Epidemiol Mikrobiol Imunol. 2020 Winter;69(4):172-180.
Pharmacotherapy in geriatric patients is challenging due to frequent multimorbidity, polypharmacy, increased risk of adverse drug effects, and altered pharmacokinetics and pharmacodynamics associated with aging. Therapeutic drug monitoring (TDM) is a dosing individualisation strategy that helps to minimise toxicity whilst maximising the efficacy of the agent. Routine TDM of vancomycin is recommended in clinical practice in order to optimise drug exposure. Guidelines by Rybak et al. from 2009 on vancomycin TDM promote monitoring of trough concentrations only, with higher target ranges for dosage adjustment. The aim of the study was to evaluate the practice of vancomycin TDM in geriatric (aged 65 ys) and non-geriatric patients, compare two methods of dosing adjustment (trough-based vs. AUC-based approach), and finally determine covariates enabling to choose an appropriate initial vancomycin maintenance dosing regimen in geriatric patients. Methods: A retrospective analysis of all vancomycin plasma concentrations determined during a five year period in patients treated with IV vancomycin in the University Hospital Olomouc was performed. Haemodialysis patients were excluded. Each trough value was compared with the guidelines by Rybak et al. and subsequently, pharmacokinetic modelling was performed to assess individual AUC24 values.
A total of 1,458 vancomycin concentrations were included, which represented 799 individual monitoring events in 380 patients. Vancomycin was most commonly prescribed for sepsis (41.6% of all patients). Pathogens with MIC > 1 mg/L were responsible for 16.7% of all infections. Initial dosing led to optimum vancomycin exposure in 37.8% of patients. Vancomycin dosage based on the guidelines by Rybak et al. from 2009 would agree with the AUC-based dosing adjustments in 65% of all monitoring events. Approximately 19.1% of trough concentrations were below the minimum target suggested by the guidelines despite the fact that their corresponding AUC24/MIC ratios were high enough ( 400), and in further 6.1% of monitoring events, the trough-only approach would fail to accurately identify supratherapeutic concentrations. Initial dosing of 1 g twice daily was prescribed to 62.9% of patients, although it would be considered as optimal only in 32.1% of all patients. For 48 % of patients in the non-geriatric cohort, higher dosing (3 to 4 g daily) would be necessary to achieve optimum vancomycin exposure, whereas for 56% of geriatric patients, lower dosage regimens (up to 1.5 g daily) would be considered optimal. The estimated glomerular filtration rate was the most significant covariate in the pharmacokinetic model enabling the construction of a dosing nomogram.
AUC-based vancomycin monitoring is superior to trough-based approach as the latter can lead to unnecessarily aggressive dosing in over a quarter of patients. A simple nomogram using the estimated glomerular filtration rate may increase the percentage of patients receiving an optimal initial vancomycin dose.
由于老年人常患有多种疾病、同时服用多种药物、发生药物不良反应的风险增加以及与衰老相关的药代动力学和药效学改变，因此老年患者的药物治疗颇具挑战性。治疗药物监测（TDM）是一种剂量个体化策略，有助于降低药物毒性，同时提高药物的疗效。为了优化药物暴露，临床实践中建议对万古霉素进行常规 TDM。2009 年，Rybak 等人制定的万古霉素 TDM 指南建议仅监测谷浓度，并为剂量调整设定了更高的目标范围。本研究的目的是评估在老年（> 65 岁）和非老年患者中万古霉素 TDM 的实践，比较两种剂量调整方法（基于谷浓度与 AUC 比值的方法），最终确定使老年患者初始万古霉素维持剂量个体化的协变量。方法：对在奥洛穆茨大学医院接受静脉万古霉素治疗的患者在五年期间所有万古霉素血药浓度进行回顾性分析。排除血液透析患者。将每个谷浓度与 Rybak 等人的指南进行比较，随后进行药代动力学建模以评估个体 AUC24 值。结果：共纳入 1458 个万古霉素浓度，代表 380 名患者中的 799 个单独监测事件。万古霉素最常用于治疗败血症（所有患者的 41.6%）。MIC > 1 mg/L 的病原体导致所有感染的 16.7%。初始剂量使 37.8%的患者获得了最佳的万古霉素暴露。基于 2009 年 Rybak 等人指南的万古霉素剂量调整与基于 AUC 的剂量调整在所有监测事件的 65%中一致。尽管相应的 AUC24/MIC 比值足够高（> 400），但仍有约 19.1%的谷浓度低于指南建议的最低目标，而在进一步的 6.1%的监测事件中，仅基于谷浓度的方法无法准确识别超治疗浓度。62.9%的患者给予 1 g，每日两次的初始剂量，但仅在 32.1%的所有患者中被认为是最佳剂量。对于非老年组的 48%的患者，需要更高的剂量（每日 3 至 4 g）才能达到最佳的万古霉素暴露，而对于 56%的老年患者，较低的剂量方案（每日 1.5 g 以下）则被认为是最佳的。估计的肾小球滤过率是药代动力学模型中最重要的协变量，能够构建剂量列线图。结论：基于 AUC 的万古霉素监测优于基于谷浓度的方法，因为后者可能导致超过四分之一的患者不必要地过度用药。使用估计肾小球滤过率的简单列线图可以提高接受最佳初始万古霉素剂量的患者比例。
