Association between antimicrobial drug class for treatment and retreatment of bovine respiratory disease (BRD) and frequency of resistant BRD pathogen isolation from veterinary diagnostic laboratory samples

PLoS One. 2019 Dec 13;14(12):e0219104. doi: 10.1371/journal.pone.0219104. eCollection 2019.

Abstract

Although 90% of BRD relapses are reported to receive retreatment with a different class of antimicrobial, studies examining the impact of antimicrobial selection (i.e. bactericidal or bacteriostatic) on retreatment outcomes and the emergence of antimicrobial resistance (AMR) are deficient in the published literature. This survey was conducted to determine the association between antimicrobial class selection for treatment and retreatment of BRD relapses on antimicrobial susceptibility of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. Pathogens were isolated from samples submitted to the Iowa State University Veterinary Diagnostic Laboratory from January 2013 to December 2015. A total of 781 isolates with corresponding animal case histories, including treatment protocols, were included in the analysis. Original susceptibility testing of these isolates for ceftiofur, danofloxacin, enrofloxacin, florfenicol, oxytetracycline, spectinomycin, tilmicosin, and tulathromycin was performed using Clinical and Laboratory Standards Institute guidelines. Data were analyzed using a Bayesian approach to evaluate whether retreatment with antimicrobials of different mechanistic classes (bactericidal or bacteriostatic) increased the probability of resistant BRD pathogen isolation in calves. The posterior distribution we calculated suggests that an increased number of treatments is associated with a greater probability of isolates resistant to at least one antimicrobial. Furthermore, the frequency of resistant BRD bacterial isolates was greater with retreatment using antimicrobials of different mechanistic classes than retreatment with the same class. Specifically, treatment protocols using a bacteriostatic drug first followed by retreatment with a bactericidal drug were associated with a higher frequency of resistant BRD pathogen isolation. In particular, first treatment with tulathromycin (bacteriostatic) followed by ceftiofur (bactericidal) was associated with the highest probability of resistant M. haemolytica among all antimicrobial combinations. These observations suggest that consideration should be given to antimicrobial pharmacodynamics when selecting drugs for retreatment of BRD. However, prospective studies are needed to determine the clinical relevance to antimicrobial stewardship programs in livestock production systems.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents / pharmacology
  • Bovine Respiratory Disease Complex / drug therapy*
  • Bovine Respiratory Disease Complex / microbiology*
  • Cattle
  • Cephalosporins
  • Disaccharides
  • Drug Resistance, Microbial / physiology*
  • Fluoroquinolones
  • Heterocyclic Compounds
  • Mannheimia haemolytica / drug effects
  • Microbial Sensitivity Tests
  • Pasteurella multocida / drug effects
  • Pasteurellaceae / drug effects
  • Prospective Studies
  • Recurrence
  • Respiratory Tract Diseases / drug therapy
  • Serogroup
  • Tylosin / analogs & derivatives

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Cephalosporins
  • Disaccharides
  • Fluoroquinolones
  • Heterocyclic Compounds
  • danofloxacin
  • ceftiofur
  • tulathromycin
  • tilmicosin
  • Tylosin

Grants and funding

Author JFC received consulting fees from Intervet-Schering Plough Animal Health (now Merck Animal Health), Bayer Animal Health, Boehringer-Ingelheim Vetmedica, Zoetis Animal Health, Midwest Veterinary Services, and Norbrook Laboratories Ltd. Author JFC is supported by the Agriculture and Food Research Initiative Competitive Grants no. 2017-67015-27124 and 2019-04991 from the USDA National Institute of Food and Agriculture and served as USDA NIFA Grant Panel Manager from 2017- 2018. AOC has received consulting fees from Bayer Animal Health. The specific roles of these authors are articulated in the 'author contributions' section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.