背景:在儿科人群中,万古霉素的谷浓度通常很难达到推荐的每标签剂量10mg/L的下限。此外,患有中性粒细胞减少症的血液病患儿更有可能降低万古霉素的暴露量,而风险因素的探索却很少。
方法:我们回顾并分析了6年期间1453例儿科血液病患者血液中万古霉素的初始谷浓度和同步细胞计数和生化参数,从2017年到2022年。
结果:在接受40mg/kg/天的剂量后,45%的入组儿童的万古霉素波谷浓度低于5mg/L,多元回归分析显示年龄(OR=0.881,95%CI0.855~0.909,P<0.001),BMI(OR=0.941,95%CI0.904~0.980,P=0.003)和肾小球滤过率(OR=1.006,95%CI1.004~1.008,P<0.001)是独立危险因素。共有79.7%的儿童肾脏清除率增加,与年龄相关的血清肌酐水平密切相关。由于BMI较高和肾小球滤过率较低,再生障碍性贫血患儿的万古霉素谷浓度高于其他血液病患儿。
结论:年龄相关的肾脏清除率增加和低BMI值导致血液系统疾病患儿万古霉素的谷浓度不理想,需要考虑长期使用环孢素和糖皮质激素的影响。
It is usually difficult for the trough concentration of vancomycin to reach the recommended lower limit of 10 mg/L per the label dose in the paediatric population. Moreover, children with haematologic diseases who suffer from neutropenia are more likely to have lower exposure of vancomycin, and the risk factors have been poorly explored.
We reviewed and analysed the initial trough concentration of vancomycin and synchronous cytometry and biochemical parameters in the blood of 1453 paediatric patients with haematologic diseases over a 6 year period, from 2017 to 2022.
Forty-five percent of the enrolled children had vancomycin trough concentrations below 5 mg/L after receiving a dose of 40 mg/kg/day, and the multiple regression showed that age (OR = 0.881, 95% CI 0.855 to 0.909, P < 0.001), BMI (OR = 0.941, 95% CI 0.904 to 0.980, P = 0.003) and the glomerular filtration rate (OR = 1.006, 95% CI 1.004 to 1.008, P < 0.001) were independent risk factors. A total of 79.7% of the children experienced augmented renal clearance, which was closely correlated to age-associated levels of serum creatinine. The vancomycin trough concentration was higher in children with aplastic anaemia than in those with other haematologic diseases due to a higher BMI and a lower glomerular filtration rate.
Age-associated augmented renal clearance and low BMI values contributed to suboptimal trough concentrations of vancomycin in children with haematologic diseases, and the effects of long-term use of cyclosporine and glucocorticoids need to be taken into account.