万古霉素治疗新生儿败血症：中国新生儿群体药代动力学模型的预测性能和临床疗效评价。
Vancomycin in neonatal sepsis: predictive performance of a Chinese neonatal population pharmacokinetic model and clinical efficacy evaluation.
机构信息
Education department, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu, China.
Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu, China.
出版信息
Eur J Hosp Pharm. 2022 Mar;29(2):101-108. doi: 10.1136/ejhpharm-2020-002479. Epub 2021 Jan 20.
BACKGROUND
In the neonatal population, individual calculation and adjustment of vancomycin (VCM) doses has been recommended based on population pharmacokinetics (PPK) methods.
OBJECTIVE
Our previous study established a Chinese neonatal VCM PPK model. The main goal of this study was to evaluate the predictive performance of this PPK model for VCM trough concentration.
METHODS
The data on neonatal severe infection patients treated with VCM were retrospectively collected. The predictive performance of this PPK model was expressed using mean prediction error (MPE), mean absolute prediction error (MAPE), sensitivity and specificity. Linear regression analysis was used to compare predicted and measured VCM concentrations. We drew the receiver operating characteristic (ROC) curve to evaluate the predictive efficacy of the ratio of area under the concentration-time curve over 24 hours to minimum inhibitory concentration (AUC/MIC) and trough concentration for clinical efficacy.
RESULTS
A total of 40 neonates with Gram-positive bacterial sepsis were included. After VCM treatment, 32 (80%) neonates were clinically cured. Eight cases were a clinical failure: the trough concentrations and AUC were lower than that of the clinical cure patients (8.70±4.30 vs 14.30±4.50 mg/L, p=0.003; 404.30±122.80 vs 515.40±131.70, p=0.037). The measured and predicted trough concentration were 11.16 (5.96, 16.53) mg/L and 10.13 (6.61, 15.73) mg/L, respectively. The MPE and MAPE were 4.62% and 13.26% (5.30%, 25.88%), respectively. The proportion of MAPE <30% in the adjusted regimen was higher than the initial regimen (89.66% vs 65.00%, p=0.039). Predictions of sensitivity and specificity by this PPK model were 88.24% and 94.29%, respectively. The coefficients of determination of linear regression analysis were 0.9171 and 0.9009 for the initial and adjusted regimen, respectively. The AUC was correlated with the trough concentration (r=0.587, p<0.001). The ROC curve indicated that the optimal cut-off points for predicting clinical efficacy were AUC/MIC >425.47 and trough concentration >9.45 mg/L.
CONCLUSION
This PPK model has good predictive performance in Chinese neonatal patients. Both AUC/MIC and trough concentration can predict the clinical efficacy of antibacterial treatment.
背景
在新生儿人群中，已经基于群体药代动力学（PPK）方法推荐对万古霉素（VCM）剂量进行个体计算和调整。
目的
我们之前的研究建立了一个中国新生儿万古霉素 PPK 模型。本研究的主要目的是评估该 PPK 模型对万古霉素谷浓度的预测性能。
方法
回顾性收集接受万古霉素治疗的新生儿严重感染患者的数据。该 PPK 模型的预测性能通过平均预测误差（MPE）、平均绝对预测误差（MAPE）、灵敏度和特异性来表示。线性回归分析用于比较预测和测量的万古霉素浓度。我们绘制了接受者操作特征（ROC）曲线，以评估 AUC/MIC 与谷浓度比值和 AUC 对临床疗效的预测效果。
结果
共纳入 40 例革兰氏阳性菌败血症新生儿。万古霉素治疗后，32 例（80%）新生儿临床治愈。8 例临床失败：谷浓度和 AUC 低于临床治愈患者（8.70±4.30 vs 14.30±4.50 mg/L，p=0.003；404.30±122.80 vs 515.40±131.70，p=0.037）。测量和预测的谷浓度分别为 11.16（5.96，16.53）mg/L 和 10.13（6.61，15.73）mg/L。MPE 和 MAPE 分别为 4.62%和 13.26%（5.30%，25.88%）。调整方案中 MAPE<30%的比例高于初始方案（89.66% vs 65.00%，p=0.039）。该 PPK 模型预测的灵敏度和特异性分别为 88.24%和 94.29%。初始和调整方案的线性回归分析的决定系数分别为 0.9171 和 0.9009。AUC 与谷浓度呈正相关（r=0.587，p<0.001）。ROC 曲线表明，预测临床疗效的最佳截断点为 AUC/MIC>425.47 和谷浓度>9.45mg/L。
结论
该 PPK 模型在中国新生儿患者中具有良好的预测性能。AUC/MIC 和谷浓度均可预测抗菌治疗的临床疗效。
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