Impact of Sampling Strategy and Population Model on Bayesian Estimates of Vancomycin AUC in Patients with BMI > 40 kg/m2: A Single-Center Retrospective Study.

Sarah A Ekkelboom, Soraya M Hobart, Laurie J Barten, Staci L Hemmer
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Abstract

Background/Objectives: Growing evidence supports the use of a single trough concentration, rather than both a peak and trough, to estimate the 24 h area under the curve (AUC24) of vancomycin using Bayesian software (InsightRx® Ver.1.71). However, patients with body mass index (BMI) ≥ 40 kg/m2 are underrepresented in validation studies. Studies in patients with obesity have produced mixed results, potentially because of different population models used. Methods: This single-center, retrospective study evaluated adult inpatients with BMI ≥ 40 kg/m2. Steady-state AUC24 estimates generated by Bayesian software using both two-concentration and one-concentration inputs were compared. Agreement was defined as a percent difference within ±20%. Subgroup analyses were conducted for patients with defined peak and trough concentrations and for comparisons between two Bayesian population models (Carreno vs. Hughes). Linear regression assessed covariates associated with percent difference. Results: Among 82 encounters, 97.5% of one-concentration estimates based on the smaller concentration were within ±20% of the two-concentration AUC24,SS (mean difference: 2.9%, 95% CI: 0.14 to 3.8%). Similar agreement was observed using the larger concentration (97.5%, mean difference: -3.1%, 95% CI: -4.7 to -0.1.5%). Subgroup analysis for encounters with true peak/trough levels (n = 22) also showed 100% agreement within ±20%. The percent difference did not correlate with BMI or other covariates. Comparison of Hughes vs. Carreno models showed larger variability (only 59.1% within ±20%). Conclusions: In patients with BMI ≥ 40 kg/m2, Bayesian AUC24,SS estimation using a single vancomycin concentration is feasible. Greater caution is warranted in the setting of acute kidney injury, poor model fit, or targeting AUC at the extremes of the therapeutic range. The population model used to generate the Bayesian AUC estimate has a much greater influence than the number of concentrations analyzed. Furthermore, measuring two concentrations does not ensure concordance between models.

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抽样策略和群体模型对体重指数bb0 ~ 40kg /m2患者万古霉素AUC贝叶斯估计的影响:一项单中心回顾性研究
背景/目的:越来越多的证据支持使用贝叶斯软件(InsightRx®ver1.71)来估计万古霉素的24 h曲线下面积(AUC24),而不是同时使用峰谷浓度。然而,体重指数(BMI)≥40 kg/m2的患者在验证研究中代表性不足。对肥胖患者的研究产生了不同的结果,可能是因为使用了不同的人群模型。方法:该单中心回顾性研究评估BMI≥40 kg/m2的成年住院患者。比较了贝叶斯软件使用两种浓度和一种浓度输入产生的稳态AUC24估计。一致性定义为在±20%以内的百分比差异。对确定浓度峰谷的患者进行亚组分析,并比较两种贝叶斯总体模型(Carreno vs. Hughes)。线性回归评估与百分比差异相关的协变量。结果:在82次接触中,97.5%的基于较小浓度的单浓度估计值在两浓度AUC24,SS的±20%以内(平均差值:2.9%,95% CI: 0.14 ~ 3.8%)。使用较大浓度时,也观察到类似的一致性(97.5%,平均差异:-3.1%,95% CI: -4.7至-0.1.5%)。亚组分析对真实峰/谷水平的遭遇(n = 22)也显示在±20%以内的一致性为100%。百分比差异与BMI或其他协变量无关。Hughes与Carreno模型的比较显示出更大的变异性(在±20%范围内仅为59.1%)。结论:对于BMI≥40 kg/m2的患者,使用单一万古霉素浓度进行贝叶斯AUC24、SS估计是可行的。在急性肾损伤、模型拟合差或在治疗范围的极端情况下靶向AUC的情况下,需要更加谨慎。用于生成贝叶斯AUC估计的种群模型比所分析的浓度数量具有更大的影响。此外,测量两种浓度并不能保证模型之间的一致性。
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