蒙特卡洛模拟评价利奈唑胺静脉治疗中国成人休克患者常见革兰阳性菌感染的标准给药方案

目的：蒙特卡洛模拟评价标准给药方案（600 mg/q12h）的利奈唑胺（LIN）静脉治疗中国成人休克患者常见革兰阳性（G⁺）球菌感染的临床有效性与安全性。方法：搜集LIN静脉给药在中国成人休克患者中的群体药动学参数及其对常见G⁺球菌的最低抑菌浓度值（MIC）和其分布频率，分别以24 h血药浓度-时间曲线下面积与MIC之比（AUC_24h/MIC）和稳态最小血药浓度（C_min^SS）作为研究微生物学疗效和临床安全性的目标指数，模拟10 000例次后得到对应目标（AUC_24h/MIC ≥80，C_min^SS<7 mg·L^-1）的达标概率（PTA）。结果：对金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌和屎肠球菌，仅当MIC≤2 mg·L^-1时方可达满意抗菌活性（PTA=100%），而对肺炎链球菌，均可达满意抗菌活性（PTA=100%）；C_min^SS与协变量血小板计数呈负相关关系，当C_min^SS <7 mg·L^-1时的PTA为6.53%。结论：对于LIN静脉治疗中国成人休克患者金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌和屎肠球菌感染，当MIC≤2 mg·L^-1时，标准给药剂量能获得较好抗菌疗效，而对于肺炎链球菌感染则均可达满意抗菌活性。此类患者标准给药剂量方案下其血小板减少症风险亦较高，必要时应根据临床情况适当减量。

Use of Monte Carlo simulation to evaluate intravenous linezolid standard dosing regimen in the treatment of common gram-positive organisms in Chinese adult patients with shock

OBJECTIVE To evaluate the clinical efficacy and safety of intravenous linezolid (LIN) standard dosing regimen (600 mg/q12 h) in Chinese adult patients with shock in their treatment of common Gram-positive (G⁺) cocci utilizing Monte Carlo simulation.METHODS The population pharmacokinetic parameters of intravenous LIN in Chinese adult patients with shock and the minimum inhibitory concentration (MIC) distribution for LIN against common G⁺ cocci were collected. The ratio of the area under the 24 h curve to MIC (AUC_{24 h}/MIC) and steady state minimum plasma concentration (C_min^SS) were used as target indexes to evaluate the microbiological efficacy and clinical safety, respectively. A 10 000 times of simulation was conducted to obtain probability of target attainment (PTA) for AUC_24h/MIC ≥80 and C_min^SS < 7 mg·L^-1.RESULTS A satisfactory antibacterial activity with PTA =100% for Stapylococcus aureus, Coagulase negative Staphylococci, Enterococcus faecalis, and Enterococcus faecium could be achieved only when MIC was ≤2 mg·L^-1, and a satisfactory antibacterial activity could also be achieved with PTA =100% for Streptococcus pneumonia, no matter what the MIC was. There was a negative correlation with C_min^SS and covariate platelet count. The PTA for C_min^SS<7 mg·L^-1 was 6.53%.CONCLUSION Optimal antibacterial effect of intravenous standard dosing regimen of LIN against Stapylococcus aureus, Coagulase negative Staphylococci, Enterococcus faecalis, and Enterococcus faecium for Chinese adult patients with shock can be obtained when MIC is ≤2 mg·L^-1, while, a satisfactory antibacterial activity could also be achieved for Streptococcus pneumonia, no matter what the MIC is. Patients have high risk of LIN-induced thrombocytopenia in terms of the intravenous LIN standard dosing regimen, and dosage should be reduced appropriately according to the clinical situation when necessary.