title: Observations on macrolide resistance and susceptibility testing performance in field isolates collected from clinical bovine respiratory disease cases.
abstract: The objectives of this study were; first, to describe gamithromycin susceptibility of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni isolated from cattle diagnosed with bovine respiratory disease (BRD) and previously treated with either gamithromycin for control of BRD (mass medication=MM) or sham-saline injected (control=CON); second, to describe the macrolide resistance genes present in genetically typed M. haemolytica isolates; third, use whole-genome sequencing (WGS) to correlate the phenotypic resistance and genetic determinants for resistance among M. haemolytica isolates. M. haemolytica (n=276), P. multocida (n=253), and H. somni (n=78) were isolated from feedlot cattle diagnosed with BRD. Gamithromycin susceptibility was determined by broth microdilution. Whole-genome sequencing was utilized to determine the presence/absence of macrolide resistance genes and to genetically type M. haemolytica. Generalized linear mixed models were built for analysis. There was not a significant difference between MM and CON groups in regards to the likelihood of culturing a resistant isolate of M. haemolytica or P. multocida. The likelihood of culturing a resistant isolate of M. haemolytica differed significantly by state of origin in this study. A single M. haemolytica genetic subtype was associated with an over whelming majority of the observed resistance. H. somni isolation counts were low and statistical models would not converge. Phenotypic resistance was predicted with high sensitivity and specificity by WGS. Additional studies to elucidate the relationships between phenotypic expression of resistance/genetic determinants for resistance and clinical response to antimicrobials are necessary to inform judicious use of antimicrobials in the context of relieving animal disease and suffering.
authors.affiliation: Diagnostic Medicine/Pathobiology, Kansas State University College of Veterinary Medicine, Manhattan, KS, United States. Electronic address: keith@mvsinc.net.
authors.forename: Keith D
authors.initials: KD
authors.lastname: DeDonder
authors.affiliation: USDA ARS US Meat Animal Research Center, Clay Center, NE, United States.
authors.forename: Dayna M
authors.initials: DM
authors.lastname: Harhay
authors.affiliation: Clinical Sciences, Kansas State University College of Veterinary Medicine, Manhattan, KS, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Apley
authors.affiliation: Kansas State Veterinary Diagnostic Laboratory, Kansas State University College of Veterinary Medicine, Manhattan, KS, United States.
authors.forename: Brian V
authors.initials: BV
authors.lastname: Lubbers
authors.affiliation: USDA ARS US Meat Animal Research Center, Clay Center, NE, United States.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Clawson
authors.affiliation: USDA ARS US Meat Animal Research Center, Clay Center, NE, United States.
authors.forename: Gennie
authors.initials: G
authors.lastname: Schuller
authors.affiliation: USDA ARS US Meat Animal Research Center, Clay Center, NE, United States.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Harhay
authors.affiliation: Clinical Sciences, Kansas State University College of Veterinary Medicine, Manhattan, KS, United States.
authors.forename: Brad J
authors.initials: BJ
authors.lastname: White
authors.affiliation: Clinical Sciences, Kansas State University College of Veterinary Medicine, Manhattan, KS, United States.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Larson
authors.affiliation: Diagnostic Medicine/Pathobiology, Kansas State University College of Veterinary Medicine, Manhattan, KS, United States.
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Capik
authors.affiliation: Institute of Computational Comparative Medicine, Kansas State University College of Veterinary Medicine, Manhattan, KS, United States.
authors.forename: Jim E
authors.initials: JE
authors.lastname: Riviere
authors.affiliation: Biochemistry and Molecular Genetics Department, School of Medicine, University of Louisville, Louisville, KY, United States.
authors.forename: Ted
authors.initials: T
authors.lastname: Kalbfleisch
authors.affiliation: Pharmaceutical Research and Development, Merial, Duluth, GA, United States.
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Tessman
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification; D048090:Bovine Respiratory Disease Complex / Q000382:microbiology*; D002417:Cattle; D024881:Drug Resistance, Bacterial; D018942:Macrolides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; C552399:gamithromycin
keywords: Antimicrobial resistance; Bovine respiratory disease; Gamithromycin; Histophilus somni; Macrolide; Mannheimia haemolytica; Pasteurella multocida