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The practice of prophylactic administration of a macrolide antimicrobial with rifampin (MaR) to apparently healthy foals with pulmonary lesions identified by thoracic ultrasonography (i.e., subclinically pneumonic foals) is common in the United States. The practice has been associated epidemiologically with emergence of  R. equi  resistant to MaR. Here, we report direct evidence of multi-drug resistance among foals treated with MaR.  In silico  and  in vitro  analysis of the fecal microbiome and resistome of 38 subclinically pneumonic foals treated with either MaR (n = 19) or gallium maltolate (GaM; n = 19) and 19 untreated controls was performed. Treatment with MaR, but not GaM, significantly decreased fecal microbiota abundance and diversity, and expanded the abundance and diversity of antimicrobial resistance genes in feces. Soil plots experimentally infected with  Rhodococcus equi  ( R. equi ) and treated with MaR selected for MaR-resistant  R. equi , whereas MaR-susceptible  R. equi  out-competed resistant isolates in GaM-treated or untreated plots. Our results indicate that MaR use promotes multi-drug resistance in  R. equi  and commensals that are shed into their environment where they can persist and potentially infect or colonize horses and other animals.

A Common Practice of Widespread Antimicrobial Use in Horse Production Promotes Multi-Drug Resistance