曲霉菌感染分类及治疗药物进展
摘要
曲霉菌感染可累及多器官系统,免疫系统受损严重则可能引发侵袭性曲霉病。本文通过查阅近年来国内外的相关研究和文献资料,对曲霉菌感染的分类以及目前临床广泛使用的多烯类、三唑类、棘白菌素类三类治疗药物治疗机理及各代表药物进行归纳和汇总,并结合2016年美国感染病学会(IDSA)曲霉菌治疗指南以及近年来已发表的临床研究报道对各药物的治疗特点和不良反应进行简要概述。
引文
1 Zilberberg M D,Nathanson B H,Harrington R,et al. Epidemiology and outcomes of hospitalizations with invasive aspergillosis in the united states,2009-2013[J]. Clin Infect Dis,2018,67(5):727-735
2 何礼贤.欧洲《慢性肺曲霉病:理论基础和临床诊治指南》解读[J].中国实用内科杂志,2016,36(6):458-460
3 M Michallet,T Bénet,M Sobh,et al. Invasive aspergillosis:an important risk factor on the short-and long-term survival of acute myeloid leukemia(AML)patients[J]. Eur J Clin Microbiol Infect Dis,2012,31(6):991-997
4 罗霞. 56例肺曲霉病危险因素及临床特征分析[J].临床肺科杂志,2016,21(12):2280-2282
5 毛文炜,顾海挺,邵海燕,等.慢性阻塞性肺病急性加重期患者合并侵袭性肺曲霉菌感染的危险因素分析与临床特征[J].中华医院感染学杂志,2017,27(15):132-135
6 杜俊凤,邝相如,迟玉敏,等.两性霉素B治疗COPD合并侵袭性肺曲霉菌病的相关性研究[J].临床肺科杂志,2014,19(12):2213-2215
7 张令春,王姣峰,祁献芳,等.两性霉素B治疗侵袭性曲霉菌致肝损伤及影响因素分析[J].中国现代药物应用,2016,10(17):227-228
8 Slavin M A,Szer J,Grigg A P,et al. Guidelines for the use of antifungal agents in the treatment of invasive Candida and mould infections[J]. Intern Med J,2004,(34):192-200
9 吴武华,谷守娜,缪子敬.两性霉素B制剂的研究进展[J].天津药学,2014,26(4):70-72
10 Girois S B,Chapuis F,Decullier E,et al. Adverse effects of antifungal therapies in invasive fungal infections:review and meta-analysis[J].Eur J Clin Microbiol Infect Dis,2006,25(2):138-149
11 Bowden R,Chandrasekar P,White M H,et al. A double-blind,randomized,controlled trial of amphotericin B colloidal dispersion versus amphotericin B for treatment of invasive aspergillosis in immunocompromised patients[J]. Clin Infect Dis,2002,35(4):359-366
12 张静,徐敬根.两性霉素B与两性霉素B脂质体治疗真菌感染的疗效比较[J].当代医学,2011,17(9):102-103
13 庾胜,张碧波.两性霉素B脂质体与伏立康唑治疗侵袭性肺曲霉菌病临床对比观察[J].山东医药,2016,56(4):86-88
14 王春晖,叶晓芬,吕迁洲.两性霉素B脂质体治疗肺真菌病的疗效及安全性[J].上海医药,2016,37(1):39-42
15 Hong J Y,Kim J K,Song Y K,et al. A new self emulsifying formulation of itraconazole with improved dissolution and oral absorption[J]. J Control Release,2006,110(2):332-338
16 宋笑丹,唐景玲,邸哲婷,等.伊曲康唑自乳化释药系统的制备及溶出度研究[J].中国药学杂志,2009,44(11):846-848
17 程哲,宋永娜,王静,等.伊曲康唑治疗器官移植继发肺部曲霉菌感染12例临床观察[J].中国实用内科杂志,2010,30(10):957-958
18 蔡闯.难治性侵袭性肺曲霉菌病的补救治疗———1例报道并文献复习[D].北京:中国药理学会临床药理专业委员会、北京大学临床药理研究所,2010:283-290
19 刘璠,朱然,孔德磊,等.伊曲康唑联合糖皮质激素治疗变态反应性支气管肺曲霉菌病的疗效分析[J].中国医师进修杂志,2014,37(4):6-9
20 王鹏羽.伊曲康唑治疗变态反应性支气管肺曲霉菌病疗效的Meta分析[D].石家庄:河北医科大学,2009:2-7
21 Blanch-Wark P A,Hensley M J,Saltos N,et al. Anti-inflammatory effect of itraconazole instable allergic bronchopulmonary aspergillosis:a randomized controlled trial[J]. J Allergy Clin Immunol,2003,111(5):952-957
22 Stevens D A,Schwartz H J,Lee J Y,et al. A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis[J]. N Engl J Med,2000,342(11):756-762
23 Rüping M J,Vehreschild J J,Cornely O A. Patients at high risk of invasive fungal infections:when and how to treat[J]. Drugs,2008,68(14):1941-1962
24 赵金涛,方志鸿,王思力,等.伏立康唑胶囊预防初诊急性髓系白血病患者侵袭性曲霉菌感染的临床研究[J].中国临床药理学杂志,2016,32(22):2108-2110
25 刘明伟,张卫珍,秦兰芳,等.伏立康唑治疗变态反应性支气管肺曲菌病效果分析[J].中国老年学杂志,2016,36(10):2513-2515
26 潘小东,孙来芳,胡雪珍,等.伏立康唑治疗重症侵袭性肺曲霉菌感染的临床分析[J].中华医院感染学杂志,2015,25(22):5160-5162
27 王童,李彩霞,顾彩虹,等.伏立康唑血药浓度监测的临床应用[J].中国医院药学杂志,2017,37(21):2151-2154
28 王陶陶,陈思颖,尤海生,等.侵袭性真菌感染患者伏立康唑肝毒性的研究[J].中国药学杂志,2018,53(4):290-294
29 梁峰华,孟冬梅,谢慧,等. CYP2C19基因多态性对侵袭性真菌感染重症患者伏立康唑血药浓度的影响[J].中国医院药学杂志,2015,35(16):1456-1461
30 李宇.基于CYP2C19基因多态性检测与血药浓度监测的伏立康唑临床个体化用药研究[D].合肥:安徽中医药大学,2017:3-5
31 Morris M I. Posaconazole:a new oral antifungal agent with an expanded spectrum of activity[J]. Am Health Syst Pharm,2009,66(3):225-236
32 Rogers T R,Slavin M A,Donnelly J P. Antifungal prophylaxis during treatment for haematological malignancies:are we there yet[J]. Br J Haematol,2011,153(6):681-697
33 张明,冯春来,周军,等.耐伊曲康唑烟曲霉菌对泊沙康唑的敏感性分析[J].中华医院感染学杂志,2016,(11):2468-2469
34 Warn Peter A,Sharp Andrew,Denning David W. In vitro activity of a new triazole BAL4815,the active component of BAL8557(the watersoluble prodrug),against Aspergillus spp[J]. J Antimicrob Chemother,2006,57(1):135-138
35 Maertens J A,Raad I I,Marr K A,et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi(SECURE):a phase 3,randomisedcontrolled,non-inferiority trial[J]. Lancet,2016,387(10020):760-769
36 Cappelletty D,Eiselstein-Mc Kitrick K. The echinocandins[J]. Pharmacotherapy,2007,27(3):369-388
37 Kohno S,Izumikawa K,Ogawa K,et al. Intravenous micafungin versus voriconazole for chronic pulmonary aspergillosis:a multicenter trial in Japan[J]. J Infect,2010,61(5):410-418
38 Martin-Vicente A,Capilla J,Guarro J. Synergistic effect of anidulafungin combined with posaconazole in experimental aspergillosis[J]. Med Mycol,2017,55(4):457-460
39 Candoni A,Mestroni R,Damiani D,et al. Caspofungin as first-line therapy of pulmonary invasive fungal infections in 32 immunocompromised patients with hematologic malignancies[J]. Eur J Haematol,2005,75(3):227-233
40 Groetzner J,Kaczmarek I,Wittwer T,et al. Caspofungin as first-line therapy for the treatment of invasive aspergillosis after thoracic organ transplantation[J]. J Heart Lung Transplant,2008,27(1):1-6
41 Viscoli C,Herbrecht R,Akan H,et al. An EORTC Phase II study of caspofungin as first-line therapy of invasive aspergillosis in haematological patients[J]. J Antimicrob Chemother,2009,64(6),1274-1281
42 Herbrecht R,Maertens J,Baila L,et al. Caspofungin first-line therapy for invasive aspergillosis in allogeneic hematopoietic stem cell transplant patients:an European Organisation for Research and Treatment of Cancer study[J]. Bone Marrow Transplant,2010,45(7):1227-1233
43 Cornely O A,Vehreschild J J,Vehreschild M J,et al. Phase II dose escalation study of caspofungin for invasive aspergillosis[J]. Antimicrob Agents Chemother,2011,55(12):5798-5803
44 Maertens J,Glasmacher A,Herbrecht R,et al. Multicenter,noncomparative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis[J]. Cancer,2006,107(12):2888-2897
45 韦元元,顾红燕,陈文颖. 1例侵袭性肺曲霉菌病治疗方案分析[J].中南药学,2018,16(2):268-270
46 罗劲,陈一强,孔晋亮,等.下呼吸道烟曲霉菌分离株耐药性及基因型观察[J].山东医药,2015,55(6):14-17
47 Enoch D A,Idris S F,Aliyu S H,et al. Micafungin for the treatment of invasive aspergillosis[J]. Infect,2014,68(6):507-526
48 王志清,朱文,张艳,等.米卡芬净诱发溶血二例[J].中华临床医师杂志(电子版),2013,7(13):6211-6212
49 林天来,蔡晓祯,丁志荣,等.米卡芬净致急性溶血反应并肾衰竭[J].药物不良反应杂志,2014,16(5):309-310
50 Siopi M,Siafakas N,Vourli S,et al. Dose optimization of voriconazole/anidulafungin combination against Aspergillus fumigatus using an in vitro pharmacokinetic/pharmacodynamic model and response surface analysis:clinical implications for azole-resistant aspergillosis[J]. J Antimicrob Chemother,2016,71(11):3135-3147
2 何礼贤.欧洲《慢性肺曲霉病:理论基础和临床诊治指南》解读[J].中国实用内科杂志,2016,36(6):458-460
3 M Michallet,T Bénet,M Sobh,et al. Invasive aspergillosis:an important risk factor on the short-and long-term survival of acute myeloid leukemia(AML)patients[J]. Eur J Clin Microbiol Infect Dis,2012,31(6):991-997
4 罗霞. 56例肺曲霉病危险因素及临床特征分析[J].临床肺科杂志,2016,21(12):2280-2282
5 毛文炜,顾海挺,邵海燕,等.慢性阻塞性肺病急性加重期患者合并侵袭性肺曲霉菌感染的危险因素分析与临床特征[J].中华医院感染学杂志,2017,27(15):132-135
6 杜俊凤,邝相如,迟玉敏,等.两性霉素B治疗COPD合并侵袭性肺曲霉菌病的相关性研究[J].临床肺科杂志,2014,19(12):2213-2215
7 张令春,王姣峰,祁献芳,等.两性霉素B治疗侵袭性曲霉菌致肝损伤及影响因素分析[J].中国现代药物应用,2016,10(17):227-228
8 Slavin M A,Szer J,Grigg A P,et al. Guidelines for the use of antifungal agents in the treatment of invasive Candida and mould infections[J]. Intern Med J,2004,(34):192-200
9 吴武华,谷守娜,缪子敬.两性霉素B制剂的研究进展[J].天津药学,2014,26(4):70-72
10 Girois S B,Chapuis F,Decullier E,et al. Adverse effects of antifungal therapies in invasive fungal infections:review and meta-analysis[J].Eur J Clin Microbiol Infect Dis,2006,25(2):138-149
11 Bowden R,Chandrasekar P,White M H,et al. A double-blind,randomized,controlled trial of amphotericin B colloidal dispersion versus amphotericin B for treatment of invasive aspergillosis in immunocompromised patients[J]. Clin Infect Dis,2002,35(4):359-366
12 张静,徐敬根.两性霉素B与两性霉素B脂质体治疗真菌感染的疗效比较[J].当代医学,2011,17(9):102-103
13 庾胜,张碧波.两性霉素B脂质体与伏立康唑治疗侵袭性肺曲霉菌病临床对比观察[J].山东医药,2016,56(4):86-88
14 王春晖,叶晓芬,吕迁洲.两性霉素B脂质体治疗肺真菌病的疗效及安全性[J].上海医药,2016,37(1):39-42
15 Hong J Y,Kim J K,Song Y K,et al. A new self emulsifying formulation of itraconazole with improved dissolution and oral absorption[J]. J Control Release,2006,110(2):332-338
16 宋笑丹,唐景玲,邸哲婷,等.伊曲康唑自乳化释药系统的制备及溶出度研究[J].中国药学杂志,2009,44(11):846-848
17 程哲,宋永娜,王静,等.伊曲康唑治疗器官移植继发肺部曲霉菌感染12例临床观察[J].中国实用内科杂志,2010,30(10):957-958
18 蔡闯.难治性侵袭性肺曲霉菌病的补救治疗———1例报道并文献复习[D].北京:中国药理学会临床药理专业委员会、北京大学临床药理研究所,2010:283-290
19 刘璠,朱然,孔德磊,等.伊曲康唑联合糖皮质激素治疗变态反应性支气管肺曲霉菌病的疗效分析[J].中国医师进修杂志,2014,37(4):6-9
20 王鹏羽.伊曲康唑治疗变态反应性支气管肺曲霉菌病疗效的Meta分析[D].石家庄:河北医科大学,2009:2-7
21 Blanch-Wark P A,Hensley M J,Saltos N,et al. Anti-inflammatory effect of itraconazole instable allergic bronchopulmonary aspergillosis:a randomized controlled trial[J]. J Allergy Clin Immunol,2003,111(5):952-957
22 Stevens D A,Schwartz H J,Lee J Y,et al. A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis[J]. N Engl J Med,2000,342(11):756-762
23 Rüping M J,Vehreschild J J,Cornely O A. Patients at high risk of invasive fungal infections:when and how to treat[J]. Drugs,2008,68(14):1941-1962
24 赵金涛,方志鸿,王思力,等.伏立康唑胶囊预防初诊急性髓系白血病患者侵袭性曲霉菌感染的临床研究[J].中国临床药理学杂志,2016,32(22):2108-2110
25 刘明伟,张卫珍,秦兰芳,等.伏立康唑治疗变态反应性支气管肺曲菌病效果分析[J].中国老年学杂志,2016,36(10):2513-2515
26 潘小东,孙来芳,胡雪珍,等.伏立康唑治疗重症侵袭性肺曲霉菌感染的临床分析[J].中华医院感染学杂志,2015,25(22):5160-5162
27 王童,李彩霞,顾彩虹,等.伏立康唑血药浓度监测的临床应用[J].中国医院药学杂志,2017,37(21):2151-2154
28 王陶陶,陈思颖,尤海生,等.侵袭性真菌感染患者伏立康唑肝毒性的研究[J].中国药学杂志,2018,53(4):290-294
29 梁峰华,孟冬梅,谢慧,等. CYP2C19基因多态性对侵袭性真菌感染重症患者伏立康唑血药浓度的影响[J].中国医院药学杂志,2015,35(16):1456-1461
30 李宇.基于CYP2C19基因多态性检测与血药浓度监测的伏立康唑临床个体化用药研究[D].合肥:安徽中医药大学,2017:3-5
31 Morris M I. Posaconazole:a new oral antifungal agent with an expanded spectrum of activity[J]. Am Health Syst Pharm,2009,66(3):225-236
32 Rogers T R,Slavin M A,Donnelly J P. Antifungal prophylaxis during treatment for haematological malignancies:are we there yet[J]. Br J Haematol,2011,153(6):681-697
33 张明,冯春来,周军,等.耐伊曲康唑烟曲霉菌对泊沙康唑的敏感性分析[J].中华医院感染学杂志,2016,(11):2468-2469
34 Warn Peter A,Sharp Andrew,Denning David W. In vitro activity of a new triazole BAL4815,the active component of BAL8557(the watersoluble prodrug),against Aspergillus spp[J]. J Antimicrob Chemother,2006,57(1):135-138
35 Maertens J A,Raad I I,Marr K A,et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi(SECURE):a phase 3,randomisedcontrolled,non-inferiority trial[J]. Lancet,2016,387(10020):760-769
36 Cappelletty D,Eiselstein-Mc Kitrick K. The echinocandins[J]. Pharmacotherapy,2007,27(3):369-388
37 Kohno S,Izumikawa K,Ogawa K,et al. Intravenous micafungin versus voriconazole for chronic pulmonary aspergillosis:a multicenter trial in Japan[J]. J Infect,2010,61(5):410-418
38 Martin-Vicente A,Capilla J,Guarro J. Synergistic effect of anidulafungin combined with posaconazole in experimental aspergillosis[J]. Med Mycol,2017,55(4):457-460
39 Candoni A,Mestroni R,Damiani D,et al. Caspofungin as first-line therapy of pulmonary invasive fungal infections in 32 immunocompromised patients with hematologic malignancies[J]. Eur J Haematol,2005,75(3):227-233
40 Groetzner J,Kaczmarek I,Wittwer T,et al. Caspofungin as first-line therapy for the treatment of invasive aspergillosis after thoracic organ transplantation[J]. J Heart Lung Transplant,2008,27(1):1-6
41 Viscoli C,Herbrecht R,Akan H,et al. An EORTC Phase II study of caspofungin as first-line therapy of invasive aspergillosis in haematological patients[J]. J Antimicrob Chemother,2009,64(6),1274-1281
42 Herbrecht R,Maertens J,Baila L,et al. Caspofungin first-line therapy for invasive aspergillosis in allogeneic hematopoietic stem cell transplant patients:an European Organisation for Research and Treatment of Cancer study[J]. Bone Marrow Transplant,2010,45(7):1227-1233
43 Cornely O A,Vehreschild J J,Vehreschild M J,et al. Phase II dose escalation study of caspofungin for invasive aspergillosis[J]. Antimicrob Agents Chemother,2011,55(12):5798-5803
44 Maertens J,Glasmacher A,Herbrecht R,et al. Multicenter,noncomparative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis[J]. Cancer,2006,107(12):2888-2897
45 韦元元,顾红燕,陈文颖. 1例侵袭性肺曲霉菌病治疗方案分析[J].中南药学,2018,16(2):268-270
46 罗劲,陈一强,孔晋亮,等.下呼吸道烟曲霉菌分离株耐药性及基因型观察[J].山东医药,2015,55(6):14-17
47 Enoch D A,Idris S F,Aliyu S H,et al. Micafungin for the treatment of invasive aspergillosis[J]. Infect,2014,68(6):507-526
48 王志清,朱文,张艳,等.米卡芬净诱发溶血二例[J].中华临床医师杂志(电子版),2013,7(13):6211-6212
49 林天来,蔡晓祯,丁志荣,等.米卡芬净致急性溶血反应并肾衰竭[J].药物不良反应杂志,2014,16(5):309-310
50 Siopi M,Siafakas N,Vourli S,et al. Dose optimization of voriconazole/anidulafungin combination against Aspergillus fumigatus using an in vitro pharmacokinetic/pharmacodynamic model and response surface analysis:clinical implications for azole-resistant aspergillosis[J]. J Antimicrob Chemother,2016,71(11):3135-3147