目前缺乏前瞻性的 RCT 证实对 IA 的有效性,基于以上诸多原因,伊曲康唑很少推荐用于治疗急性 IPA,仅保留用于非严重的或弱侵袭性的曲霉菌病 [2],如变应性支气管肺曲霉菌病(ABPA)等。 两性霉素 B:2002 年 GCAS 研究是一个随机、非盲、非劣性临床研究,比较了伏立康唑与两性霉素 B 用于治疗 IA,发现伏立康唑的治疗反应更好(53% vs 32%),12 周成活率也更高(71% vs 58%),同时发现伏立康唑的耐受性更好,副作用更少[7]。
2008 年 EORTC/MSG 对侵袭性真菌病(IFD)的诊断分类进行了重新定义,将 IA 的诊断分为:确诊(proven)、临床诊断 (probable) 与拟诊(possible)三类 [8]。为此 2015 年学者对先前的 GCAS 研究数据进行再分析,发现对于确诊与临床诊断的 IA 组,伏立康唑的优势更明显:54.7% vs 29.9%[9]。
2014 年有多中心研究发现,针对确诊(proven)与临床诊断 (probable) 的 IA,伏立康唑治疗组的 12 周成活率比两性霉素 B 治疗组更高(70.2% vs 54.9%,P = 0.010)[9]。
参考文献 1. Latgé J-P, Chamilos G. Aspergillus fumigatus and Aspergillosis in 2019. Clin Microbiol Rev 2019;33:e00140-18. doi: 10.1128/CMR.00140-18.2. Patterson TF, Thompson GR, Denning DW, Fishman JA, Hadley S, Herbrecht R, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis Off Publ Infect Dis Soc Am 2016;63:e1–60. doi: 10.1093/cid/ciw326.3. Ullmann AJ, Aguado JM, Arikan-Akdagli S, Denning DW, Groll AH, Lagrou K, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect 2018;24:e1–38. doi: 10.1016/j.cmi.2018.01.002.4. Douglas AP, Smibert OC, Bajel A, Halliday CL, Lavee O, McMullan B, et al. Consensus guidelines for the diagnosis and management of invasive aspergillosis, 2021. Intern Med J 2021;51 Suppl 7:143–76. doi: 10.1111/imj.15591.5. Patel DA, Gao X, Stephens JM, Forshag MS, Tarallo M. US hospital database analysis of invasive aspergillosis in the chronic obstructive pulmonary disease non-traditional host. J Med Econ 2011;14:227–37. doi: 10.3111/13696998.2011.564246.6. Grayson ML, editor. Kucers』the use of antibiotics: a clinical review of antibacterial, antifungal, antiparasitic and antiviral drugs., Seventh edition. Boca Raton: CRC Press; 2017.7. Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann J-W, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002;347:408–15. doi: 10.1056/NEJMoa020191.8. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis Off Publ Infect Dis Soc Am 2008;46:1813–21. doi: 10.1086/588660.9. Herbrecht R, Patterson TF, Slavin MA, Marchetti O, Maertens J, Johnson EM, et al. Application of the 2008 definitions for invasive fungal diseases to the trial comparing voriconazole versus amphotericin B for therapy of invasive aspergillosis: a collaborative study of the Mycoses Study Group (MSG 05) and the European Organization for Research and Treatment of Cancer Infectious Diseases Group. Clin Infect Dis Off Publ Infect Dis Soc Am 2015;60:713–20. doi: 10.1093/cid/ciu911.10. Ledoux M-P, Guffroy B, Nivoix Y, Simand C, Herbrecht R. Invasive Pulmonary Aspergillosis. Semin Respir Crit Care Med 2020;41:80–98. doi: 10.1055/s-0039-3401990.