Pharmacodynamics of antimicrobials against Mycoplasma mycoides mycoides small colony, the causative agent of contagious bovine pleuropneumonia.

Pharmacodynamics of antimicrobials against Mycoplasma mycoides mycoides small colony, the causative agent of contagious bovine pleuropneumonia.
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DOI:
10.1371/journal.pone.0044158
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
McKeever DJ
McKeever DJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Mitchell JD;McKellar QA;McKeever DJ

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丝状支原体丝状亚种小菌落(MmmSC)是牛传染性胸膜肺炎(CBPP)的病原体,CBPP是撒哈拉以南非洲地区一种具有重要经济意义的疾病。疫苗接种未能遏制这种疾病的传播,导致人们呼吁评价抗菌剂在CBPP控制中的作用。三大类抗菌药物对支原体有效,即四环素类、氟喹诺酮类和大环内酯类。因此,本研究的目的是确定土霉素、达氟沙星和图拉霉素在人工培养基和成年牛血清中对两种MmmSC田间菌株的效应动力学。使用大量稀释技术测定土霉素、达氟沙星和泰拉霉素对MmmSC菌株B237和Tan 8的最小抑菌浓度(MIC),并在人工培养基和血清中构建24小时内不同MIC倍数的时间-杀灭曲线。将数据拟合至S形Emax模型,以获得支原体抑制的24小时曲线下面积/MIC比值,并在适当情况下获得杀支原体活性和虚拟支原体消除。土霉素、达氟沙星和妥拉霉素在血清中对B237的最小抑制浓度分别比在人工培养基中高20倍、2倍和约330倍。这种差异反映在使用Tan 8的实验中。土霉素对两种基质中的两种菌株均具有支原体抑制作用。达氟沙星引起对B237和Tan 8的虚拟消除支原体的活性;在人工培养基和血清中观察到类似的最大抗支原体作用。泰拉霉素实际上消除了B237,但在人工培养基中对Tan 8有支原体抑制作用。然而,该药物对血清中生理相关基质中的两种菌株均具有支原体抑制作用。土霉素、达氟沙星和泰拉霉素都适合作为CBPP的潜在治疗方法进行进一步研究。这项研究还强调了在生物基质和人工介质中测试药物活性的重要性。
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. 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 Emax models to obtain 24 hour-area under curve/MIC ratios for mycoplasmastasis and, where appropriate, for mycoplasmacidal activity and virtual mycoplasmal elimination. 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. 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.
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