title: Pharmacodynamics of antimicrobials against Mycoplasma mycoides mycoides small colony, the causative agent of contagious bovine pleuropneumonia.
abstract: BACKGROUND
  Mycoplasma mycoides subspecies mycoides Small Colony (MmmSC) is the causative agent of Contagious Bovine Pleuropneumonia (CBPP), a disease of substantial economic importance in sub-Saharan Africa. Failure of vaccination to curtail spread of this disease has led to calls for evaluation of the role of antimicrobials in CBPP control. Three major classes of antimicrobial are effective against mycoplasmas, namely tetracyclines, fluoroquinolones and macrolides. Therefore, the objectives of this study were to determine the effector kinetics of oxytetracycline, danofloxacin and tulathromycin against two MmmSC field strains in artificial medium and adult bovine serum.
  
  
  METHODS
  Minimum inhibitory concentrations (MIC) were determined for oxytetracycline, danofloxacin and tulathromycin against MmmSC strains B237 and Tan8 using a macrodilution technique, and time-kill curves were constructed for various multiples of the MIC over a 24 hour period in artificial medium and serum. Data were fitted to sigmoid E(max) models to obtain 24 hour-area under curve/MIC ratios for mycoplasmastasis and, where appropriate, for mycoplasmacidal activity and virtual mycoplasmal elimination.
  
  
  RESULTS
  Minimum inhibitory concentrations against B237 were 20-fold higher, 2-fold higher and approximately 330-fold lower in serum than in artificial medium for oxytetracycline, danofloxacin and tulathromycin, respectively. Such differences were mirrored in experiments using Tan8. Oxytetracycline was mycoplasmastatic against both strains in both matrices. Danofloxacin elicited mycoplasmacidal activity against B237 and virtual elimination of Tan8; similar maximum antimycoplasmal effects were observed in artificial medium and serum. Tulathromycin effected virtual elimination of B237 but was mycoplasmastatic against Tan8 in artificial medium. However, this drug was mycoplasmastatic against both strains in the more physiologically relevant matrix of serum.
  
  
  CONCLUSIONS
  Oxytetracycline, danofloxacin and tulathromycin are all suitable candidates for further investigation as potential treatments for CBPP. This study also highlights the importance of testing drug activity in biological matrices as well as artificial media.
authors.affiliation: Royal Veterinary College, Hatfield, Hertfordshire, United Kingdom. jdmitchell@rvc.ac.uk
authors.forename: John D
authors.initials: JD
authors.lastname: Mitchell
authors.forename: Quintin A
authors.initials: QA
authors.lastname: McKellar
authors.forename: Declan J
authors.initials: DJ
authors.lastname: McKeever
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002417:Cattle; D015169:Colony Count, Microbial; D004187:Disaccharides / Q000494:pharmacology / Q000627:therapeutic use; D024841:Fluoroquinolones / Q000494:pharmacology / Q000627:therapeutic use; D006571:Heterocyclic Compounds / Q000494:pharmacology / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009176:Mycoplasma mycoides / Q000187:drug effects* / Q000254:growth & development*; D010118:Oxytetracycline / Q000494:pharmacology / Q000627:therapeutic use; D011002:Pleuropneumonia, Contagious / Q000188:drug therapy* / Q000382:microbiology*; D013997:Time Factors; D018942:Macrolides
chemical_list: D000890:Anti-Infective Agents; D004187:Disaccharides; D024841:Fluoroquinolones; D006571:Heterocyclic Compounds; D010118:Oxytetracycline; C068581:danofloxacin; C485204:tulathromycin; D018942:Macrolides