Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Central Intensive Care Unit, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Int J Antimicrob Agents. 2016 Sep;48(3):259-64. doi: 10.1016/j.ijantimicag.2016.05.009. Epub 2016 Jul 5.
Several studies have demonstrated that the ideal therapeutic effect of linezolid cannot be achieved in critically ill patients with the recommended standard dosing regimen of 600 mg every 12 h (q12h). Moreover, the optimal strategy for successful treatment is still lacking. This study analysed factors influencing the efficacy of linezolid treatment and determined the target for successful treatment by logistic regression in 27 critically ill patients with staphylococcal infection who received linezolid 600 mg q12h. The results showed that only the 24-h area under the concentration-time curve to minimum inhibitory concentration (AUC24/MIC) ratio was significantly associated with staphylococcal eradication. Reaching 80% bacterial eradication required an AUC24/MIC of 120.5, defining the therapeutic target. Different dosing regimens were evaluated using Monte Carlo simulation to determine the optimal dosage strategy for linezolid. Although the probability of target attainment (PTA) was high (>99.9%) for the standard dosing regimen at MIC ≤ 1 mg/L, the PTA was almost 0 at MIC = 2 mg/L, thus the dosing regimen required adjustment. In addition, if the dosing regimen was adjusted to 600 mg every 8 h or 600 mg every 6 h, the major staphylococci (except for MRSA and MSSA) exhibited a cumulative fraction of response of >80%, showing a higher treatment success. These findings indicate that a strategy of high linezolid dosage may be needed to increase the probability of successful treatment at MIC > 1 mg/L. The role of therapeutic drug monitoring should be encouraged for optimising linezolid exposure in critically ill patients.
多项研究表明，对于接受推荐的标准剂量方案（每 12 小时 600mg，q12h）的危重症患者，利奈唑胺无法达到理想的治疗效果。此外，成功治疗的最佳策略仍然缺乏。本研究通过对 27 例接受利奈唑胺 600mg q12h 治疗的葡萄球菌感染危重症患者进行 logistic 回归分析，探讨影响利奈唑胺疗效的因素，并确定成功治疗的目标。结果表明，只有 24 小时浓度时间曲线下面积与最低抑菌浓度（AUC24/MIC）比值与葡萄球菌清除显著相关。达到 80%细菌清除率需要 AUC24/MIC 为 120.5，定义为治疗目标。通过蒙特卡罗模拟评估不同的给药方案，以确定利奈唑胺的最佳剂量策略。虽然 MIC≤1mg/L 时标准剂量方案的目标达成率（PTA）较高（>99.9%），但 MIC=2mg/L 时 PTA 几乎为 0，因此需要调整剂量方案。此外，如果将剂量方案调整为每 8 小时 600mg 或每 6 小时 600mg，主要葡萄球菌（除 MRSA 和 MSSA 外）的累积反应率>80%，显示出更高的治疗成功率。这些发现表明，在 MIC>1mg/L 时，需要采用高剂量利奈唑胺的策略来提高成功治疗的概率。应鼓励进行治疗药物监测，以优化危重症患者利奈唑胺的暴露量。
