Enriched Shotgun Sequencing to Assess the Effects of Interventions to Reduce Antimicrobial Use in Neonatal Dairy Calves

Background

Neonatal diarrhea accounts for 20%–25% of morbidity among calves, and antimicrobial drugs (AMDs) are often administered for treatment. Systematic approaches that mitigate antimicrobial use (AMU) can be effective in decreasing antimicrobial resistance (AMR).

Hypothesis/Objectives

To determine the effects of an algorithmic farm-based intervention that reduced AMU for diarrhea on the community structure of antimicrobial resistance genes (ARGs) identified in the feces of healthy dairy calves.

Animals

Thirty-one fecal dairy calf samples collected at two timepoints and farms (N = 7–8 per sampling point) were used. Samples were obtained before AMU reductions and 12 months afterward.

Methods

Target-enriched shotgun sequencing was performed to characterize all ARGs in samples. Bioinformatics processing and statistical analysis were performed using the AMR++ pipeline, MEGARes AMR database, and R.

Results

Pre-intervention comparisons showed increased relative abundances (RA) consistent with the AMU on each farm. Intra-farm results showed that on Farm 1, there were significant increases in the RA of ARGs for tetracyclines (22.1%–27.4%, q = 0.02) and fluoroquinolones (0%–0.1%, q < 0.0001) in the Post period. On Farm 2, significant decreases were seen over time in the RA of ARGs for sulfonamides (9.6%–5.1%, q = 0.006) and fluoroquinolones (0.77%–0.12%, q = 0.004).

Conclusions and Clinical Importance

Despite similar reductions in AMU on both farms, implementing an antimicrobial stewardship algorithm was associated with differing effects on and changes to the fecal resistome.