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急性病患儿万古霉素肾毒性的发生率及危险因素

Incidence and Risk Factors for Vancomycin Nephrotoxicity in Acutely Ill Pediatric Patients.

作者信息

Woldu Henock, Guglielmo B Joseph

机构信息

University of California, San Francisco, CA, USA.

出版信息

J Pharm Technol. 2018 Feb;34(1):9-16. doi: 10.1177/8755122517747088. Epub 2017 Dec 10.

Abstract

Particularly with the current increased vancomycin dosing trends, the true risk of the agent's nephrotoxicity is not well characterized and remains of concern. To determine the incidence of vancomycin nephrotoxicity in acutely ill hospitalized children and to secondarily characterize the risk factors for this complication. A single-center retrospective cohort study conducted at UCSF Benioff Children's Hospital from June 2012 to June 2015. Inpatients 3 months to <19 years who received intravenous vancomycin for ≥48 hours were included. The primary outcome was incidence of nephrotoxicity, defined as an increase in serum creatinine by ≥50% from baseline. Univariate and multivariate analyses were conducted to identify risk factors for vancomycin nephrotoxicity. A total of 291 patients (272 nonnephrotoxic and 19 nephrotoxic) were included in the analysis. Of the 19 patients, 12 (4.1%) were found to have moderate to severe toxicity. The median duration of therapy was 3 (3-5) and 4 (3-6) days for the group with "no nephrotoxicity" and "nephrotoxicity," respectively. The mean time for the serum creatinine to return to normal in patients with nephrotoxicity was 5.1 days. In the multivariate analysis, only final trough concentration ≥15mg/dL (odds ratio = 3.49, 95% confidence interval = 1.2-10.1; = .021) and receipt of piperacillin/tazobactam (odds ratio = 3.14, 95% confidence interval = 1.02-9.6; = .046) were significantly associated with nephrotoxicity. The rate of moderate to severe vancomycin-associated nephrotoxicity in acutely ill children is relatively uncommon and reversible. Kidney injury is associated with increased vancomycin trough concentrations and concomitant receipt of nephrotoxins, particularly piperacillin/tazobactam.

摘要

尤其是在当前万古霉素剂量增加的趋势下,该药物肾毒性的真正风险尚未得到充分描述,仍然令人担忧。目的是确定急性病住院儿童中万古霉素肾毒性的发生率,并进一步描述这种并发症的危险因素。这是一项于2012年6月至2015年6月在加州大学旧金山分校贝尼奥夫儿童医院进行的单中心回顾性队列研究。纳入了年龄在3个月至<19岁、接受静脉注射万古霉素≥48小时的住院患者。主要结局是肾毒性的发生率,定义为血清肌酐较基线水平升高≥50%。进行单因素和多因素分析以确定万古霉素肾毒性的危险因素。共有291例患者(272例无肾毒性,19例有肾毒性)纳入分析。在这19例患者中,12例(4.1%)被发现有中度至重度毒性。“无肾毒性”组和“肾毒性”组的中位治疗时间分别为3(3 - 5)天和4(3 - 6)天。肾毒性患者血清肌酐恢复正常的平均时间为5.1天。在多因素分析中,只有最终谷浓度≥15mg/dL(比值比 = 3.49,95%置信区间 = 1.2 - 10.1;P = 0.021)和接受哌拉西林/他唑巴坦(比值比 = 3.14,95%置信区间 = 1.02 - 9.6;P = 0.046)与肾毒性显著相关。急性病儿童中中度至重度万古霉素相关肾毒性的发生率相对较低且可逆转。肾损伤与万古霉素谷浓度升高以及同时使用肾毒素有关,尤其是哌拉西林/他唑巴坦。

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