title: Bactericidal effects of various concentrations of enrofloxacin, florfenicol, tilmicosin phosphate, and tulathromycin on clinical isolates of Mannheimia haemolytica.
abstract: OBJECTIVE
  To determine bactericidal effects of enrofloxacin, florfenicol, tilmicosin, and tulathromycin on clinical isolates of Mannheimia haemolytica at various bacterial densities and drug concentrations.
  
  
  METHODS
  4 unique isolates of M haemolytica recovered from clinically infected cattle.
  
  
  METHODS
  Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined for each drug and isolate. Mannheimia haemolytica suspensions (10(6) to 10(9) CFUs/mL) were exposed to the determined MIC and MPC and preestablished maximum serum and tissue concentrations of each drug. Log10 reduction in viable cells (percentage of cells killed) was measured at various points.
  
  
  RESULTS
  Bacterial killing at the MIC was slow and incomplete. After 2 hours of isolate exposure to the MPC and maximum serum and tissue concentrations of the tested drugs, 91% to almost 100% cell killing was achieved with enrofloxacin, compared with 8% growth to 93% cell killing with florfenicol, 199% growth to 63% cell killing with tilmicosin, and 128% growth to 43% cell killing with tulathromycin over the range of inoculum tested. For all drugs, killing of viable organisms was evident at all bacterial densities tested; however, killing was more substantial at the MPC and maximum serum and tissue drug concentrations than at the MIC and increased with duration of drug exposure. Rank order of drugs by killing potency was enrofloxacin, florfenicol, tilmicosin, and tulathromycin.
  
  
  CONCLUSIONS
  Findings suggested that antimicrobial doses that equaled or exceeded the MPC provided rapid killing of M haemolytica by the tested drugs, decreasing opportunities for antimicrobial-resistant subpopulations of bacteria to develop during drug exposure.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Blondeau
authors.forename: Shantelle D
authors.initials: SD
authors.lastname: Shebelski
authors.forename: Christine K
authors.initials: CK
authors.lastname: Hesje
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002417:Cattle; D004187:Disaccharides / Q000494:pharmacology; D000077422:Enrofloxacin; D024841:Fluoroquinolones / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000494:pharmacology; D016978:Mannheimia haemolytica / Q000187:drug effects*; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D048089:Pneumonia of Calves, Enzootic / Q000188:drug therapy* / Q000382:microbiology; D013839:Thiamphenicol / Q000031:analogs & derivatives / Q000494:pharmacology; D015645:Tylosin / Q000031:analogs & derivatives / Q000494:pharmacology; D014481:United States; D018942:Macrolides
chemical_list: D000900:Anti-Bacterial Agents; D004187:Disaccharides; D000077422:Enrofloxacin; D024841:Fluoroquinolones; D006571:Heterocyclic Compounds; D013839:Thiamphenicol; D015645:Tylosin; C035534:florfenicol; C485204:tulathromycin; D018942:Macrolides; C052319:tilmicosin