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血液肿瘤内科住院肾功能正常儿童持续静脉输注万古霉素:优化稳态浓度给药方案的前瞻性验证

Continuous intravenous vancomycin in children with normal renal function hospitalized in hematology-oncology: prospective validation of a dosing regimen optimizing steady-state concentration.

作者信息

Hoegy Delphine, Goutelle Sylvain, Garnier Nathalie, Rénard Cécile, Faure-Conter Cécile, Bergeron Christophe, Bertrand Yves, Bleyzac Nathalie

机构信息

Institut d'Hématologie et d'Oncologie Pédiatrique, 1 Place Pr J. Renaut 69008, Lyon, France.

Hospices Civiles de Lyon, Lyon, France.

出版信息

Fundam Clin Pharmacol. 2018 Jun;32(3):323-329. doi: 10.1111/fcp.12344. Epub 2018 Mar 24.

Abstract

Continuous intravenous (IV) infusion has been shown to be the best option to administer vancomycin because of its time-dependent bactericidal activity. Available IV vancomycin dosing guidelines in pediatrics with normal renal function leads to less than 50% of patients achieving a vancomycin serum concentration (Css) in the target range (15-20 mg/L). The primary objective of this study was to prospectively validate an age-based dosing regimen in pediatric oncology-hematology. The secondary objective was to investigate the influence on Css attainment of different variables. A continuous IV dosing nomogram was built by retrospective study (2000-2010) on Bayesian dosing adjustments performed in 161 patients. This study assessed the prospective validation of this age-based nomogram and the influence on Css attainment of variables as the gender, underlying disease (oncology or hematology), and hematopoietic stem cell transplantation (HSCT) before receiving vancomycin therapy. A total of 94 patients aged from 4.3 months to 17.9 years old with normal renal function were eligible for the prospective validation. Fifty-five of those patients (58.5%) achieved the target range of vancomycin Css. There was no significant difference between age groups (P = 0.816) and no influence of gender (P = 0.500). There was a nonsignificant trend to a better target attainment in oncology patients (69.2% vs. hematology 54.4%, P = 0.142) and patients who did not undergo HSCT (63.3% vs. 33.3%, P = 0.031). This study proposed an age-based nomogram prospectively validated which near 60% of patients of each age class achieving the target range of Css.

摘要

由于万古霉素具有时间依赖性杀菌活性,持续静脉输注已被证明是给药的最佳选择。现有的儿科肾功能正常患者静脉用万古霉素给药指南导致不到50%的患者万古霉素血清浓度(Css)达到目标范围(15 - 20mg/L)。本研究的主要目的是前瞻性验证儿科肿瘤血液学中基于年龄的给药方案。次要目的是研究不同变量对Css达到情况的影响。通过对161例患者进行的贝叶斯剂量调整的回顾性研究(2000 - 2010年)建立了连续静脉给药列线图。本研究评估了该基于年龄的列线图的前瞻性验证以及万古霉素治疗前性别、基础疾病(肿瘤学或血液学)和造血干细胞移植(HSCT)等变量对Css达到情况的影响。共有94例年龄在4.3个月至17.9岁之间、肾功能正常的患者符合前瞻性验证条件。其中55例患者(58.5%)达到了万古霉素Css的目标范围。年龄组之间无显著差异(P = 0.816),性别也无影响(P = 0.500)。肿瘤患者(69.2%对血液学患者54.4%,P = 0.142)和未接受HSCT的患者(63.3%对33.3%,P = 0.031)达到目标的趋势不显著。本研究提出了一个经过前瞻性验证的基于年龄的列线图,每个年龄组近60%的患者达到Css目标范围。

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