万古霉素治疗新生儿败血症的血药浓度监测和疗效及其对免疫功能的影响

doi:10.12114/j.issn.1007-9572.2018.00.169

摘要/Abstract

摘要： 目的　评价应用万古霉素治疗新生儿败血症的血药浓度监测情况、临床疗效及其对免疫功能的影响。方法　选取2015年7月—2017年1月宁波大学医学院附属医院使用万古霉素治疗败血症的住院新生儿50例作为研究对象，根据监测的万古霉素谷浓度水平，分为A组（<10 mg/L）8例、B组（10~20 mg/L）34例和C组（>20 mg/L）8例，同期另选择非感染性疾病或非免疫系统疾病的住院新生儿50例作为对照组。比较A、B、C组患儿的血药浓度、药敏试验指标、临床疗效、细菌学疗效、不良反应发生情况以及治疗前后4组免疫功能指标。应用受试者工作特征曲线下面积（AUC）评价谷浓度、峰浓度、24 h血药浓度-时间曲线下面积（AUC24）/最低抑菌浓度（MIC）预测临床疗效的效能。结果　B组、C组患儿谷浓度、峰浓度、AUC24以及AUC24/MIC均高于A组（P<0.05）；C组患儿谷浓度、峰浓度、AUC24以及AUC24/MIC高于B组（P<0.05）。A、B、C组临床疗效比较，差异无统计学意义（P>0.05）。B、C组细菌学疗效优于A组（P<0.05）。AUC24/MIC预测临床疗效的效能优于谷浓度和峰浓度（Z=4.153、4.201，P值均<0.001）。C组患儿急性肾损伤发生率高于A组和B组（P<0.05）。治疗前，A、B、C组患儿的CD3+、CD4+、CD8+比例以及IgA、IgG水平低于对照组（P<0.05），CD64+、NK细胞比例以及IgM水平高于对照组（P<0.05）；治疗后B组和C组的CD3+、CD4+、CD8+比例和IgA、IgG水平高于A组，CD64+、NK细胞比例以及IgM水平低于A组（P<0.05）；治疗后，A、B、C组患儿的免疫学指标优于本组治疗前（P<0.05）。结论　血药浓度监测在万古霉素治疗新生儿败血症中有重要作用；万古霉素谷浓度为10~20 mg/L时的疗效和安全性较好，且能够显著改善患儿的免疫功能；AUC24/MIC>391可以预测患儿的治疗结局。

关键词: 出血性败血症, 新生儿学, 万古霉素, 血药浓度

Abstract: Objective　To evaluate the blood concentration monitoring，clinical efficacy and immune function of vancomycin in the treatment of neonatal septicemia.Methods　A total of 50 sepsis infants in the treatment of vancomycin admitted to the Affiliated Hospital of Medical School of Ningbo University from July 2015 to January 2017 were divided into group A（<10 mg/L，n=8），group B（10-20 mg/L，n=34） and group C（>20 mg/L，n=8） according to the trough level of vancomycin by concentration monitoring.In the same period， 50 newborns with non infectious diseases or non immune diseases were selected as control group.Blood concentration，drug sensitivity test indicators，clinical and bacteriological efficacy，adverse reactions of group A，B，C and immune function changes before and after treatment of 4 groups were comparatively analyzed.The area under the receiver operating characteristic（ROC） curve（AUC） was used to evaluate the efficacy of trough level，peak level and AUC24/minimal inhibitory concentration（MIC）　in predicting clinical efficacy.Results　The trough levels，peak levels，AUC24，and AUC24/MIC in group B and C were significantly higher than those in group A（P<0.05）；the trough levels，peak levels，AUC24，and AUC24/MIC in group C were higher than those in group B（P<0.05）．There was no significant difference in clinical efficacy among the three groups（P>0.05），while the bacteriological efficacy in group B and group C were significantly higher than that in group A（P<0.05）．The efficacy of AUC24/MIC for predicting clinical efficacy was higher than that of trough and peak levels（Z=4.153，4.201，P<0.001，<0.001）．The incidence of acute kidney injury in group C was 37.50%，which was significantly higher than that in group A and B（0.00%，0.00%，P<0.05）．Before treatment，the proportions of CD3+，CD4+，CD8+ and IgA，IgG levels in the group A，B，and C were lower than those in the control group（P<0.05），while the proportions of CD64+ and NK cells and IgM levelin the group A，B，and C were higher than those in the control group（P <0.05）．After treatment，the proportions of CD3+，CD4+，CD8+ and IgA，the IgG levels in group B and group C were significantly higher than those in group A，and the proportions of CD64+ and NK cells，as well the level of IgM were significantly lower than those of group A（P<0.05）．After treatment，the immunological parameters of the group A，B，and C improved significantly compared with those before the treatment（P<0.05）．Conclusion　Blood concentration monitoring of vancomycin plays an important role in the treatment of neonatal septicemia；the effect and safety of trough level as 10-20 mg/L are much better and can significantly improve the immune function；the AUC24/MIC>391 can improve the outcomes of neonatal sepsis.

Key words: Hemorrhagic septicemia, Neonatology, Vancomycin, Plasma concentration

徐军,吕一枝,李志飞,等. 万古霉素治疗新生儿败血症的血药浓度监测和疗效及其对免疫功能的影响[J]. 中国全科医学, 2018, 21(33): 4109-4114. DOI: 10.12114/j.issn.1007-9572.2018.00.169.
XU Jun,LYU Yizhi,LI Zhifei, et al. Blood Concentration Monitoring，Efficacy and Immune Function of Vancomycin in Neonatal Sepsis[J]. Chinese General Practice, 2018, 21(33): 4109-4114. DOI: 10.12114/j.issn.1007-9572.2018.00.169.

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