Switching between bacteriostatic and bactericidal antimicrobials for retreatment of bovine respiratory disease (BRD) relapses is associated with an increased frequency of resistant pathogen isolation from veterinary diagnostic laboratory submissions

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. A survey was conducted to determine the association between antimicrobial class selection for 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. In addition, the frequency of resistant M. haemolytica 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 was associated with a higher frequency of resistant BRD pathogen isolation. This effect was more profound with specific treatment combinations; tulathromycin (bacteriostatic) followed by ceftiofur (bactericidal) was associated with the highest probability of resistant isolates among all antimicrobial combinations. These findings suggest that the selection of antimicrobial mechanistic class for retreatment of BRD should be considered as part of an antimicrobial stewardship program.