DISCUSSION
CNS INFECTIONS
Phenotypic resistance prevalence values for macrolide and nonmacrolide antibiotics in Our results show some interesting consistencies and differences with resistance determinants from gut microbiota sampled from the same individuals at 36 months. Resistance determinants of macrolides and nonmacrolides in gut microbiota were significantly higher in the azithromycin treatment group than in the placebo group,It is not clear why resistance increased in the placebo villages. One possibility is that children gained exposure to resistant strains at schools where children from placebo and azithromycin treatment villages mix. Another possibility is that children in placebo villages experienced greater antibiotic exposure after the trial due to a general global trend of increased antibiotic use. In both explanations, social mixing among children in different intervention clusters would lead to greater exposure. A better understanding of the geographic proximities, seasonal mobility (e.g., school, work), and other measures of social connectivity among communities would help future efforts to predict resistance emergence and spread.A major limitation of our study, because this trial was randomized at the village level and children were selected at random each year to provide a nasopharyngeal swab, is that we can only make inferences about prevalence at the community level. Longitudinal studies on an individual level could yield additional information, such as how often individuals with resistant phenotypes revert to susceptible and the timescale of such transitions.This study provides perspective on the risk-benefit of MDA distribution programs. Although the study lacks the power to make definitive statistical statements regarding the relationship between MDA and antibiotic emergence, a few qualitative conclusions are supported. Namely, MDA does appear to promote antibiotic resistance, but the population-level impact appears to plateau. To concretely evaluate the short-term benefits of MDA programs versus the long-term risks of antibiotic resistance, more studies are needed to evaluate the clinical significance of increased community-level colonization with resistant organisms and to determine how long the increased prevalence of antibiotic resistance persists after MDA cessation. It is also important to further evaluate the extent to which MDA distribution in a particular community may impact the risk of antibiotic infections in neighboring communities. These types of studies will help clarify when MDA programs can be safely deployed to save lives and decrease morbidity in lower- and middle-income countries.