).

Click to read the study in NEJM

Relevant Reading: Longer-term assessment of azithromycin for reducing childhood mortality in Africa

In-Depth [randomized controlled trial]: This study was conducted in nonurban communities of Niger between December 2014 and June 2019. Children below 59 months of age were enrolled and randomized into the study if they had a body weight of 3800g or greater using R software. An oral azithromycin suspension or placebo suspension was administered to the study participants at 0, 6, 12, 18, 24, 30, 36 and 42 months of age. If macrolide allergy was present, then the participant was excluded from the study. A rectal sample was collected at baseline, and then at 36 and 48 months. A total of 3232 samples was collected over the course of the study. The mean age of the Placebo group was 31, 30, and 32 months at the baseline, 36 month and the 48 month visit respectively. The mean age of the azithromycin group was 31 months at the baseline. At 36 months, the results showed 7.4 times increased in macrolide resistance within the azithromycin group when compared to the placebo group. Whereas, at 48 months, the results displayed an increase of 7.5 times increased macrolide resistance when compared to the placebo. An increase in nonmacrolide resistance genes was also seen with this study.

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