Gerontology and Geriatrics, Department of Public Health and Primary Care, KU Leuven-University of Leuven, UZ Herestraat 49, Box 7003, 3000, Leuven, Belgium.
Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven-University of Leuven, Leuven, Belgium.
Drugs Aging. 2024 Sep;41(9):753-762. doi: 10.1007/s40266-024-01140-x. Epub 2024 Aug 19.
Older adults face a higher risk of vancomycin-related toxicity given their (patho)-physiological changes, making early management of supratherapeutic exposure crucial. Yet, data on vancomycin exposure in older adults is scarce. This study aims to compare vancomycin concentrations between older and younger patients, emphasizing supratherapeutic concentrations and the effect of patient characteristics.
This observational retrospective study was conducted in the University Hospital of Leuven (EC Research S65213). We analyzed early (first) vancomycin concentrations between older (≥ 75 years) and younger patients. Multivariable analyses were conducted to evaluate the association between baseline patient characteristics with supratherapeutic exposure (logistic regression), and dose-normalized concentrations (linear regression).
We included 449 patients aged ≥ 75 years (median 80) and 1609 aged < 75 years (median 61). In univariable analysis, the first-measured vancomycin concentrations were significantly higher in older adults (p < 0.001), who more frequently reached supratherapeutic concentrations (30.7% versus 21%; p < 0.001). In multivariable analysis, factors associated with supratherapeutic concentrations were decreased the estimated glomerular filtration rate calculated by using the Chronic Kidney Disease Epidemiology Collaboration equation (eGFR) [odds ratio (OR) of 0.98, confidence interval (CI) 0.97-0.98]. Supratherapeutic concentrations had inverse association with giving lower loading dose (OR of 0.59, CI 0.39-0.90), and lower maintenance dose (OR of 0.45, CI 0.26-0.77). Factors that predicted increased dose-normalized concentrations included decreased eGFR (coefficient of -0.05, CI -0.06 to -0.04), lower body weight (coefficient of -0.04, CI -0.05 to -0.03), increased blood urea nitrogen (coefficient of 0.02, CI 0.01-0.03), and delayed time to therapeutic drug monitoring (TDM) sampling (coefficient of 0.08, CI 0.06-0.09).
The absence of age as a significant factor in the multivariable analysis suggests that eGFR mediated the relationship between age and vancomycin exposure. Older adults may benefit more from vancomycin TDM.
由于老年人的（病理）生理变化，他们面临更高的万古霉素相关毒性风险，因此早期管理超治疗性暴露至关重要。然而，关于老年人万古霉素暴露的数据很少。本研究旨在比较老年和年轻患者的万古霉素浓度，重点关注超治疗性浓度以及患者特征的影响。
这是一项在鲁汶大学医院（EC Research S65213）进行的观察性回顾性研究。我们分析了老年（≥75 岁）和年轻（<75 岁）患者的早期（首次）万古霉素浓度。多变量分析用于评估基线患者特征与超治疗性暴露（逻辑回归）和剂量标准化浓度（线性回归）之间的关联。
我们纳入了 449 名≥75 岁的患者（中位数 80 岁）和 1609 名<75 岁的患者（中位数 61 岁）。在单变量分析中，老年患者的万古霉素首次测量浓度显著较高（p<0.001），且更频繁地达到超治疗性浓度（30.7%对 21%；p<0.001）。多变量分析中，与超治疗性浓度相关的因素包括使用慢性肾脏病流行病学合作组方程（eGFR）计算的估计肾小球滤过率降低（比值比[OR]为 0.98，95%置信区间[CI]为 0.97-0.98）。超治疗性浓度与给予较低的负荷剂量（OR 为 0.59，95%CI 为 0.39-0.90）和较低的维持剂量（OR 为 0.45，95%CI 为 0.26-0.77）呈负相关。预测剂量标准化浓度增加的因素包括 eGFR 降低（系数为-0.05，95%CI 为-0.06 至-0.04）、体重降低（系数为-0.04，95%CI 为-0.05 至-0.03）、血尿素氮增加（系数为 0.02，95%CI 为 0.01-0.03）和治疗药物监测（TDM）采样时间延迟（系数为 0.08，95%CI 为 0.06-0.09）。
多变量分析中年龄不是一个显著因素，这表明 eGFR 介导了年龄与万古霉素暴露之间的关系。老年患者可能从万古霉素 TDM 中获益更多。
