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.MethodsMinimum 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 Emax models to obtain 24 hour-area under curve/MIC ratios for mycoplasmastasis and, where appropriate, for mycoplasmacidal activity and virtual mycoplasmal elimination.ResultsMinimum 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.ConclusionsOxytetracycline, 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.
Highlights
Mycoplasma mycoides subspecies mycoides Small Colony (MmmSC) is the causative agent of Contagious Bovine Pleuropneumonia (CBPP), a major trans-boundary disease of livestock in subSaharan Africa [1] and an enduring threat to cattle in Europe
Because the composition of artificial medium differs from that of biological matrices, so that minimum inhibitory concentration (MIC) may differ between the two, we extended these studies to adult bovine serum, as a proxy for the ‘shallow biophase,’ namely plasma, interstitial fluid and well perfused tissues [15], which are the sites of most bacterial infections [16]
Minimum inhibitory concentration values obtained for danofloxacin and tulathromycin in artificial medium were comparable using microdilution and macrodilution techniques
Summary
Mycoplasma mycoides subspecies mycoides Small Colony (MmmSC) is the causative agent of Contagious Bovine Pleuropneumonia (CBPP), a major trans-boundary disease of livestock in subSaharan Africa [1] and an enduring threat to cattle in Europe. Since livestock movement patterns in Africa are complex and difficult to control [4], state veterinary services have largely relied upon the use of live attenuated vaccines, in particular the T1/44 strain, to control the disease. 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. 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
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