73例白血病侵袭性肺部真菌感染患儿伏立康唑血药浓度监测结果分析

Analysis of Voriconazole Plasma Concentration Monitoring Results in 73 Children with Leukemia Invasive Pulmonary Fungal Infection

目的:分析白血病侵袭性肺部真菌感染(IPFI)患儿伏立康唑血药浓度监测结果。方法:回顾性抽取2018年12月—2023年12月我院73例白血病IPFI患儿作为研究对象,均接受伏立康唑静脉给药、口服给药治疗,统计其临床资料,了解伏立康唑血药浓度变化,并对其结果进行分析。结果:73例患儿测定伏立康唑浓度中位值为0.805μg/ml,其中55份浓度<伏立康唑目标浓度范围,46份浓度达到伏立康唑目标浓度范围,有2份浓度>伏立康唑目标浓度范围;与年龄≥6岁患儿相比,年龄<6岁的患儿谷浓度想达到设定范围,需给予更高剂量的伏立康唑,分别为4.60 mg/(kg·次)、6.32 mg/(kg·次);谷浓度<1μg/ml的血样无效治疗率高于有效治疗率,但差异无统计学意义(P>0.05);有6例患儿治疗过程中监测伏立康唑谷浓度<1μg/ml,且治疗效果欠佳;2例伏立康唑谷浓度≥5.5μg/ml的患儿出现肝功能异常。结论:开展白血病IPFI患儿伏立康唑血药浓度监测,不仅能保证用药安全性、有效性,还能为我国制定儿童伏立康唑治疗方案提供研究数据,而白血病IPFI患儿在伏立康唑常规推荐剂量下难以达到有效血药浓度,需给予更高剂量,本研究推荐年龄<6岁患儿可给予6.32mg/(kg·次)的剂量,年龄>6岁可给予4.60 mg/(kg·次)的剂量。

Objective:To analyze the monitoring results of voriconazole blood concentration in children with invasive pulmonary fungal infection(IPFI)of leukemia.Methods:From December 2018 to December 2023,73 children with leukemia IPFI in our hospital were retrospectively selected as the research objects.All of them received intravenous and oral administration of voriconazole.The clinical data were counted,the changes of voriconazole blood concentration were understood,and the results were analyzed.Results:The median voriconazole concentration of 73 children was 0.805μg/ml,of which 55 were lower than the target voriconazole concentration range,46 were within the target voriconazole concentration range,and 2 were higher than the target voriconazole concentration range.Compared with children≥6 years old,children<6 years old need to be given higher doses of voriconazole 4.60 mg/(kg·times)and 6.32 mg/(kg·times)to reach the set valley concentration range,respectively.The rate of ineffective treatment was higher than that of effective treatment in blood samples with valley concentration<1μg/ml,but the difference was not statistically significant(P>0.05).There were 6 children with voriconazole valley concentration<1μg/ml during treatment,and the therapeutic effect was not good.Two children with voriconazole valley concentration≥5.5μg/ml had abnormal liver function.Conclusion:The monitoring of plasma voriconazole concentration in children with leukemia IPFI can not only ensure the safety and effectiveness of medication,but also provide research data for the formulation of pediatric voriconazole treatment plan in China.However,it is difficult for children with leukemia IPFI to achieve effective plasma concentration under the routine recommended dose of voriconazole,and a higher dose is required.This study recommended a dose of 6.32 mg/(kg·times)for children<6 years old and 4.60 mg/(kg·times)for children>6 years old.