Prospective Trial on the Use of Trough Concentration versus Area under the Curve To Determine Therapeutic Vancomycin Dosing
Prospective Trial on the Use of Trough Concentration versus Area under the Curve To Determine Therapeutic Vancomycin Dosing
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DOI：
10.1128/aac.02042-17
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发表时间：
2018-02-01
影响因子：
4.9
通讯作者：
Minejima, Emi
中科院分区：
文献类型：
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作者：
Neely, Michael N.;Kato, Lauren;Minejima, Emi
我们假设，与浓度-时间曲线下面积（AUC）指导给药相比，万古霉素给药达到>15 mg/L的谷浓度使许多成人过量。我们进行了一项为期3年的前瞻性研究，研究万古霉素的剂量、血药浓度和结局。在第1年，非研究临床医生的目标谷浓度为10至20 mg/L（感染依赖性）和控制剂量。在第2年和第3年，研究小组使用BestDose Bayesian软件控制万古霉素剂量，以实现每日稳态AUC/MIC比值>= 400，最大AUC值为800 mg。h/L，与谷浓度无关。对于AUC的贝叶斯估计，我们在第1年和第2年使用谷值样本，在第3年使用最佳时间样本。我们招募了252名年龄>18岁、万古霉素浓度>= 1的成人。所有谷浓度中只有19%是治疗性的，而AUC中有70%是治疗性的（P < 0.0001）。入组后，各年的中位谷浓度分别为14.4、9.7和10.9 mg/L（P = 0.005），36%、7%和6%的患者超过15 mg/L（P < 0.0001）。第2年和第3年的贝叶斯AUC指导给药与每例受试者的额外血样较少（3.6、2.0和2.4; P = 0.003）、治疗持续时间较短（8.2、5.4和4.7天; P = 0.03）和肾毒性降低（8%、0%和2%; P = 0.01）相关。肾毒性患者的中位住院时间为20天，而非6天（P = 0.002）。每年的疗效没有差异，42%的患者有微生物学证实的感染。与谷浓度目标相比，AUC指导的贝叶斯估计辅助万古霉素给药与肾毒性降低、每例患者血液采样减少和治疗时间缩短相关，而不影响疗效。这些好处有可能节省大量费用。
We hypothesized that dosing vancomycin to achieve trough concentrations of >15 mg/liter overdoses many adults compared to area under the concentrationtime curve (AUC)-guided dosing. We conducted a 3-year, prospective study of vancomycin dosing, plasma concentrations, and outcomes. In year 1, nonstudy clinicians targeted trough concentrations of 10 to 20 mg/liter (infection dependent) and controlled dosing. In years 2 and 3, the study team controlled vancomycin dosing with BestDose Bayesian software to achieve a daily, steady-state AUC/MIC ratio of >= 400, with a maximum AUC value of 800 mg . h/liter, regardless of trough concentration. For Bayesian estimation of AUCs, we used trough samples in years 1 and 2 and optimally timed samples in year 3. We enrolled 252 adults who were >18 years old with >= 1 available vancomycin concentration. Only 19% of all trough concentrations were therapeutic versus 70% of AUCs (P < 0.0001). After enrollment, median trough concentrations by year were 14.4, 9.7, and 10.9 mg/liter (P = 0.005), with 36%, 7%, and 6% over 15 mg/liter (P < 0.0001). Bayesian AUC-guided dosing in years 2 and 3 was associated with fewer additional blood samples per subject (3.6, 2.0, and 2.4; P = 0.003), shorter therapy durations (8.2, 5.4, and 4.7 days; P = 0.03), and reduced nephrotoxicity (8%, 0%, and 2%; P = 0.01). The median inpatient stay was 20 days among nephrotoxic patients versus 6 days (P = 0.002). There was no difference in efficacy by year, with 42% of patients having microbiologically proven infections. Compared to trough concentration targets, AUC-guided, Bayesian estimation-assisted vancomycin dosing was associated with decreased nephrotoxicity, reduced perpatient blood sampling, and shorter length of therapy, without compromising efficacy. These benefits have the potential for substantial cost savings.