Department of Intensive Care Unit, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
Department of Intensive Care Unit, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
J Infect Chemother. 2020 May;26(5):492-497. doi: 10.1016/j.jiac.2019.12.019. Epub 2020 Jan 23.
This study was designed to investigate the characteristics and impact indicator of vancomycin pharmacokinetics in cancer patients complicated with severe pneumonia.
Fifty-seven cancer patients complicated with severe pneumonia were included in this research. Vancomycin serum trough concentrations were measured using the fluorescence polarization immunoassay (FPIA) method. The Bayesian estimator was used to calculate the pharmacokinetic parameters.
The average initial therapeutic dose of vancomycin was 15.18 ± 3.29 mg/kg (q12 h). Our study shows that vancomycin initial trough concentrations measured in cancer patients are significantly reduced (6.54 ± 3.11 mg/L; p < 0.0001) compared with the recommended standard vancomycin trough concentration (10-15 or 15-20 mg/L). Meanwhile, the clearance (CL) and volume of distribution (Vd) of vancomycin was increased significantly in cancer patients. Multivariate linear regression analysis revealed that Cys-C was the most important variable for vancomycin trough concentration (r = 0.439). The relationships between vancomycin trough concentrations and Cys-C were further evaluated after the 57 patients were grouped by cut-off point (1.44 mg/L) of the serum Cys- C levels before vancomycin was administered. Compared with group Early group (Cys-C>1.44 mg/L), Delayed group (Cys-C≤1.44 mg/L) had much lower trough concentrations. Meanwhile, CL and CLcr were significantly increased in Delayed group (Cys-C≤1.44 mg/L). Although the clinical outcomes were similar between two groups, the duration of vasoactive agent in Early group was considerably shorter compared with Delayed group (χ = 4.213; p < 0.05).
The serum trough concentration of vancomycin was significantly reduced in cancer patients complicated with severe pneumonia. Higher dosage regimen is needed to ensure clinical effectiveness. The Cys-C level measured prior to administration of vancomycin is suggested to be the most suitable parameter to predict whether vancomycin trough concentration is up to standard dosage. Especially for patients with baseline Cys-c less than 1.44 mg/L, it is more likely to need higher dosage algorithm.
本研究旨在探讨癌症合并重症肺炎患者万古霉素药代动力学的特征和影响指标。
本研究纳入了 57 例癌症合并重症肺炎患者。采用荧光偏振免疫测定（FPIA）法测定万古霉素血清谷浓度。采用贝叶斯估算器计算药代动力学参数。
万古霉素的初始治疗剂量平均为 15.18±3.29mg/kg（q12h）。我们的研究表明，与推荐的标准万古霉素谷浓度（10-15 或 15-20mg/L）相比，癌症患者的万古霉素初始谷浓度明显降低（6.54±3.11mg/L；p<0.0001）。同时，癌症患者的万古霉素清除率（CL）和分布容积（Vd）明显增加。多元线性回归分析显示，Cys-C 是万古霉素谷浓度最重要的变量（r=0.439）。在将 57 例患者根据万古霉素治疗前血清 Cys-C 水平的截止值（1.44mg/L）分组后，进一步评估了万古霉素谷浓度与 Cys-C 之间的关系。与早期组（Cys-C>1.44mg/L）相比，延迟组（Cys-C≤1.44mg/L）的谷浓度明显较低。同时，延迟组（Cys-C≤1.44mg/L）的 CL 和 CLcr 明显增加。尽管两组患者的临床结局相似，但早期组血管活性药物的持续时间明显短于延迟组（χ²=4.213；p<0.05）。
癌症合并重症肺炎患者的万古霉素血清谷浓度明显降低。需要更高的剂量方案以确保临床疗效。建议在给予万古霉素之前测量 Cys-C 水平，以预测万古霉素谷浓度是否达到标准剂量。特别是对于基线 Cys-c 小于 1.44mg/L 的患者，更有可能需要更高的剂量算法。
