【作者】 张涛； 李媛； 董亚琳；

【Author】 Zhang Tao;Li Yuan;Dong Yalin;Department of Pharmacy, the First Affiliated Hospital of Xi’an Jiaotong University;Department of Pharmacy, the AffiliatedChildren’s Hospital of Xi’an Jiaotong University;

【机构】 西安交通大学第一附属医院药学部； 西安市儿童医院药剂科；

【摘要】 目的:万古霉素是一种糖肽类抗生素,是临床治疗耐甲氧西林葡萄球菌感染的一线用药。儿童是一类特殊的群体,其生理状况和发育程度会随着成长出现明显差异,使得药物的药动学性质变化更为显著。尽管万古霉素说明书提供了对儿科患者的用药方案,但在多数儿科患者中均处于亚治疗浓度,且浓度变异较大。因此,本研究旨在研究影响万古霉素在儿科患者中药物浓度的因素,以促进个体化给药治疗。方法:本研究为一项多中心、回顾性研究。纳入两院自2016年10月～2018年1月由临床医生确诊和拟诊革兰氏阳性球菌引起感染,并接受万古霉素治疗大于三剂的儿科感染患者,排除局部用药或作预防性使用的患者。通过医院电子病历系统提取患者的人口学资料,疾病诊断,生理生化指标及用药情况。于下次给药前收集符合纳入标准患者的临床样本,使用LC-MS/MS测定血药浓度。将P<0.2的单因素分析结果纳入到最终的多因素分析中,探索变量与浓度间的相关性。结果:共纳入228例儿科患者,451个样本,其中男性93例,女性135例,平均年龄为2.7(±3.3)岁,平均体重为12.5(±9.9)kg,平均血药浓度为8.2(±6.0)mg/L。药物浓度达到治疗窗的患者仅有23.2%(10-20 mg/L),小于10mg/L和大于20 mg/L分别为70.6%、6.1%。纳入到最终多因素回归中的潜在因素包括年龄,体重、总蛋白、血清肌酐、脓毒症、入住ICU,结果显示体重,总蛋白,血清肌酐,脓毒症是显著影响万古霉素在儿科感染患者中血药浓度的因素:Cvan=2.11-0.006*体重-0.304*总蛋白+0.34*肌酐+0.253*脓毒症。尽管在多因素分析中未能发现年龄对血药浓度的影响,但亚组分析结果显示,新生儿的血药浓度显著高于其他年龄段儿童(10.6 VS. 7.6,P=0.03)。讨论:万古霉素血药浓度在儿科患者中达标率严重不足。患者体重,总蛋白,肌酐,是否发生脓毒症是影响万古霉素浓度的显著因素。此外,尽管本研究未发现年龄对药物浓度产生影响,但仍建议医师在提供个体化治疗的临床实践中应考虑到患者年龄。更多还原

【Abstract】 Objective Vancomycin is a glycopeptide antibiotic and the first choice of clinical treatment for methicillin-resistant Staphylococcus. Children are a special patient group with obviously different physiological and pathological characteristicsthrough their maturation, causing the variationof pharmacokinetic properties more significant. Although the vancomycin dosing regimen is provided for pediatric patients, it is at sub-therapeutic concentrations in most pediatric patients and has a large variation in concentrations. The aim of this study was to investigate the factors that influence the concentration of vancomycin in pediatric patients in order to opitimize treatment of vancomycin.MethodsCurrent study was a multicenter, retrospective study. Children who were diagnosed as infections with gram-positive bacterialby clinicians from October 2016 to January 2018, and received vancomycin for treatment more than three doses were enrolled.Patients with local infections or prophylactic were excluded.Thedataregarding demographic, disease diagnosis, physiological and biochemical indicators and medication status were extracted through the Hospital Information System. The blood samples of patients were collected prior to the next dose, and plasma concentrations were determined using LC-MS/MS. The P < 0.2 ofunivariate analysiswas included in the final multivariate analysis to explore the correlation between variables and concentrations.ResultsA total of 228 pediatric patients with 451 samples were included, including93 males and 135 females. The mean(standard deviation) of age was 2.7(±3.3) years,and the mean(standard deviation) of weight was 12.5(±9.9)kg. The mean(standard deviation) of plasma concentration was 8.2(±6.0) mg/L. Only 23.2% reached the therapeutic range(10-20 mg/L), and less than 10 mg/L and greater than 20 mg/L were70.6% and 6.1%, respectively. Potential factors included in the final multivariate regression were age, weight, total protein, serum creatinine, sepsis, admission to the ICU. The results showed body weight, total protein, serum creatinine, and sepsis were significantly correlated with vancomycin concentrations:Cvan=2.11-0.006*body weight-0.304*total protein+0.34*creatinine+0.253*sepsis.Although the effect of age on plasma concentrations could not be found in multivariate analysis, the subgroup analysis showed the concentrations of neonates were significantly higher than the rest of patients(10.6 vs. 7.6, P = 0.03).Discussion The concentration of vancomycin is seriously insufficient in the pediatric patients. Weight, total protein, creatinine, and sepsis were significant factors affecting vancomycin concentration. In addition, although the study did not find that age had an effect on drug concentration, it was still suggested that physicians should consider the patient’s age in the clinical practice of providing individualized treatment.更多还原