Are Vancomycin Trough Concentrations Adequate for Optimal Dosing?
Are Vancomycin Trough Concentrations Adequate for Optimal Dosing?
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DOI：
10.1128/aac.01653-13
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发表时间：
2014-01-01
影响因子：
4.9
通讯作者：
Lodise, Thomas P.
中科院分区：
文献类型：
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作者：
Neely, Michael N.;Youn, Gilmer;Lodise, Thomas P.
目前的万古霉素治疗指南建议只使用低谷浓度来管理成人金黄色葡萄球菌感染的剂量。万古霉素的疗效和毒性都可能与血药浓度-时间曲线(AUC)下的面积有关。我们收集了来自三项研究的大量样本万古霉素药代动力学数据，这些研究包括47名肾功能不同的成年人。使用R的非参数人口建模软件包Pmetrics，我们比较了从全数据集的谷底版本和峰谷耗尽版本的模型中估计的AUC，并表征了万古霉素谷值与AUC之间的关系。与完整模型相比，只有低谷和峰值-低谷耗尽的数据集低估了真实的AUC，其平均值(95%可信区间)分别为23%(11%至33%；P=0.0001)和14%(7%至19%；P<；0.0001)。相比之下，使用完整的模型作为贝叶斯先验，仅使用低谷数据可以实现97%(93%至102%；P=0.23)的准确AUC估计。基于从完整模型模拟的5000个轮廓，在肾功能正常且治疗AUC=400毫克的成年人中。对于万古霉素MIC为1毫克/升的生物体，预计约60%的低谷浓度将低于建议的严重感染最低目标15毫克/升，这可能导致不必要的剂量增加和毒性风险。我们的数据表明，在没有贝叶斯工具的情况下，根据低谷浓度调整万古霉素剂量会导致在血浆中最大限度地安全和有效地暴露药物的效果不佳，许多成年人可以有足够的低谷浓度的万古霉素AUC
The current vancomycin therapeutic guidelines recommend the use of only trough concentrations to manage the dosing of adults with Staphylococcus aureus infections. Both vancomycin efficacy and toxicity are likely to be related to the area under the plasma concentration-time curve (AUC). We assembled richly sampled vancomycin pharmacokinetic data from three studies comprising 47 adults with various levels of renal function. With Pmetrics, the nonparametric population modeling package for R, we compared AUCs estimated from models derived from trough-only and peak-trough depleted versions of the full data set and characterized the relationship between the vancomycin trough concentration and AUC. The trough-only and peak-trough depleted data sets underestimated the true AUCs compared to the full model by a mean (95% confidence interval) of 23% (11 to 33%; P = 0.0001) and 14% (7 to 19%; P < 0.0001), respectively. In contrast, using the full model as a Bayesian prior with trough-only data allowed 97% (93 to 102%; P = 0.23) accurate AUC estimation. On the basis of 5,000 profiles simulated from the full model, among adults with normal renal function and a therapeutic AUC of >= 400 mg . h/liter for an organism for which the vancomycin MIC is 1 mg/liter, approximately 60% are expected to have a trough concentration below the suggested minimum target of 15 mg/liter for serious infections, which could result in needlessly increased doses and a risk of toxicity. Our data indicate that adjustment of vancomycin doses on the basis of trough concentrations without a Bayesian tool results in poor achievement of maximally safe and effective drug exposures in plasma and that many adults can have an adequate vancomycin AUC with a trough concentration of