Pharmacodynamic comparison of linezolid, teicoplanin and vancomycin against clinical isolates of Staphylococcus aureus and coagulase-negative staphylococci collected from hospitals in Brazil
Pharmacodynamic comparison of linezolid, teicoplanin and vancomycin against clinical isolates of Staphylococcus aureus and coagulase-negative staphylococci collected from hospitals in Brazil
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DOI：
10.1111/j.1469-0691.2007.01885.x
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发表时间：
2008-02-01
影响因子：
14.2
通讯作者：
Nicolau, D. P.
中科院分区：
文献类型：
--
作者：
Kuti, J. L.;Kiffer, C. R. V.;Nicolau, D. P.
以曲线下的稳态总药物面积与最低抑菌浓度(MIC)的比率(AUC/MIC)衡量的药效暴露，通过对2003年至2005年从巴西医院收集的119株非重复的金黄色葡萄球菌和82株凝固酶阴性葡萄球菌(CNS)的5000名患者进行蒙特卡洛模拟而建立。药效学目标包括利奈唑胺的AUC/MIC>；82.9，替考拉宁和万古霉素的AUC/MIC>；345，以及万古霉素的免费药物AUC/MIC>；180。利奈唑胺600 mg每12h、替考拉宁400 mg每24 h、万古霉素1000 mg每12 h、万古霉素1000 mg每12 h和每8 h对所有金黄色葡萄球菌的累积有效率分别为96.0%、30.1%、71.6%、48.0%和65.1%。使用万古霉素的游离药物靶点可以将高剂量方案的CFR提高到94.6%，但对低剂量方案的结果没有实质性的改变。同一抗生素方案对所有CNS菌株的CFRS分别为97.8%、13.4%、34.6%、10.9%和31.3%。除利奈唑胺对耐甲氧西林的中枢神经系统耐药外，其余耐甲氧西林的菌株CFR均降低。敏感性分析没有改变针对这些分离株的药效学效力的最终顺序。尽管更高剂量的万古霉素和替考拉宁增加了CFR，但达到杀菌目标的可能性仍然低于利奈唑胺。大剂量万古霉素方案的结果高度依赖于所使用的药效学指标。这些数据表明，与替考拉宁和万古霉素相比，利奈唑胺对这些葡萄球菌更有可能达到其必要的药效目标。
Pharmacodynamic exposures, measured as the ratio of steady-state total drug area under the curve to MIC (AUC/MIC), were modelled using a 5000-patient Monte-Carlo simulation against 119 non-duplicate clinical isolates of Staphylococcus aureus and 82 coagulase-negative staphylococci (CNS) collected from hospitals in Brazil between 2003 and 2005. Pharmacodynamic targets included an AUC/MIC > 82.9 for linezolid and > 345 for teicoplanin and vancomycin, as well as a free drug AUC/MIC > 180 for vancomycin. The cumulative fractions of response (CFRs) against all S. aureus isolates were 96.0%, 30.1%, 71.6%, 48.0% and 65.1% for linezolid 600 mg every 12 h, teicoplanin 400 mg every 24 h and 800 mg every 24 h, and vancomycin 1000 mg every 12 h and every 8 h, respectively. Using a free drug target for vancomycin improved the CFR to 94.6% for the high-dose regimen, but did not substantially alter results for the lower dose. CFRs against all CNS isolates were 97.8%, 13.4%, 34.6%, 10.9% and 31.3%, respectively, for the same antibiotic regimens. The CFR was reduced for all compounds among the methicillin-resistant isolates, except for linezolid against methicillin-resistant CNS. Sensitivity analyses did not alter the final order of pharmacodynamic potency against these isolates. Although higher doses of vancomycin and teicoplanin increased the CFR, the likelihood of achieving bactericidal targets was still lower than with linezolid. The results for the high-dose vancomycin regimen were highly dependent on the pharmacodynamic target utilised. These data suggest that linezolid has a greater probability of attaining its requisite pharmacodynamic target than teicoplanin and vancomycin against these staphylococci.