万古霉素治疗儿童革兰阳性球菌感染的疗效及安全性分析
Efficacy and safety of vancomycin in the treatment of infections caused by gram-positive coccus in children
何丽明 1范亚新 2闫钢风 1王一雪 1张菁 2陆国平 1陶金好1
作者信息
- 1. 复旦大学附属儿科医院重症医学科,上海 201102
- 2. 复旦大学附属华山医院抗生素研究所
- 折叠
摘要
目的 分析革兰阳性球菌感染患儿应用万古霉素治疗后的药物浓度和暴露量,以及临床疗效和安全性,为临床提供合理应用参考.方法 前瞻性收集2012年1月至2021年3月复旦大学附属儿科医院87例革兰阳性球菌感染患儿的临床和实验室资料,进行万古霉素治疗药物监测(TDM),并计算24 h药时曲线下面积(AUC0-24h)和AUC0-24h/最低抑菌浓度(AUC0-24h/MIC)指数.结果 研究纳入的患儿年龄中位数为3.60(1.20,20.00)月龄,万古霉素给药日剂量中位数为39.23(30.00,46.51)mg/kg,血药谷浓度中位数为 3.30(1.50,7.10)mg/L,在 5～15 mg/L 范围的达标率为 26.4％(23/87).AUC0 24h中位数为213(174,293)mg·h/L,AUC0-24h/MIC中位数为221(128,349),其中日剂量>60 mg/kg患儿AUC0-24h中位数≥400 mg·h/L、4UC0-24h/MIC中位数≥400,对应年龄中位数为28.50(6.85,36.00)月龄.多因素logistic分析显示谷浓度与AUC0-24h具有较好的相关性(P=0.002).所有患儿在治疗结束时临床有效率85.1％(74/87),细菌学清除率95.4％(83/87),治疗过程中无肾功能损伤发生.结论 纳入患儿万古霉素给药日剂量、血药谷浓度、AUC0-24h/MIC中位数均低于国内外推荐范围,但万古霉素低暴露量下儿童患者仍具有较好的临床和微生物学疗效.当万古霉素日剂量>60 mg/kg(对应年龄中位数 28.50 月龄)或 Cmin≥5 mg/L 时,AUC0-24h≥400 mg·h/L 及 AUC0-24h/MIC≥400 的达标率增加.
Abstract
Objective To analyze the concentration and exposure of vancomycin in children with gram-positive coccal infection,and the corresponding clinical efficacy and safety to support rational use of vancomycin in children.Methods We prospectively collected the clinical and laboratory data of 87 children with gram-positive coccal infection in the Children's Hospital of Fudan University from January 2012 to March 2021.Therapeutic drug monitoring(TDM)was conducted for vancomycin simultaneously,to acquire the data of serum through concentration(Cmin),peak concentration(Cmax),the area under the drug concentration-time curve in a 24-h interval(AUC0-24h)and the ratio ofAUC0-24h to the minimum inhibitory concentration(AUC0-24h/MIC).Results The median(P25,P75)age of the children enrolled in this study was 3.60(1.20,20.00)months.The median dose of vancomycin was 39.23(30.00,46.51)mg/kg.The median serum Cmin was 3.30(1.50,7.10)mg/L.Cmin achieved the target(5-15 mg/L)in 23 cases(26.4％).The median AUC0-24h was 213(174,293)mg·h/L and the median AUC0-24h/MIC was 221(128,349).Adaily dose of above 60 mg/kg in children could achieve the median value of AUC0-24h and AUC0-24h/MIC greater than 400,and the corresponding median age was 28.50(6.85,36.00)months.Multivariate logistic analysis showed a good correlation between Cmin and AUC0-24h(P=0.002).At the end of treatment,the clinical efficacy rate was 85.1％(74/87)and the bacterial eradication rate was 95.4％(83/87).No renal injury occurred during the treatment.Conclusions In this study,the median daily dosage,Cmin and A UC0-24h/MIC of vancomycin were below the recommended range at home and abroad.However,good clinical and microbiological efficacy were achieved in children at low vancomycin exposure.The probability of target attainment(PTA)for A UC0-24h and AUC0-24h/MIC ≥400 increased when the daily dose of vancomycin was＞60 mg/kg(corresponding to the median age of 28.50 months)or Cmin ≥ 5 mg/L.
关键词
万古霉素/治疗药物监测/药物浓度/儿童/疗效Key words
vancomycin/therapeutic drug monitoring/drug concentration/children/efficacy引用本文复制引用
基金项目
国家重点研发计划(2021YFC2701800)
国家重点研发计划(2021YFC2701805)
上海申康医院发展中心临床科技创新项目(SHDC12020106)
出版年
2024
NETL
NSTL
万方数据