Vancomycin Exposure in Patients With Methicillin-Resistant Staphylococcus aureus Bloodstream Infections: How Much Is Enough?
Vancomycin Exposure in Patients With Methicillin-Resistant Staphylococcus aureus Bloodstream Infections: How Much Is Enough?
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DOI：
10.1093/cid/ciu398
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发表时间：
2014-09-01
影响因子：
11.8
通讯作者：
McNutt, Louise-Anne
中科院分区：
文献类型：
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作者：
Lodise, Thomas P.;Drusano, George L.;McNutt, Louise-Anne
背景当代万古霉素给药方案被设计成实现曲线下面积（AUC）与最小抑制浓度（MIC）的比率>= 400。然而，缺乏临床数据支持这一目标，现有数据依赖于基于每日万古霉素剂量和估计肾功能的药代动力学公式（人口统计学药代动力学模型）来估计AUC。对接受万古霉素治疗的耐甲氧西林金黄色葡萄球菌血流感染的住院、成人、非透析患者进行队列研究，以定量评价万古霉素暴露与结局之间的关系。根据给药方案和采集的浓度，使用贝叶斯技术估计每例患者治疗第1天和第2天的万古霉素暴露特征。使用分类和回归树（CART）分析确定与失效风险增加相关的第1天和第2天暴露阈值。失败定义为30天内死亡，菌血症>= 7天，或复发。在研究期间，123例病例符合标准。对于通过肉汤微量稀释法获得的AUC/MIC和通过Etest获得的AUC/MIC，在第1天和第2天达到CART推导的阈值的患者中，失败均不太明显（绝对值约低20%）。在多变量分析中，所有CART推导的AUC/MIC暴露阈值的所有风险比均约为0.5，表明达到CART推导的AUC/MIC暴露阈值与失败率降低2倍相关。这些发现确立了治疗前2天内每日AUC/MIC比值的至关重要性。与所有观察性研究一样，这些发现应谨慎解释，并在多中心随机试验中进行验证，然后再付诸实践。
Background. Contemporary vancomycin dosing schemes are designed to achieve an area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio of >= 400. However, scant clinical data exist to support this target and available data relied on pharmacokinetic formulas based on daily vancomycin dose and estimated renal function (demographic pharmacokinetic model) to estimate AUCs.Methods. A cohort study of hospitalized, adult, nondialysis patients with methicillin-resistant Staphylococcus aureus bloodstream infections treated with vancomycin was performed to quantitatively evaluate the relationship between vancomycin exposure and outcomes. Bayesian techniques were used to estimate vancomycin exposure profile for day 1 and 2 of therapy for each patient based on their dosing schedule and collected concentrations. Classification and Regression Tree (CART) analysis was used to identify day 1 and 2 exposure thresholds associated with an increased risk of failure. Failure was defined as 30-day mortality, bacteremia was >= 7 days, or recurrence.Results. During the study period, 123 cases met criteria. Failure was uniformly less pronounced (approximately 20% less in absolute value) in patients who achieved the CART-derived day 1 and 2 thresholds for AUC/MIC by broth microdilution and AUC/MIC by Etest. In the multivariate analyses, all risk ratios were approximately 0.5 for all CART-derived AUC/MIC exposure thresholds, indicating that achievement of CART-derived AUC/MIC exposure thresholds was associated with a 2-fold decrease in failure.Conclusions. These findings establish the critical importance of daily AUC/MIC ratios during the first 2 days of therapy. As with all observational studies, these findings should be interpreted cautiously and validated in a multi-center randomized trial before adoption into practice.