新生儿万古霉素血药浓度与不良反应分析

摘要/Abstract

摘要： 目的探讨新生儿万古霉素不良反应发生与血药浓度之间的关系，为临床合理用药提供依据。方法收集170例使用万古霉素治疗并进行血药浓度监测的新生儿病例资料，观察记录肝肾损害、听力损害发生的例数，分析<5 mg·L^-1、5~10 mg·L^-1、>10 mg·L^-1 3个不同血药浓度与不良反应发生的相关性。结果新生儿万古霉素平均谷浓度为（4.96±2.35）mg·L^-1，峰浓度平均为（31.04±10.13）mg·L^-1。不良反应总发生率为17.65%（30/170例），主要表现为肝损害（10.00%，17/170例）及听力损害（7.06%，12/170例），还发生1例肾损害。肝损害、听力损害的发生率明显高于肾损害的发生率（χ²=18.162，P=0.000；χ²=12.795，P=0.000）。不同血药浓度组（<5 mg·L^-1、5~10 mg·L^-1、>10 mg·L^-1）的不良反应发生率分别为16.81%（19/113例）、17.50%（7/40例）、23.53%（4/17例），组间比较无统计学意义（χ²=0.968，P=0.253），且不良反应发生率不随血药浓度增加而增大（Z=0.941，P=0.226）。万古霉素用药前后肝肾功能指标（丙氨酸氨基转移酶、尿酸、尿素氮、肌酐）比较差异均有统计学意义（均P<0.05），但各指标平均值均处于正常值范围，因而不具有临床意义。结论新生儿应用万古霉素治疗有较高的肝损害及听力损害发生率，还可发生肾损害，万古霉素不良反应发生与其血药浓度无相关性。

关键词: 万古霉素, 新生儿, 不良反应, 肝损害, 血药浓度

Abstract: Objective To investigate the relationship between vancomycin plasma concentration and drug adverse reactions in neonates, provide a basis for the rational use of vancomycin in clinical practice. Methods One hundred and seventy neonates treated with vancomycin were recruited, and their plasma levels were monitored. The number of patients who had liver, kidney and hearing damage after treatment was observed and calculated. The correlations between three different plasma levels (<5 mg·L^-1, 5~10 mg·L^-1 and >10 mg·L^-1) and adverse reactions were analyzed. Results The mean minimum, maximum level of vancomycin in serum was 4.96±2.35 mg·L^-1 and 31.04±10.13 mg·L^-1. The total incidence of adverse reactions was 17.65% (30/170 cases), the main adverse reactions included liver damage (10.00%, 17/170 cases) and hearing impairment (7.06%, 12/170 cases), one case showed renal injury. The incidence of renal injury was significantly lower than that of the liver damage and hearing impairment (χ²=18.162, P=0.000；χ²=12.795, P=0.000). The adverse reaction ratio among three different plasma levels (<5 mg·L^-1, 5~10 mg·L^-1 and >10 mg·L^-1) was 16.81% (19/113 cases), 17.50% (7/40 cases) and 23.53% (4/17 cases), respectively. There was no significant difference between the serum concentrations and adverse reaction ratio (χ²=0.968, P=0.253). Moreover, the adverse reaction rates didn’t increase along with the serum levels of vancomycin (Z=0.941, P=0.226). The parameters of liver and kidney function (alanine transaminase, urea nitrogen, creatinine, uric acid) varied significantly after vancomycin treatment (P<0.05), but there was no clinical significance because the mean values were in normal range. Conclusion Neonates treated with vancomycin have relatively high ratio of the liver damage and hearing impairment, renal injury also takes place possibly. There is no significant correlation between vancomycin plasma level and adverse reactions in neonates.

Key words: vancomycin, neonate, adverse reaction, liver damage, plasma concentration

中图分类号:

R994.11

郭雪松, 肖凤. 新生儿万古霉素血药浓度与不良反应分析[J]. 中国药物警戒, 2016, 13(7): 414-416.

GUO Xue-song, XIAO Feng . Analysis of Vancomycin Plasma Level and Adverse Reactions in Neonates[J]. Chinese Journal of Pharmacovigilance, 2016, 13(7): 414-416.

参考文献

[1] Rybak M, Lomaestro B, Rotschafer J C, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists[J]. Am J Health-Syst Pharm, 2009, 66(1) : 82-98.
[2] Kací?ová I, Grundmann M. Therapeutic monitoring of vancomycin in routine clinical practice[J]. Vnitr Lek, 2014, 60(10) : 846-851.
[3] Minne L, Eslami S, Kuiper R A, et al. Five years of therapeutic drug monitoring in the intensive care did not change vancomycin prescription behaviour: perceived needs for decision support[J]. Minerva Anestesiol, 2012, 78(6) : 684-692.
[4] Liu C, Bayer A, Cosgrove S E, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children[J]. Clin Infect Dis, 2011, 52(3) : e18-e55.
[5] Ye Z K, Tang H L, Zhai S D. Benefits of therapeutic drug monitoring of vancomycin: a systematic review and meta-analysis[J]. Plos One, 2013, 8(10) : e77169.
[6] 唐晓辉. 新生儿万古霉素血药浓度监测与不良反应分析[J]. 临床药物治疗杂志, 2015, 13(4) : 61-64.
[7] Tang L. Clinical Effect and Therapeutic Drug Monitoring of Vancomycin Treatment on Neonatal Bacterial Sepsis[J]. Value Health, 2015, 18(3) : A230.
[8] Fontana R J, Watkins P B, Bonkovsky H L, et al. Drug-induced liver injury network (DILIN) prospective study[J]. Drug Saf , 2009, 32(1) : 55-68.
[9] Mehta R L, Kellum J A, Shah S V, et al. Acute Kidney Injury Network:report of an initiative to improve outcomes in acute kidney injury[J]. Crit Care, 2007, 11(2) : R31.
[10] 戴志凌, 马莎, 韦玮, 等. 114例万古霉素的临床应用评价分析[J]. 中国药业, 2015, 24(15) : 64-65.
[11] 刘治军,胡欣.万古霉素治疗药物监测和临床应用相关指南解读[J].药品评价,2011, 8(8) : 18-23.
[12] 唐莲, 王三南, 李静静, 等. 万古霉素治疗新生儿败血症的血药浓度监测和疗效分析[J]. 药学服务与研究, 2016, 16(1): 29-33.
[13] Jacqz-Aigrain E, Leroux S, Zhao W, et al. How to use vancomycin optimally in neonates: remaining questions[J]. Expert Rev Clin Phar, 2015, 8(5) : 635-648.
[14] 李媛. 278例儿童万古霉素临床用药合理性分析[J]. 儿科药学杂志, 2015, 21(10) : 43-45.
[15] 高萍, 张华年, 陈渝军, 等. 万古霉素在患儿治疗中给药剂量与谷浓度的评估[J]. 中华医院感染学杂志, 2016, 26(6) : 1 393-1 396.
[16] 周敬凯, 张媞, 邹佳运, 等. 万古霉素血药浓度监测及儿童用药评价[J]. 实用药物与临床, 2014, 17(10) : 1 306-1 309.
[17] 张海燕, 朱春香, 罗万慰, 等. 万古霉素相关急性肾损伤的危险因素分析[J]. 中国医院药学杂志, 2016, 36(6) : 503-507.