Mass azithromycin distribution tied to antibiotic resistance among children: NEJM

In previous studies, mass distributions of oral azithromycin twice a year to children 1 to 59 months of age reduced childhood mortality by 18% over 2 years in Niger, which suggested that this simple intervention could be a promising strategy for combating childhood mortality. The emergence of antibiotic resistance observed after 2 years of treatment calls into question the long-term effectiveness of such an intervention to reduce childhood mortality and arouses concern about the potential contribution of the intervention to the growing global burden of antibiotic resistance

To seek a greater understanding on this enigma,researchers investigated the gut resistancee of children after they received twice-yearly distributions of azithromycin for 4 years.

The team initiated an ancillary cluster-randomized trial in the Niger site of the MORDOR (Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance) trial in December 2014, concurrent with the main MORDOR trial. For the study sample,in the Niger site of the MORDOR trial, the research team enrolled 30 villages in a concurrent trial in which they were randomly assigned to receive mass distribution of either azithromycin or placebo, offered to all children 1 to 59 months of age every 6 months for 4 years.

Rectal swabs were collected at baseline, 36 months, and 48 months for analysis of the participants' gut resistome. The primary outcome was the ratio of macrolide-resistance determinants in the azithromycin group to those in the placebo group at 48 months.

On data analysis, the following facts emerged.

• Over the entire 48-month period, the mean (±SD) coverage was 86.6±12% in the villages that received placebo and 83.2±16.4% in the villages that received azithromycin.
• A total of 3232 samples were collected during the entire trial period; of the samples obtained at the 48-month monitoring visit, 546 samples from 15 villages that received placebo and 504 from 14 villages that received azithromycin were analyzed.
• Determinants of macrolide resistance were higher in the azithromycin group than in the placebo group: 7.4 times as high (95% confidence interval [CI], 4.0 to 16.7) at 36 months and 7.5 times as high (95% CI, 3.8 to 23.1) at 48 months.
• Continued mass azithromycin distributions also selected for determinants of nonmacrolide resistance, including resistance to beta-lactam antibiotics, an antibiotic class prescribed frequently in this region of Africa.

"This placebo-controlled, community-randomized trial showed that mass azithromycin distributions twice yearly for 4 years were associated with an increase in both macrolide- and nonmacrolide-resistance genes. Resistance surveillance should be an intrinsic component of any mass drug distribution program, and it can be achieved with metagenomic approaches." concluded the team.

For the full article follow the link: 10.1056/NEJMoa2002606

Primary source: New England Journal of Medicine