title: Evaluation of antimicrobial activity against Mycoplasma mycoides subsp. mycoides Small Colony using an in vitro dynamic dilution pharmacokinetic/pharmacodynamic model.
abstract: The objectives of this study were to assess the activity of oxytetracycline (OTC), danofloxacin and tulathromycin against Mycoplasma mycoides subsp. mycoides Small Colony, the causative agent of contagious bovine pleuropneumonia, in an in vitro dynamic concentration model and to determine the concentration and/or time dependence of such activity. Time-kill assays that simulated elimination of antimicrobials from the body were performed. Initial antimicrobial concentrations corresponded to various multiples of the MIC and cultures were diluted in a stepwise fashion with either drug-free or drug-containing artificial medium to mimic administration by single-release bolus or infusion, respectively. Where appropriate, data were fitted to sigmoidal E(max) models. OTC produced no change in mycoplasma titre from the initial inoculum size, regardless of the concentration or means of drug exposure. Both danofloxacin and tulathromycin resulted in a decrease in mycoplasma titre but neither was bactericidal (99.9 % kill) over 12 h. A greater antimycoplasmal effect, defined as the change in log(10) (c.f.u. ml(-1)) over 12 h, was achieved when danofloxacin was administered as a single-release bolus, suggesting concentration-dependent activity, whereas the antimycoplasmal effect of tulathromycin was comparable following administration by single-release bolus or infusion, owing to its long half-life.
authors.affiliation: Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield AL9 7TA, UK.
authors.forename: John D
authors.initials: JD
authors.lastname: Mitchell
authors.affiliation: University of Hertfordshire, Hatfield AL10 9AB, UK.
authors.forename: Quintin A
authors.initials: QA
authors.lastname: McKellar
authors.affiliation: Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield AL9 7TA, UK.
authors.forename: Declan J
authors.initials: DJ
authors.lastname: McKeever
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001431:Bacteriological Techniques / Q000379:methods*; D003470:Culture Media; D004187:Disaccharides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009176:Mycoplasma mycoides / Q000145:classification* / Q000187:drug effects* / Q000472:pathogenicity; D010118:Oxytetracycline / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D015203:Reproducibility of Results; D013997:Time Factors; D014774:Virulence; D018942:Macrolides
chemical_list: D000900:Anti-Bacterial Agents; D003470:Culture Media; D004187:Disaccharides; D024841:Fluoroquinolones; D006571:Heterocyclic Compounds; D010118:Oxytetracycline; C068581:danofloxacin; C485204:tulathromycin; D018942:Macrolides