Contagious acquisition of antimicrobial resistance is critical for explaining emergence in western Canadian...

Antimicrobial resistance (AMR) is a growing threat to the efficacy of antimicrobials in humans and animals, including those used to control bovine respiratory disease (BRD) in high-risk calves entering western Canadian feedlots. Successful mitigation strategies require an improved understanding of the epidemiology of AMR. Specifically, the relative contributions of antimicrobial use (AMU) and contagious transmission to AMR emergence in animal populations are unknown.

A stochastic, continuous-time agent-based model (ABM) was developed to explore the dynamics of population-level AMR in Mannheimia haemolytica in pens of high-risk cattle on a typical western Canadian feedlot. The model was directly informed and parameterized with proprietary data from partner veterinary practices and AMU/AMR surveillance data where possible. Hypotheses about how AMR emerges in the feedlot environment were represented by model configurations in which detectable AMR was impacted by (1) only selection arising from AMU; (2) only transmission between animals in the same pen; and (3) both AMU-linked selection and transmission. Automated calibration experiments were used to estimate unknown parameters of interest for select antimicrobial classes. Calibrated parameter values were used in a series of Monte Carlo experiments to generate simulated outputs at both the pen and feedlot levels. Key model outputs included the prevalence of AMR by class at multiple time points across the feeding period. This study compared the relative performances of these model configurations with respect to reproducing empirical AMR data.

Across all antimicrobial classes of interest, model configurations which included the potential for contagious acquisition of AMR offered stronger fits to the empirical data. Notably, sensitivity analyses demonstrated that model outputs were more robust to changes in the assumptions underscoring AMU than to those affecting the likelihood of transmission.

This study establishes a feedlot simulation tool that can be used to explore questions related to antimicrobial stewardship in the context of BRD management. The ABM stands out for its unique hierarchical depiction of AMR in a commercial feedlot and its grounding in robust epidemiological data. Future experiments will allow for both AMU-linked selection and transmission of AMR and can accommodate parameter modifications as required.