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首页> 外文期刊>International journal of antimicrobial agents >Concentration-dependent changes in the susceptibility and killing of Staphylococcus aureus in an in vitro dynamic model that simulates normal and impaired gatifloxacin elimination
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Concentration-dependent changes in the susceptibility and killing of Staphylococcus aureus in an in vitro dynamic model that simulates normal and impaired gatifloxacin elimination

机译：在模拟正常和受损加替沙星消除的体外动态模型中，金黄色葡萄球菌敏感性和杀伤力的浓度依赖性变化

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摘要

To demonstrate the impact of normal (NEK) and impaired elimination kinetics (IEK) of gatifloxacin on its ability to protect from losses in the susceptibility of Staphylococcus aureus, a clinical isolate of methicillin-resistant S. aureus at a starting inoculum of 10(8) cfu/ml was exposed to 3 days of quinolone dosing. A series of monoexponential pharmacokinetic profiles with half-lives of 7 h (NEK) and 31 h (IEK) were simulated over 32- and 8-fold ranges of the 24 h area under the concentration-time curve (AUC(24))-to-MIC ratio, respectively. The simulated AUC(24)/MICS were designed to provide peak concentrations (C(max)s) close to the MIC, between the MIC and the mutant prevention concentration (MPC), i.e., within the mutant selection window (MSW), and above the MPC. With both NEK and IEK simulations, significant increases in MIC were observed at those AUC24/MICS that correspond to gatifloxacin concentrations within the MSW over most of the dosing interval (>25%). No such increases were observed at the smallest AUC(24)/MIC (10 h with NEK and 20 h with IEK) when the simulated C(max)s were close to the MIC, with minimal if any bacterial killing, and at the highest AUC(24)/MICS (310 and 160 h, respectively) when gatifloxacin concentrations exceeded the MPC over most of the dosing interval, with maximal antimicrobial effect. These 'protective' AUC(24)/MIC ratios correspond to 135% of the usual gatifloxacin clinical dose (400 mg IEK) and 60% of the loading and maintenance doses (400 mg, then 200 mg IEK). This study predicts different protective potentials of gatifloxacin in IEK and NEK against staphylococcal resistance and supports the MSW concept. (C) 2003 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. [References: 22]
机译：为了证明加替沙星的正常（NEK）和消除动力学（IEK）受损对加替沙星预防金黄色葡萄球菌敏感性损失的保护能力的影响，金黄色葡萄球菌是耐甲氧西林金黄色葡萄球菌的临床分离株，起始接种量为10（8）将cfu / ml暴露于3天的喹诺酮剂量。在浓度-时间曲线下（AUC（24）），在24小时区域的32倍和8倍范围内，模拟了一系列半衰期分别为7 h（NEK）和31 h（IEK）的单指数药代动力学曲线。与MIC的比例。模拟的AUC（24）/ MICS设计为在MIC与突变预防浓度（MPC）之间（即在突变选择窗口（MSW）内）提供接近MIC的峰值浓度（C（max）s）。在MPC之上。在NEK和IEK模拟中，在大多数给药间隔（> 25％）内，对应于MSW中加替沙星浓度的那些AUC24 / MICS均观察到MIC的显着增加。当模拟的C（max）接近MIC时，在最小的AUC（24）/ MIC（NEK为10h，IEK为20h）时，没有观察到这种增加，细菌杀灭最少，最高。当加替沙星浓度在大多数给药间隔内超过MPC时，AUC（24）/ MICS（分别为310和160 h）具有最大的抗菌作用。这些“保护性” AUC（24）/ MIC比值相当于常规加替沙星临床剂量（400 mg IEK）的135％和负荷量和维持剂量（400 mg，然后200 mg IEK）的60％。这项研究预测了加替沙星在IEK和NEK中对葡萄球菌耐药性的不同保护潜力，并支持MSW概念。 （C）2003年Elsevier B.V.和国际化学疗法学会。版权所有。 [参考：22]

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