Abstract
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.
Highlights
Antimicrobial use in food animal production has received considerable attention[8,9,10,11,12,13,14], antimicrobial resistance in equine medicine has received relatively limited attention
The purposes of the study were to directly observe and compare the impact of treatment with macrolide antimicrobial with rifampin (MaR) or Gallium maltolate (GaM) in individual foals with subclinical pneumonia – and untreated, age-matched, healthy foals without subclinical pneumonia – on: (i) the diversity of the gastrointestinal tract (GIT) microbiota, (ii) the abundance and diversity of antimicrobial resistance genes (ARGs) of GIT bacteria, (iii) the number of R. equi and Enterococccus spp. isolates in fecal swabs from foals and antimicrobial susceptibilities of these isolates
MaR treatment alters the GIT microbiota and increases the abundance and diversity of genes associated with resistance to macrolides and other antimicrobials
Summary
Antimicrobial use in food animal production has received considerable attention[8,9,10,11,12,13,14], antimicrobial resistance in equine medicine has received relatively limited attention. Observational studies have linked the emergence and environmental burden of MRRE at horse-breeding farms to increased use of MaR (as www.nature.com/scientificreports a consequence of mass antimicrobial preventive treatment of subclinical pneumonia)[17,30]. The purposes of the study were to directly observe and compare the impact of treatment with MaR or GaM in individual foals with subclinical pneumonia – and untreated, age-matched, healthy foals without subclinical pneumonia – on: (i) the diversity of the gastrointestinal tract (GIT) microbiota, (ii) the abundance and diversity of antimicrobial resistance genes (ARGs) of GIT bacteria, (iii) the number of R. equi (the pathogen targeted for treatment) and Enterococccus spp. We provide direct evidence that the common practice[41] of orally treating foals with subclinical pneumonia with MaR results in dysbiosis, increased the abundance and diversity of resistance genes in their fecal bacteria, and selected for bacteria resistant to MaR and other antimicrobials. These changes to fecal bacteria and environmental selection observed for macrolides were not observed for GaM
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