前瞻性研究使用谷浓度与曲线下面积来确定治疗万古霉素剂量。
Prospective Trial on the Use of Trough Concentration versus Area under the Curve To Determine Therapeutic Vancomycin Dosing.
机构信息
University of Southern California, Keck School of Medicine, Los Angeles, California, USA
Laboratory of Applied Pharmacokinetics and Bioinformatics (LAPKB), Saban Research Institute, and Division of Infectious Diseases, Children's Hospital of Los Angeles, Los Angeles, California, USA.
出版信息
Antimicrob Agents Chemother. 2018 Jan 25;62(2). doi: 10.1128/AAC.02042-17. Print 2018 Feb.
We hypothesized that dosing vancomycin to achieve trough concentrations of >15 mg/liter overdoses many adults compared to area under the concentration-time 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 ( < 0.0001). After enrollment, median trough concentrations by year were 14.4, 9.7, and 10.9 mg/liter ( = 0.005), with 36%, 7%, and 6% over 15 mg/liter ( < 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; = 0.003), shorter therapy durations (8.2, 5.4, and 4.7 days; = 0.03), and reduced nephrotoxicity (8%, 0%, and 2%; = 0.01). The median inpatient stay was 20 days among nephrotoxic patients versus 6 days ( = 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 per-patient blood sampling, and shorter length of therapy, without compromising efficacy. These benefits have the potential for substantial cost savings. (This study has been registered at ClinicalTrials.gov under registration no. NCT01932034.).
我们假设，与 AUC 指导下的剂量相比，将万古霉素的谷浓度滴定至 >15mg/L 会使许多成年人过量。我们进行了一项为期 3 年的万古霉素剂量、血浆浓度和结局的前瞻性研究。在第 1 年，非研究临床医生将目标谷浓度设定为 10-20mg/L（取决于感染情况）并控制剂量。在第 2 年和第 3 年，研究团队使用 BestDose 贝叶斯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 800mg·h/L，而不考虑谷浓度。对于 AUC 的贝叶斯估计，我们在第 1 年和第 2 年使用谷浓度样本，并在第 3 年使用最佳时间样本。我们共纳入了 252 名年龄≥18 岁且至少有 1 次万古霉素浓度可供评估的成年人。与 AUC（<0.0001）相比，只有 19%的谷浓度具有治疗作用，而 70%的 AUC 具有治疗作用（<0.0001）。入组后，每年的中位数谷浓度分别为 14.4、9.7 和 10.9mg/L（=0.005），其中 36%、7%和 6%的谷浓度超过 15mg/L（<0.0001）。第 2 年和第 3 年的贝叶斯 AUC 指导剂量与每位患者的附加血样数量减少有关（3.6、2.0 和 2.4；=0.003），治疗持续时间缩短（8.2、5.4 和 4.7 天；=0.03），肾毒性降低（8%、0%和 2%；=0.01）。肾毒性患者的中位住院时间为 20 天，而非肾毒性患者为 6 天（=0.002）。不同年份的疗效无差异，42%的患者存在微生物学证实的感染。与谷浓度目标相比，AUC 指导、贝叶斯估计辅助的万古霉素剂量与降低肾毒性、减少每位患者的采血次数以及缩短治疗时间有关，而不影响疗效。这些益处具有降低成本的潜力。（本研究已在 ClinicalTrials.gov 注册，注册号为 NCT01932034。）
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