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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Time inside the mutant selection window as a predictor of staphylococcal resistance to linezolid
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Time inside the mutant selection window as a predictor of staphylococcal resistance to linezolid

机译：突变选择窗口内的时间作为葡萄球菌对线唑的预测值

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To explore if the time inside the mutant selection window (T-MSW) is a reliable predictor of emergence of bacterial resistance to linezolid, mixed inocula of each of three methicillin-resistant Staphylococcus aureus strains (MIC of linezolid 2 mu g ml(-1)) and their previously selected resistant mutants (MIC 8 mu g ml(-1)) were exposed to linezolid pharmacokinetics using an in vitro dynamic model. In five-day treatments simulated over a wide range of the 24-h area under the concentration-time curve (AUC(24)) to the MIC ratio, mutants resistant to 4 x MIC of antibiotic were enriched in a T-MSW-dependent manner. With each strain, T-MSW relationships with the area under the bacterial mutant concentration-time curve (AUBC(M)) exhibited a hysteresis loop, with the upper portion corresponding to the time above the mutant prevention concentration (MPC; T-MPC) of 0 and the lower portion-to the T-(MPC) 0. Using AUBC(M) related to the maximal value observed with a given strain (normalized AUBC(M)) at T-MPC 0, a strain-independent sigmoid relationship was established between AUBC(M) and T-MSW, as well as T-(MPC) (r(2) 0.99 for both). AUC(24)/MIC and AUC(24)/MPC relationships with normalized AUBC(M) for combined data on the three studied S. aureus strains were bell-shaped (r(2) 0.85 and 0.80, respectively). These findings suggest that T-MSW at T-(MPC) 0, T-MPC, AUC(24)/MIC and AUC(24)/MPC are useful bacterial strain-independent predictors of the emergence of staphylococcal resistance to linezolid.
机译：为了探索突变选择窗口（T-MSW）内的时间是细菌抗性的可靠预测因子，对Linezolid的含量，每种耐三种甲氧西林金黄色葡萄球菌菌株中的每种混合的接种物（Linezolid2μgml的MIC（-1 ））和其先前选择的抗性突变体（MIC8μgml（-1））使用体外动态模型暴露于Linezolid药代动力学。在浓度 - 时间曲线（AUC（24））下模拟的五天处理在浓度 - 时间曲线（AUC（24））上，富含抗生素4×MIC的突变体在T-MSW依赖性中富集方式。对于每种菌株，与细菌突变浓度 - 时间曲线（AubC（M））下的区域的T-MSW关系表现出滞后环，上部对应于突变预防浓度（MPC; T-和GT; MPC）0和下部 - T-和GT;（MPC）＆GT; 0.使用与给定菌株观察到的最大值相关的AUBC（M）（归一化AUBC（M））在T-＆ MPC＆GT; 0，在AUBC（M）和T-MSW之间以及T-（MPC）（r（2）0.99之间建立应变无关的乙状结关系。 AUC（24）/ MIC和AUC（24）/ MPC与标准化AUBC（M）的关系，用于三个研究的S.UUREUS菌株的组合数据分别为钟形（R（2）0.85和0.80）。这些研究结果表明T-＆（MPC）＆GT; 0，T-和GT; MPC，AUC（24）/ MIC和AUC（24）/ MPC是有用的细菌应变自定义因子，其出现葡萄球菌对LINZOLID的出现。

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