Tulathromycin metaphylaxis increases nasopharyngeal isolation of multidrug resistant Mannheimia haemolytica in stocker heifers

William B Crosby; Brandi B Karisch; Lari M Hiott; Lee J Pinnell; Alexandra Pittman; Jonathan G Frye; Charlene R Jackson; John Dustin Loy; William B Epperson; John Blanton Jr; Sarah F Capik; Paul S Morley; Amelia R Woolums

doi:10.3389/fvets.2023.1256997

Tulathromycin metaphylaxis increases nasopharyngeal isolation of multidrug resistant Mannheimia haemolytica in stocker heifers

Front Vet Sci. 2023 Nov 20:10:1256997. doi: 10.3389/fvets.2023.1256997. eCollection 2023.

Affiliations

¹ Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, United States.
² Department of Animal and Dairy Sciences, College of Agriculture and Life Sciences, Mississippi State University, Mississippi State, MS, United States.
³ Poultry Microbiological Safety and Processing Research Unit, U.S. National Poultry Research Center, United States Department of Agriculture-Agricultural Research Service, Athens, GA, United States.
⁴ VERO Program, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, Canyon, TX, United States.
⁵ Nebraska Veterinary Diagnostic Center, School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE, United States.
⁶ Department of Animal Sciences, College of Agriculture, Purdue University, West Lafayette, IN, United States.
⁷ Tumbleweed Veterinary Services, PLLC, Amarillo, TX, United States.

Abstract

Bovine respiratory disease (BRD) is a leading cause of disease in feedlot and stocker calves with Mannheimia haemolytica (MH) as one of the most common etiologies. One of the most effective means of controlling BRD is through metaphylaxis, which involves administering antimicrobials to all animals at high risk of developing BRD. However, increasing prevalence of multidrug resistant (MDR) MH may reduce efficacy of metaphylaxis due to decreased susceptibility to drugs used for metaphylaxis. Primarily, this study aimed to determine the effect of tulathromycin metaphylaxis and subsequent BRD treatment on antimicrobial resistance (AMR) in MH isolated from stocker calves. Secondary objectives included evaluating the effect of metaphylaxis and treatment for BRD on animal health and comparing the genetic relationship of MH isolated. Crossbred beef heifers (n = 331, mean weight = 232, SD = 17.8 kg) at high risk for BRD were randomly assigned to receive tulathromycin metaphylaxis (META, n = 167) or not (NO META, n = 164). Nasopharyngeal swabs were collected for MH isolation, antimicrobial susceptibility testing and whole genome sequencing at arrival and 3 (WK3) and 10 (WK10) weeks later. Mixed-effects logistic regression was used to identify risk factors for isolation of MH and MDR MH (resistant to ≥3 antimicrobial drug classes) at 3 and 10 weeks, BRD morbidity, and crude mortality. Animals in the META group had higher odds of isolation of MDR MH at 3 weeks [OR (95% CI) = 13.08 (5-30.9), p < 0.0001] and 10 weeks [OR (95% CI) = 5.92 (1.34-26.14), p = 0.019] after arrival. There was no difference in risk of isolation of any MH (resistant or susceptible) between META and NO META groups at all timepoints. Animals in the NO META group had 3 times higher odds of being treated for BRD [WK3: OR (95% CI) = 3.07 (1.70-5.52), p = 0.0002; WK10: OR (95% CI) = 2.76 (1.59-4.80), p = 0.0002]. Antimicrobial resistance genes found within isolates were associated with integrative conjugative element (ICE) genes. Tulathromycin metaphylaxis increased risk of isolation of MDR MH and in this population, the increase in MDR MH appeared to be associated with ICE containing antimicrobial resistance genes for multiple antimicrobial classes. This may have important implications for future efficacy of antimicrobials for control and treatment of BRD.

Keywords: antimicrobial resistance; antimicrobial susceptibility; bacterial culture; beef production; bovine respiratory disease; whole genome sequencing.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Agriculture and Food Research Initiative (AFRI) 2019-67017-29111 from the USDA National Institute of Food and Agriculture, as well as the Mikell and Mary Cheek Hall Davis Endowment for Beef Cattle Health and Reproduction at the Mississippi State University College of Veterinary Medicine.