伏立康唑治疗多发性骨髓瘤并发侵袭性真菌感染效果与CYP2C19基因多态性的关系  

Effect of voriconazole on treatment of multiple myeloma patients complicated with invasive fungal infection and its association with polymorphism of CYP2C19 gene

作　　者：赵小强[1] 汤平[2] 杨海平[1] 吴雅莉 仝佳音 席晓平 ZHAO Xiao-qiang;TANG Ping;YANG Hai-ping;WU Ya-li;TONG Jia-yin;XI Xiao-ping(The First Affiliated Hospital of Henan University of Science and Technology(Clinical Medical College of Henan University of Science and Technology),Luoyang,Henan 471000,China)

机构地区：[1]河南科技大学第一附属医院(河南科技大学临床医学院)血液内科,河南洛阳471000 [2]郑州大学第一附属医院血液内科,河南郑州450000

出　　处：《中华医院感染学杂志》2021年第13期1968-1972,共5页Chinese Journal of Nosocomiology

基　　金：河南省卫生健康委员会及河南科技大学第一附属医院共同基金资助项目(LHGJ20190546)。

摘　　要：目的探讨伏立康唑治疗多发性骨髓瘤并发侵袭性真菌感染效果与CYP2C19基因多态性的关系。方法选取2019年1月-2020年10月河南科技大学第一附属医院收治的67例多发性骨髓瘤并发侵袭性真菌感染患者为研究对象,根据基因检测代谢类型分为高代谢型16例、中间代谢型32例、低代谢型19例,采用伏立康唑治疗,比较不同代谢类型患者的疗效、不良反应、药动力学参数。结果67例患者共检出真菌菌群67株,其中白假丝酵母为20株、烟曲霉菌为18株,真菌感染部位以呼吸道最多,为44例。高、中间、低代谢型患者伏立康唑治疗有效率分别为75.00%、93.75%、100.00%,不良反应率分别为6.25%、21.88%、47.37%,差异均有统计学意义(P<0.05)。高、中间、低代谢型患者伏立康唑每千克体质量给药剂量比较,无统计学差异。伏立康唑中位标准化血药浓度由高到低依次为:低代谢型、中间代谢型、高代谢型,差异有统计学意义(P<0.05)。结论多发性骨髓瘤并发侵袭性真菌感染患者应用伏立康唑治疗的效果与CYP2C19基因多态性密切相关,CYP2C19基因型决定代谢类型,可能影响伏立康唑的血药浓度、疗效、不良反应,根据患者CYP2C19基因型可指导临床伏立康唑给药剂量。OBJECTIVE To explore the effect of voriconazole on treatment of multiple myeloma patients complicated with invasive fungal infection and its association with polymorphism of CYP2 C19 gene.METHODS Totally 67 multiple myeloma patients complicated with invasive fungal infection who were treated in the First Affiliated Hospital of Henan University of Science and Technology from Jan 2019 to Oct 2020 were recruited as the study objects and were divided into the high metabolism group with 16 cases,the intermediate metabolism group with 32 cases and the low metabolism group with 19 cases.The patients were treated with voriconazole,the therapeutic effect,adverse reactions and pharmacokinetic parameters were observed and compared among the three groups of patients.RESULTS A total of 67 strains of fungi were isolated from 67 patients,20 of which were Candida albicans,and 18 were Aspergillus fumigatus.The patients with respiratory tract infection(44 cases)were dominant among the patients with fungal infection.The effective rate of treatment with voriconazole was 75.00%in the high metabolism group,93.75%in the intermediate metabolism group,100.00%in the low metabolism group;the incidence of adverse reactions was 6.25%in the high metabolism group,21.88%in the intermediate metabolism group,47.37%in the low metabolism group;there were significant differences(P<0.05).There was no significant difference in the voriconazole dose per kilogram of body weight among the three groups.The median standardized blood concentration of voriconazole,from high to low,were as follows:the metabolism,the intermediate metabolism,the high metabolism,and there was significant difference(P<0.05).CONCLUSION The effect of voriconazole is closely associated with the polymorphism of CYP2 C19 gene of the multiple myeloma patients complicated with invasive fungal infection,the genotypes of CYP2 C19 determine the types of metabolism,which may affect the blood concentration of voriconazole,curative effect and adverse reactions.The dosage of voriconazole can b

关 键 词：多发性骨髓瘤 侵袭性真菌感染 CYP2C19基因多态性 伏立康唑 疗效 

分 类 号：R733.3[医药卫生—肿瘤]