抗真菌药治疗侵袭性真菌感染疗效评价及给药方案优化

发布时间：2018-06-28 14:02

本文选题：伏立康唑 + 棘白菌素类药物　；参考：《天津医科大学》2017年硕士论文

【摘要】：目的:1比较恶性血液病伴侵袭性真菌感染(invasive fungal infection,IFI)患者应用伏立康唑、卡泊芬净和米卡芬净的抗感染疗效,并研究疗效的影响因素。2模拟评价伏立康唑不同给药方案在免疫抑制儿童、青少年及成人患者中对6种念珠菌和6种曲霉菌的抗感染疗效。3模拟评价棘白菌素类药物不同给药方案在儿童IFI患者中对3种念珠菌的抗感染疗效。方法:1恶性血液病伴IFI患者应用伏立康唑、卡泊芬净和米卡芬净的疗效对比及影响因素分析对2015年1月至2016年4月入住天津市第一中心医院血液科中确诊、临床诊断、拟诊为IFI和需进行抗真菌治疗但未确定IFI的住院患者,于抗真菌治疗前测定K+、Na+、ALP、TP、Alb、TBil、ALT、AST、Urea、Cr、WBC、RBC、PLT、中性粒细胞、CRP、G试验等指标。根据临床、影像学和微生物等标准综合评价并比较抗真菌药物的疗效,并对疗效进行单因素及多因素Logistic回归分析。2伏立康唑在免疫抑制儿童、青少年及成人患者中对念珠菌和曲霉菌的抗感染给药方案模拟结合伏立康唑药动学(pharmacokinetics,PK)参数和药效学(pharmacodynamic,PD)数据,及药动/药效学(pharmacokinetics/pharmacodynamic,PK/PD)靶值,应用蒙特卡洛方法,模拟不同给药方案在三类人群中对6种念珠菌以及6种曲霉菌的累积反应分数(cumulative fraction of response,CFR)值。3棘白菌素类药物在儿童IFI患者中对念珠菌的抗感染给药方案的模拟结合棘白菌素类药物的PK参数和PD数据,以及PK/PD靶值,应用蒙特卡洛方法,模拟不同给药方案在儿童IFI患者中对念珠菌的CFR值。结果:1恶性血液病伴IFI患者应用伏立康唑、卡泊芬净和米卡芬净的疗效对比及影响因素分析结果伏立康唑、卡泊芬净和米卡芬净对恶性血液病患者伴IFI患者的抗感染治疗有效率分别为66.67%、60%和65%,三组无统计学差异。中性粒细胞缺乏持续天数和用药天数是影响抗感染疗效的因素。2伏立康唑在儿童、青少年及成人中抗念珠菌和曲霉菌的CFR值伏立康唑所有给药方案在三类人群中对白色念珠菌、近平滑念珠菌、拟平滑念珠菌的CFR值均≥90%。在免疫抑制儿童(2-12岁)和青少年(12-14岁,体重50 kg)患者中,当治疗由热带念珠菌、烟曲霉菌、构巢曲霉菌引起的感染时,仅8 mg/kg i.v.q12 h能达到CFR≥90%。在免疫抑制青少年(12-17岁)患者中,对热带念珠菌感染,伏立康唑4 mg/kg i.v.q12h和300 mg/kg p.o.q12h的CFR值均≥90%;对烟曲霉感染,伏立康唑4 mg/kg i.v.q12h的CFR值≥90%。在成人患者中,对念珠菌和曲霉菌(除杂色曲霉菌)感染,伏立康唑4 mg/kg i.v.q12 h和300 mg p.o.q12h的CFR值均≥90%。但对黑曲霉菌,所有给药方案在免疫抑制儿童和青少年患者中的CFR值均≤90%;对杂色曲霉菌,所有给药方案在三类人群中的CFR值均≤90%。3棘白菌素类药物在儿童患者中治疗念珠菌感染的CFR值卡泊芬净不同给药方案在儿童患者中对白色念珠菌和光滑念珠菌的CFR值均≥90%。米卡芬净治疗光滑念珠菌感染时,抑菌靶值下1 mg/kg(首剂)和0.5mg/kg qd,杀菌靶值下1.5 mg/kg(首剂)和1.5 mg/kg qd的CFR值均≥90%;对白色念珠菌,在抑菌靶值下需给予较大剂量(3.0 mg/kg)才能达到CFR值≥90%。阿尼芬净不同给药方案对于不同念珠菌的CFR值均≤90%。三种棘白菌素类药物给药方案对近平滑念珠菌的CFR值均较低。结论:1本研究中伏立康唑、卡泊芬净和米卡芬净对恶性血液病患者治疗IFI疗效相当。中性粒细胞缺乏持续天数和用药天数是最终影响这三种抗真菌药物疗效的因素。中性粒细胞缺乏天数越短,用药时间越长,抗真菌药物的疗效越佳。2伏立康唑常规给药方案在免疫抑制儿童、青少年及成人中对白色念珠菌、近平滑念珠菌和拟平滑念珠菌感染均有效。在儿童和青少年患者中,对烟曲霉和构巢曲霉感染,需应用较高剂量以达到理想的抗感染治疗效果;对黑曲霉,所有给药方案均无效;在成人中,对念珠菌和曲霉菌(除杂色曲霉菌)感染,伏立康唑4 mg/kg i.v.q12h和300 mg p.o.q12h给药方案疗效较好。对于杂色曲霉菌,所有伏立康唑给药方案对所有患者均无效。3卡泊芬净常规给药方案(50 mg/m2)和高剂量米卡芬净给药方案在儿童患者中对白色念珠菌和光滑念珠菌感染具有较好的治疗效果;阿尼芬净多种给药方案对念珠菌感染疗效均较差。对近平滑念珠菌,所有棘白菌素类药物不同给药方案均无效。
[Abstract]:Objective: 1 to compare the effects of voriconazole, Carbo Finn Jing and Mika Finn Jing on the efficacy of voriconazole, Carbo Finn Jing and Mika Finn Jing in patients with malignant hematopathy and invasive fungal infection (IFI infection, IFI), and to study the influencing factors of the curative effect.2 simulation of the different regimens of voriconazole in immunosuppressive, adolescent and adult patients with 6 species of Candida and 6 The anti infection effect of Aspergillus species.3 simulated the anti infection effect of 3 kinds of Candida albicans in children's IFI patients. Methods: 1 malignant hematological diseases with IFI patients with voriconazole, caspofungin and Mika Finn Jing and the influence factors analysis from January 2015 to April 2016 in Tianjin City In the Department of Hematology, the first center hospital, the diagnosis, the clinical diagnosis, the IFI and the antifungal treatment, but the inpatient of the unconfirmed IFI, were measured before antifungal treatment of K+, Na+, ALP, TP, Alb, TBil, ALT, AST, Urea, Cr, polymorphonuclear cells, etc. according to the clinical, imaging and microbial standards. The efficacy of antifungal agents and a single factor and multiple factor Logistic regression analysis of the efficacy of.2 voriconazole in immunosuppressed children, adolescent and adult patients with Candida and Aspergillus infection regimens combined with volantio pharmacokinetics (pharmacokinetics, PK) parameters and pharmacodynamics (pharmacodynamic, PD) data, and Pharmacokinetics/pharmacodynamic (PK/PD) target value, Monte Carlo method was used to simulate the cumulative response fraction of 6 Candida albicans and 6 Aspergillus species (cumulative fraction of response, CFR) of different drug delivery schemes in three groups of population. The anti infection of acanthomycin to Candida albicans in children's IFI The simulation of the drug regimen combined with the PK parameters and PD data of echinocinomycin, and the target value of PK/PD, and used the Monte Carlo method to simulate the CFR values of Candida albicans in children with IFI. Results: 1 the effects of voriconazole, caspofungin and Mika Finn Jing on the treatment of IFI patients with IFI and the analysis of influencing factors Kahide Tachiyasu, caspofungin and Mika Finn Jing had 66.67%, 60% and 65% effective rates of anti infection treatment in patients with malignant hematopathy with IFI, and there was no statistical difference in the three groups. The lack of duration of neutrophils and the number of days of drug use were the factors affecting the anti infection effect,.2 resistant Candida in children, adolescents and adults. The CFR value of Aspergillus fumigate in all the regimens of Candida albicans, Candida albicans, and Candida albicans in three groups of people were more than 90%. in the immunosuppressed children (2-12 years old) and adolescents (12-14 years old, 50 kg), when the treatment was caused by Candida tropicalis, Aspergillus fumigatus, and Aspergillus niger, only 8 mg/k G i.v.q12 h can reach CFR > 90%. in immunosuppressed adolescents (12-17 years old), the value of CFR values for Candida tropicalis infection, volconazole 4 mg/kg i.v.q12h and 300 mg/kg p.o.q12h, and the infection of Aspergillus fumigatus and 4 mg/kg i.v.q12h of voriconazole in adult patients, Candida and Aspergillus (Aspergillus niger) infection The CFR values of voriconazole 4 mg/kg i.v.q12 h and 300 mg p.o.q12h were equal to 90%., but for Aspergillus niger, the CFR value of all the regimens in immunosuppressed and adolescent patients was less than 90%; for Aspergillus niger, the CFR values of all regimens in the three groups were less than 90%.3 echinosin in the treatment of candidal feeling in children. The CFR value of the CFR value of caspofungin in children with Candida albicans and Candida albicans was more than 90%. Mika Finn Jing in the treatment of Candida smooth Candida infection, 1 mg/kg (first agent) and 0.5mg/kg QD under the bacteriostasis target value, and the CFR values of 1.5 mg/kg (first agent) and 1.5 mg/kg QD under the target value of bactericidal target were equal to 90%, and the Bacteriostasis of Candida albicans was in bacteriostasis. The target value should be given a large dose (3 mg/kg) to reach the CFR value more than 90%. aliffins and the different CFR values for different Candida albicans are less than 90%. and three kinds of echinocinomycin are low in the CFR value of the Candida albicans. Conclusion: in the 1 study, voriconazole, Carbo Finn Jing and Mika Finn Jing were in the patients with malignant hematopathy. The lack of duration of neutrophils and the number of days of drug use are the factors that ultimately affect the efficacy of these three antifungal agents. The shorter the number of neutrophils, the longer the drug use, the better the antifungal drug is, the better the.2 voriconazole routine regimen is on the white beads in the immunosuppressed children, adolescents and adults. Bacteria, Candida albicans and Candida albicans are all effective. In children and adolescents, a high dose of Aspergillus fumigatus and Aspergillus nests should be used to achieve the desired effect of anti infection. All the regimens of Aspergillus Niger are ineffective; in adults, Candida and Aspergillus (Aspergillus niger) infection, Fu Likang The efficacy of azole 4 mg/kg i.v.q12h and 300 mg p.o.q12h was better. For Aspergillus Aspergillus, all the volcconazole regimens were not effective for all patients with.3 caspofunnet routine administration (50 mg/m2) and high dose of miliaven net administration scheme in children with Candida albicans and Candida smooth infection The effect of different regimens of iffinqing on Candida infection was poor.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R519

【参考文献】