基于模型的个体化经验性万古霉素剂量在新生儿中的应用。
Individualized Empiric Vancomycin Dosing in Neonates Using a Model-Based Approach.
机构信息
Department of Pediatrics, Stanford University, Palo Alto, California.
Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City.
出版信息
J Pediatric Infect Dis Soc. 2019 May 11;8(2):97-104. doi: 10.1093/jpids/pix109.
BACKGROUND
Vancomycin dosing in neonates is challenging because of the large variation in pharmacokinetics. Existing empiric dosing recommendations use table-based formats, within which a neonate is categorized on the basis of underlying characteristics. The ability to individualize dosing is limited because of the small number of "dose categories," and achieving narrow exposure targets is difficult. Our objective was to evaluate a model-based dosing approach (which we designated Neo-Vanco) designed to individualize empiric vancomycin dosing in neonates.
METHODS
Neo-Vanco was developed on the basis of a published, externally validated population pharmacokinetic model. Using a simulation-based methodology, individualized empiric doses that maximize the probability of attaining a 24-hour area under the curve/minimum inhibitory concentration ratio (AUC24/MIC) of >400 while minimizing troughs >20 mg/L are calculated. To evaluate the Neo-Vanco strategy, retrospective data from neonates treated with vancomycin at 2 healthcare systems were used, and empiric dose recommendations from the following 4 sources were examined: Neo-Vanco, Neofax, Red Book, and Lexicomp. Predicted AUC24 and troughs were calculated and compared.
RESULTS
Overall, 492 neonates were evaluated (median postmenstrual age, 36 weeks [5th-95th percentiles (90% range), 25-47 weeks]; median weight, 2.4 kg [90% range, 0.6-4.8 kg]). The percentage of neonates predicted to achieve an AUC24/MIC of >400 was 94% with Neo-Vanco, 18% with Neofax, 23% with Red Book, and 55% with Lexicomp (all P < .0001 vs Neo-Vanco). Predicted troughs of >20 mg/L were infrequent and similar across the dosing approaches (Neo-Vanco, 2.8%; Neofax, 1.0% [P = .03]; Red Book, 2.6% [P = .99]; and Lexicomp, 4.1% [P = .27].
CONCLUSION
A model-based dosing approach that individualizes empiric vancomycin dosing was predicted to improve achievement of target exposure levels in neonates. Prospective clinical evaluation is warranted.
背景
由于新生儿药代动力学的巨大差异，万古霉素在新生儿中的给药具有挑战性。现有的经验性给药建议使用基于表格的格式，根据潜在特征对新生儿进行分类。由于“剂量类别”数量较少，因此无法进行个体化给药，并且很难达到狭窄的暴露目标。我们的目标是评估一种基于模型的给药方法（我们称之为 Neo-Vanco），旨在对新生儿的经验性万古霉素给药进行个体化。
方法
Neo-Vanco 是在已发表的、经过外部验证的群体药代动力学模型的基础上开发的。使用基于模拟的方法，计算出最大化实现 24 小时 AUC/MIC 比值（AUC24/MIC）>400 的概率，同时最小化谷值>20 mg/L 的个体化经验性剂量。为了评估 Neo-Vanco 策略，使用来自 2 个医疗保健系统接受万古霉素治疗的新生儿的回顾性数据，并检查了以下 4 个来源的经验性剂量建议：Neo-Vanco、Neofax、Red Book 和 Lexicomp。计算并比较了预测的 AUC24 和谷值。
结果
总体而言，评估了 492 名新生儿（中位胎龄，36 周[第 5-95 百分位数（90%范围），25-47 周]；中位体重，2.4 公斤[90%范围，0.6-4.8 公斤]）。使用 Neo-Vanco 预测 AUC24/MIC>400 的新生儿比例为 94%，Neofax 为 18%，Red Book 为 23%，Lexicomp 为 55%（均<0.0001 与 Neo-Vanco 相比）。预测的谷值>20 mg/L 很少见，且在不同的给药方法之间相似（Neo-Vanco，2.8%；Neofax，1.0%[P=0.03]；Red Book，2.6%[P=0.99]；Lexicomp，4.1%[P=0.27]）。
结论
一种个体化经验性万古霉素给药的基于模型的给药方法有望提高新生儿达到目标暴露水平的能力。需要进行前瞻性临床评估。
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