title: Pharmacodynamics of marbofloxacin for calf pneumonia pathogens.
abstract: The pharmacodynamic (PD) properties of the fluoroquinolone, marbofloxacin, were determined for the bovine respiratory tract pathogens Mannheima haemolytica and Pasteurella multocida. For six pathogenic isolates of each organism, three in vitro indices of efficacy and potency were determined, namely, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill curves. Each parameter was determined in two matrices, Mueller Hinton Broth (MHB) and calf serum. For serum, MBC:MIC ratios were 2.7:1 (M. haemolytica) and 2.4:1 (P. multocida). The killing action of marbofloxacin had the characteristics of concentration dependency against M. haemolytica and co-dependency (on time and concentration) against P. multocida. To confirm the characteristics of the time-kill profiles, growth inhibition produced by marbofloxacin was also established ex vivo in three biological fluids, calf serum, exudate and transudate, harvested from a tissue cage model. The in vitro time-kill data were modelled with pharmacokinetic properties of marbofloxacin, established by intramuscular administration in calves at a dose of 2 mg/kg; three levels of activity, namely bacteriostatic, 3 log10 reduction and 4 log10 reduction in bacterial counts were determined. Mean AUC(24h)/MIC values (with percentage coefficients of variation indicating inter-isolate variability) for M. haemolytica, based on serum MICs, were 31.3 (41.6), 57.7 (42.4) and 79.2 (44.6) h, respectively. Corresponding values for MHB were 20.5 (58.0), 40.5 (51.8) and 51.2 (24.30) h, respectively. When allowance was made for binding of marbofloxacin to serum protein, the AUC(24h)/MIC values for serum were similar to those for MHB. Numerical AUC(24h)/MIC values for P. multocida were slightly lower than those obtained for M. haemolytica. These data establish for the first time inter-isolate variability in AUC(24h)/MIC values required for three levels of bacterial kill for two pathogenic species and thereby provide an indication of variability in serum concentration that might be required to achieve efficacy in clinical subjects.
authors: The Royal Veterinary College, Hawkshead Campus, Hatfield, Hertfordshire AL9 7TA, United Kingdom.
authors: Joanna
authors: J
authors: Illambas
authors: Timothy
authors: T
authors: Potter
authors: Zhangrui
authors: Z
authors: Cheng
authors: Andrew
authors: A
authors: Rycroft
authors: John
authors: J
authors: Fishwick
authors: Peter
authors: P
authors: Lees
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D024841:Fluoroquinolones / Q000494:pharmacology*; D066298:In Vitro Techniques; D016978:Mannheimia haemolytica / Q000187:drug effects*; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D010326:Pasteurella Infections / Q000188:drug therapy / Q000662:veterinary; D016979:Pasteurella multocida / Q000187:drug effects*; D048089:Pneumonia of Calves, Enzootic / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C080260:marbofloxacin