In vitro pharmacodynamics of gamithromycin against Mycoplasma mycoides subspecies mycoides Small Colony
In vitro pharmacodynamics of gamithromycin against Mycoplasma mycoides subspecies mycoides Small Colony
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DOI：
10.1016/j.tvjl.2013.05.025
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发表时间：
2013-09-01
影响因子：
2.2
通讯作者：
McKeever, Dedan J.
中科院分区：
文献类型：
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作者：
Mitchell, John D.;Goh, Shan;McKeever, Dedan J.
丝状支原体（Mycoplasma mycoides Small Colony，MmmSC）是牛传染性胸膜肺炎（contagious bovine pleuropneumonia，CBPP）的病原体，在撒哈拉以南非洲造成了重大的经济损失。目前的控制依赖于效力有限的减毒活疫苗，目前正在评估将抗菌剂作为疫苗接种的替代或辅助手段。本研究的目的是确定大环内酯类抗菌剂加米霉素在人工培养基和成年牛血清中对MmmSC的体外效应动力学。此外，还确定这两种基质之间加米霉素活性的任何差异是否反映在较旧的大环内酯类药物、泰乐菌素和替米考星上。在人工培养基和血清中测定加米霉素、泰乐菌素和替米考星对MmmSC菌株B237和Tan 8的最小抑菌浓度（MIC）。在人工培养基中所有三种大环内酯类和血清中加米霉素的MIC倍数对应的浓度下构建时间-杀灭曲线。将数据拟合至S形E-max模型。通过将菌株B237暴露于10 x MIC的抗菌剂1 h并监测其后的支原体生长来确定抗生素后效应（PAE）。在接种量为10（6）cfu/mL B237时，血清中加米霉素、泰乐菌素和替米考星的MIC分别比人工培养基低64、8和64倍。Tan 8也出现了类似的模式。在人工培养基中，所有三种抗菌剂均具有支原体抑制作用，加米霉素、泰乐菌素和替米考星对8237的最大效应分别为-0.44、-0.32和-0.49 log（10）（cfu/mL）单位。泰乐菌素和替米考星引起的PAE长于加米霉素。总之，加米霉素、泰乐菌素和替米考星均显示出对MmmSC的体外疗效，代表了临床研究的潜在候选药物，以评估其对CBPP的治疗作用。(C)2013爱思唯尔有限公司保留所有权利。
Mycoplasma mycoides mycoides Small Colony (MmmSC) is the causative agent of contagious bovine pleuropneumonia (CBPP), which is responsible for major economic losses in sub-Saharan Africa. Current control relies on live attenuated vaccines, which are of limited efficacy, and antimicrobials are now being assessed as an alternative or adjunct to vaccination. The objective of this study was to determine the in vitro effector kinetics of the macrolide antimicrobial, gamithromycin, against MmmSC in artificial medium and adult bovine serum. Furthermore, it was determined if any differences in gamithromycin activity between these two matrices were mirrored by the older macrolides, tylosin and tilmicosin. Minimum inhibitory concentrations (MICs) for gamithromycin, tylosin and tilmicosin against MmmSC strains B237 and Tan8 were determined in artificial medium and serum. Time-kill curves were constructed at concentrations corresponding to multiples of the MIC for all three macrolides in artificial medium and for gamithromycin in serum. Data were fitted to sigmoid E-max models. Post-antibiotic effects (PAE) were established by exposing strain B237 to antimicrobials at 10x MIC for 1 h and monitoring mycoplasma growth thereafter.MICs for gamithromycin, tylosin and tilmicosin were 64-, 8- and 64-fold lower, respectively, in serum than in artificial medium at an inoculum size of 10(6) cfu/mL B237. A similar pattern emerged for Tan8. All three antimicrobials were mycoplasmastatic with maximum effects of -0.44, -0.32 and -0.49 log(10) (cfu/mL) units for gamithromycin, tylosin and tilmicosin, respectively, against 8237 in artificial medium. Tylosin and tilmicosin elicited longer PAEs than gamithromycin. In conclusion, gamithromycin, tylosin and tilmicosin all demonstrated in vitro efficacy against MmmSC and represent potential candidates for clinical studies to assess their therapeutic effect against CBPP. (C) 2013 Elsevier Ltd. All rights reserved.