Association between respiratory disease pathogens in calves near feedlot arrival with treatment for bovine respiratory disease and subsequent antimicrobial resistance status.

Introduction: This study assessed the risk of first treatment for bovine respiratory disease (BRD) given detection of nasopharyngeal bacteria (Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni) and corresponding likelihood of antimicrobial susceptibility (C/S) at two time points during the early feeding period. Relationships between C/S results and later treatment for BRD were evaluated at both the calf-level and pen-level. The association between calf-level and pen-level C/S findings during the early feeding period and subsequent C/S results at BRD treatment were also reported. Methods: Auction-sourced, recently-weaned beef calves (n = 1,599 steers) were placed in adjacent feedlot pens (8 × 100 calves) in two subsequent years. Deep nasopharyngeal (DNP) swabs were collected from all calves at time of arrival processing (1DOF) and before metaphylaxis administration with either tulathromycin or oxytetracycline, 12 days later (13DOF), and at the time of first treatment for BRD. All samples were tested for C/S. Results: Several pen-level and individual calf-level C/S measures of interest were associated with future treatment for BRD and C/S at the time of treatment. The median DOF for first BRD treatment was 24 days following tulathromycin metaphylaxis and 11 days following oxytetracycline. Overall, sampling at 13DOF resulted in the best fit for more models of subsequent treatment for BRD and C/S results at BRD treatment than for sampling at arrival. In individual calves, recovery of M. haemolytica, P. multocida, or H. somni at 13DOF was associated with subsequent treatment for BRD within 45DOF. Pen-level prevalence of Pasteurellacea bacteria with tetracycline or macrolide resistance at arrival and 13DOF were associated with detection of bacteria with antimicrobial resistance (AMR) at BRD treatment, as were individual calf results at 13DOF. Discussion: These findings suggest that the bacteria and AMR outcomes recovered from cattle near two weeks on feed can inform the prediction of future BRD risk and concurrent antimicrobial susceptibility results at time of first BRD treatment. Notably, the associations between pen-level C/S results from previous testing and corresponding findings in calves with BRD from the same pen suggested potential testing strategies to inform antimicrobial use protocols for feedlot cattle.

Variation in Pen-Level Prevalence of BRD Bacterial Pathogens and Antimicrobial Resistance Following Feedlot Arrival in Beef Calves.

Antimicrobials are crucial for treating bovine respiratory disease (BRD) in beef feedlots. Evidence is needed to support antimicrobial use (AMU) decisions, particularly in the early part of the feeding period when BRD risk is highest. The study objective was to describe changes in prevalence and antimicrobial susceptibility of BRD bacterial pathogens at feedlot processing (1 day on feed (1DOF)), 12 days later (13DOF), and for a subset at 36DOF following metaphylactic antimicrobial treatment. Mixed-origin steer calves (n = 1599) from Western Canada were managed as 16 pens of 100 calves, receiving either tulathromycin (n = 1199) or oxytetracycline (n = 400) at arrival. Deep nasopharyngeal swabs collected at all time points underwent culture and antimicrobial susceptibility testing (AST). Variability in the pen-level prevalence of bacteria and antimicrobial susceptibility profiles were observed over time, between years, and metaphylaxis options. Susceptibility to most antimicrobials was high, but resistance increased from 1DOF to 13DOF, especially for tetracyclines and macrolides. Simulation results suggested that sampling 20 to 30 calves per pen of 200 reflected the relative pen-level prevalence of the culture and AST outcomes of interest. Pen-level assessment of antimicrobial resistance early in the feeding period can inform the evaluation of AMU protocols and surveillance efforts and support antimicrobial stewardship in animal agriculture.

Evaluating the potential of third generation metagenomic sequencing for the detection of BRD pathogens and genetic determinants of antimicrobial resistance in chronically ill feedlot cattle.

BACKGROUND: Bovine respiratory disease (BRD) is an important cause of morbidity and mortality and is responsible for most of the injectable antimicrobial use in the feedlot industry. Traditional bacterial culture can be used to diagnose BRD by confirming the presence of causative pathogens and to support antimicrobial selection. However, given that bacterial culture takes up to a week and early intervention is critical for treatment success, culture has limited utility for informing rapid therapeutic decision-making. In contrast, metagenomic sequencing has the potential to quickly resolve all nucleic acid in a sample, including pathogen biomarkers and antimicrobial resistance genes. In particular, third-generation Oxford Nanopore Technology sequencing platforms provide long reads and access to raw sequencing data in real-time as it is produced, thereby reducing the time from sample collection to diagnostic answer. The purpose of this study was to compare the performance of nanopore metagenomic sequencing to traditional culture and sensitivity methods as applied to nasopharyngeal samples from segregated groups of chronically ill feedlot cattle, previously treated with antimicrobials for nonresponsive pneumonia or lameness. RESULTS: BRD pathogens were isolated from most samples and a variety of different resistance profiles were observed across isolates. The sequencing data indicated the samples were dominated by Moraxella bovoculi, Mannheimia haemolytica, Mycoplasma dispar, and Pasteurella multocida, and included a wide range of antimicrobial resistance genes (ARGs), encoding resistance for up to seven classes of antimicrobials. Genes conferring resistance to beta-lactams were the most commonly detected, while the tetH gene was detected in the most samples overall. Metagenomic sequencing detected the BRD pathogens of interest more often than did culture, but there was limited concordance between phenotypic resistance to antimicrobials and the presence of relevant ARGs. CONCLUSIONS: Metagenomic sequencing can reduce the time from sampling to results, detect pathogens missed by bacterial culture, and identify genetically encoded determinants of resistance. Increasing sequencing coverage of target organisms will be an essential component of improving the reliability of this technology, such that it can be better used for the surveillance of pathogens of interest, genetic determinants of resistance, and to inform diagnostic decisions.