本文選題：伏立康唑 + 棘白菌素類藥物�。� 參考：《天津醫(yī)科大學》2017年碩士論文

【摘要】：目的:1比較惡性血液病伴侵襲性真菌感染(invasive fungal infection,IFI)患者應用伏立康唑、卡泊芬凈和米卡芬凈的抗感染療效,并研究療效的影響因素。2模擬評價伏立康唑不同給藥方案在免疫抑制兒童、青少年及成人患者中對6種念珠菌和6種曲霉菌的抗感染療效。3模擬評價棘白菌素類藥物不同給藥方案在兒童IFI患者中對3種念珠菌的抗感染療效。方法:1惡性血液病伴IFI患者應用伏立康唑、卡泊芬凈和米卡芬凈的療效對比及影響因素分析對2015年1月至2016年4月入住天津市第一中心醫(yī)院血液科中確診、臨床診斷、擬診為IFI和需進行抗真菌治療但未確定IFI的住院患者,于抗真菌治療前測定K+、Na+、ALP、TP、Alb、TBil、ALT、AST、Urea、Cr、WBC、RBC、PLT、中性粒細胞、CRP、G試驗等指標。根據(jù)臨床、影像學和微生物等標準綜合評價并比較抗真菌藥物的療效,并對療效進行單因素及多因素Logistic回歸分析。2伏立康唑在免疫抑制兒童、青少年及成人患者中對念珠菌和曲霉菌的抗感染給藥方案模擬結(jié)合伏立康唑藥動學(pharmacokinetics,PK)參數(shù)和藥效學(pharmacodynamic,PD)數(shù)據(jù),及藥動/藥效學(pharmacokinetics/pharmacodynamic,PK/PD)靶值,應用蒙特卡洛方法,模擬不同給藥方案在三類人群中對6種念珠菌以及6種曲霉菌的累積反應分數(shù)(cumulative fraction of response,CFR)值。3棘白菌素類藥物在兒童IFI患者中對念珠菌的抗感染給藥方案的模擬結(jié)合棘白菌素類藥物的PK參數(shù)和PD數(shù)據(jù),以及PK/PD靶值,應用蒙特卡洛方法,模擬不同給藥方案在兒童IFI患者中對念珠菌的CFR值。結(jié)果:1惡性血液病伴IFI患者應用伏立康唑、卡泊芬凈和米卡芬凈的療效對比及影響因素分析結(jié)果伏立康唑、卡泊芬凈和米卡芬凈對惡性血液病患者伴IFI患者的抗感染治療有效率分別為66.67%、60%和65%,三組無統(tǒng)計學差異。中性粒細胞缺乏持續(xù)天數(shù)和用藥天數(shù)是影響抗感染療效的因素。2伏立康唑在兒童、青少年及成人中抗念珠菌和曲霉菌的CFR值伏立康唑所有給藥方案在三類人群中對白色念珠菌、近平滑念珠菌、擬平滑念珠菌的CFR值均≥90%。在免疫抑制兒童(2-12歲)和青少年(12-14歲,體重50 kg)患者中,當治療由熱帶念珠菌、煙曲霉菌、構(gòu)巢曲霉菌引起的感染時,僅8 mg/kg i.v.q12 h能達到CFR≥90%。在免疫抑制青少年(12-17歲)患者中,對熱帶念珠菌感染,伏立康唑4 mg/kg i.v.q12h和300 mg/kg p.o.q12h的CFR值均≥90%;對煙曲霉感染,伏立康唑4 mg/kg i.v.q12h的CFR值≥90%。在成人患者中,對念珠菌和曲霉菌(除雜色曲霉菌)感染,伏立康唑4 mg/kg i.v.q12 h和300 mg p.o.q12h的CFR值均≥90%。但對黑曲霉菌,所有給藥方案在免疫抑制兒童和青少年患者中的CFR值均≤90%;對雜色曲霉菌,所有給藥方案在三類人群中的CFR值均≤90%。3棘白菌素類藥物在兒童患者中治療念珠菌感染的CFR值卡泊芬凈不同給藥方案在兒童患者中對白色念珠菌和光滑念珠菌的CFR值均≥90%。米卡芬凈治療光滑念珠菌感染時,抑菌靶值下1 mg/kg(首劑)和0.5mg/kg qd,殺菌靶值下1.5 mg/kg(首劑)和1.5 mg/kg qd的CFR值均≥90%;對白色念珠菌,在抑菌靶值下需給予較大劑量(3.0 mg/kg)才能達到CFR值≥90%。阿尼芬凈不同給藥方案對于不同念珠菌的CFR值均≤90%。三種棘白菌素類藥物給藥方案對近平滑念珠菌的CFR值均較低。結(jié)論:1本研究中伏立康唑、卡泊芬凈和米卡芬凈對惡性血液病患者治療IFI療效相當。中性粒細胞缺乏持續(xù)天數(shù)和用藥天數(shù)是最終影響這三種抗真菌藥物療效的因素。中性粒細胞缺乏天數(shù)越短,用藥時間越長,抗真菌藥物的療效越佳。2伏立康唑常規(guī)給藥方案在免疫抑制兒童、青少年及成人中對白色念珠菌、近平滑念珠菌和擬平滑念珠菌感染均有效。在兒童和青少年患者中,對煙曲霉和構(gòu)巢曲霉感染,需應用較高劑量以達到理想的抗感染治療效果;對黑曲霉,所有給藥方案均無效;在成人中,對念珠菌和曲霉菌(除雜色曲霉菌)感染,伏立康唑4 mg/kg i.v.q12h和300 mg p.o.q12h給藥方案療效較好。對于雜色曲霉菌,所有伏立康唑給藥方案對所有患者均無效。3卡泊芬凈常規(guī)給藥方案(50 mg/m2)和高劑量米卡芬凈給藥方案在兒童患者中對白色念珠菌和光滑念珠菌感染具有較好的治療效果;阿尼芬凈多種給藥方案對念珠菌感染療效均較差。對近平滑念珠菌,所有棘白菌素類藥物不同給藥方案均無效。
[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.
【學位授予單位】：天津醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R519

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