钟新连,洪晓丹,程刚

• 1:沈阳药科大学生命科学与生物制药学院
• 2:惠州市中大惠亚医院药学部
• 3:中山大学附属第一医院药学部

摘要(Abstract)：

目的 运用Meta分析方法系统评价伏立康唑对侵袭性肺曲霉菌感染（IPA）患者的预防作用和治疗效果，分析其有效性和安全性，为IPA早期干预和临床治疗方案的决策提供循证医学证据。方法 系统全面检索各中英文数据库，收集公开发表的伏立康唑预防或治疗IPA患者的研究与报道，纳入其中设计严谨、方法 可靠的观察性研究并提取有效数据。结果 本研究共纳入23篇文献（共3,144名研究对象），Meta分析结果显示，伏立康唑对IPA的早期预防（OR=0.17, 95%CI:0.09～0.33, P<0.01）和临床治疗（OR=4.82, 95%CI:3.84～6.06, P<0.01）均显示出了明显的优势，能够降低IPA患者的全因死亡率（OR=0.34,95%CI:0.21～0.54, P<0.01）。结论 伏立康唑帮助患者避免了严重感染的风险，降低了医疗系统的负担，且预防用药减少了治疗的时间和资源，这对于患者、医疗保健提供者和社会都具有积极的影响。

关键词(KeyWords)： 伏立康唑;侵袭性肺曲霉菌感染;Meta分析;预防作用

Abstract:

Keywords:

基金项目(Foundation): 辽宁省教育厅科学技术研究项目（2020LJC12）

作者(Author): 钟新连,洪晓丹,程刚

DOI: 10.14146/j.cnki.cjp.2025.03.001

参考文献(References)：

• [1] LEDOUX M, GUFFROY B, NIVOIX Y, et al. Invasive pulmonary aspergillosis[J]. Semin Respir Crit Care Med,2020, 41(1):80-98.
• [2]高东田,刘利华,申爱华,等.侵袭性肺曲霉菌感染实验诊断新进展[J].检验医学, 2021,36(4):453-461.
• [3]张玉.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].中外医学研究, 2019,17(14):42-44.
• [4]杨羽,唐丽丽,尚静,等.慢性阻塞性肺疾病急性加重期患者发生侵袭性肺曲霉菌感染的因素[J].中国医学创新, 2022,19(24):65-69.
• [5] VANDERBEKE L, JANSSEN N A F, BERGMANS D C J J, et al. Posaconazole for prevention of invasive pulmonary aspergillosis in critically ill influenza patients(POSA-FLU):a randomised, open-label, proof-of-concept trial[J].Intensive Care Med, 2021,47(6):674-686.
• [6] SARFATI S, WILS J, LAMBERT T, et al. Therapeutic drug monitoring of sputum voriconazole in pulmonary aspergillosis[J]. Pharmaceutics, 2022,14(8):1598.
• [7] PATTERSON T F, THOMPSON G R R, DENNING D W, et al. Practice guidelines for the diagnosis and management of aspergillosis:2016 update by the infectious diseases society of America[J]. Clin Infect Dis, 2016,63(4):e1-e60.
• [8]邬兰,张永,曾宪涛. QUADAS-2在诊断准确性研究的质量评价工具中的应用[J].湖北医药学院学报,2013,32(3):201-208.
• [9]黄玉香,沈建通,刘雨今.诊断试验准确性比较研究偏倚风险评价工具QUADAS-C解读[J].中国循证医学杂志, 2022,22(9):1108-1116.
• [10]李静,李幼平.不断完善与发展的Cochrane系统评价[J].中国循证医学杂志, 2008(9):742-743.
• [11] CUMPSTON M, LI T, PAGE M J, et al. Updated guidance for trusted systematic reviews:a new edition of the cochrane handbook for systematic reviews of interventions[J]. Cochrane Database Syst Rev, 2019,10(1):142.
• [12] KIRKPATRICK W R, NAJVAR L K, VALLOR A C, et al. Prophylactic efficacy of single dose pulmonary administration of amphotericin B inhalation powder in a guinea pig model of invasive pulmonary aspergillosis[J]. J Antimicrob Chemother, 2012,67(4):970-976.
• [13]吴朝阳.伏立康唑治疗侵袭性肺曲霉菌病的临床价值[J].中国实用医药, 2010,5(15):76-77.
• [14]宫本法,林冬,魏辉,等.伏立康唑在急性髓系白血病诱导化疗期间初级预防侵袭性肺曲霉菌感染的研究[J].中国实验血液学杂志, 2018,26(5):1269-1274.
• [15]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.
• [16] MAERTENS J A, RAHAV G, Lee D, et al. Posaconazole versus voriconazole for primary treatment of invasive aspergillosis:a phase 3, randomised, controlled, non-inferiority trial[J]. Lancet(London, England), 2021,397(10273):499-509.
• [17]孟帅.伏立康唑治疗慢性阻塞性肺疾病合并侵袭性肺曲霉菌病的临床研究[J].山西医药杂志, 2020,49(3):282-284.
• [18]张恩俊,芮绍军,赵建荣,等.伏立康唑治疗肺结核合并侵袭性肺曲霉菌病的疗效观察[J].临床合理用药杂志, 2019,12(4):16-17.
• [19]丁菲,邵宁,贾树田,等.伏立康唑治疗肾移植术后侵袭性肺曲霉菌病的疗效观察[J].广西医科大学学报,2018,35(2):264-267.
• [20]霍达凯.两性霉素B脂质体与伏立康唑联合治疗肺结核合并侵袭性肺曲霉菌病的疗效观察[J].中国医药指南, 2014,12(11):55-56.
• [21]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.
• [22]刘涛,石翠翠,张晓培,等.伏立康唑治疗重型肝炎并发侵袭性肺曲霉菌病的疗效[J].江苏医药, 2013,39(5):548-550.
• [23]陈泉芳,邹小英,王威,等.两种治疗方法对肺结核合并侵袭性肺曲霉菌病的疗效观察[J].中华医院感染学杂志, 2012,22(17):3782-3784.
• [24]段旺旺,雷杰喻,白延宁,等.伏立康唑与胸腺肽a1联合治疗老年COPD合并侵袭性肺曲霉菌病的临床效果[J].贵州医药, 2021,45(11):1719-1720.
• [25]宋宁,史金英,高兰芳,等.伏立康唑对慢性阻塞性肺疾病急性加重期合并侵袭性肺曲霉菌病疗效分析[J].河北医药, 2012,34(2):240-241.
• [26]陈敏,李昌崇,周海霞,等.伏立康唑在儿童急性白血病肺曲霉菌感染二级预防中的应用[J].温州医科大学学报, 2016,46(6):454-457.
• [27] VERINGA A, BRUGGEMANN R J, SPAN L F R, et al. Therapeutic drug monitoring-guided treatment versus standard dosing of voriconazole for invasive aspergillosis in haematological patients:a multicentre, prospective,cluster randomised, crossover clinical trial[J]. Int J Antimicrob Agents, 2023,61(2):106711.
• [28] MAHMOUD E, ALZAHRANI M, LOUTFI S, et al. Comparing invasive pulmonary aspergillosis mortality between liposomal amphotericin B and voriconazole in patients with hematological malignancy or hematopoietic stem cell transplantation[J]. Cureus, 2022,14(11):e31762.
• [29] HARADA S, OHKUSHI D, NAKANO K, et al. Fatal invasive pulmonary aspergillosis caused by voriconazoleresistant Aspergillus tubingensis in a patient with solid tumor[J]. J Infect Chemother, 2020,26(3):301-304.
• [30] LESTRADE P P, BENTVELSEN R G, SCHAUWVLIEGHE A F A D, et al. Voriconazole resistance and mortality in invasive aspergillosis:A multicenter retrospective cohort study[J]. Clin Infect Dis, 2019,68(9):1463-1471.
• [31] TOLMAN J A, WIEDERHOLD N P, MCCONVILLE J T, et al. Inhaled voriconazole for prevention of invasive pulmonary aspergillosis[J]. Antimicrob Agents Chemother, 2009,53(6):2613-2615.
• [32] COSTA-PINTO R, KLINK S, ROTHERHAM H, et al. Assessing the safety profile of voriconazole use in suspected COVID-19-associated pulmonary aspergillosis-a two-centre observational study[J]. Medical mycology, 2023,61(6):2345-2367.
• [33] YOSHII N, YAMADA K, NIKI M, et al. Invasive pulmonary aspergillosis caused by aspergillus terreus diagnosed using virtual bronchoscopic navigation and endobronchial ultrasonography with guide sheath and successfully treated with liposomal amphotericin B[J]. Infection, 2021,49(5):1049-1054.
• [34] INOUE K, MURAMATSU K, NISHIMURA T, et al. Association between early diagnosis of and inpatient mortality from invasive pulmonary aspergillosis among patients without immunocompromised host factors:a nationwide observational study[J]. Int J Infect Dis, 2022,122(1):279-284.
• [35] CHAN A, DANG C, WISNIEWSKI J, et al. A cost-effectiveness analysis comparing pembrolizumab-axitinib,nivolumab-ipilimumab, and sunitinib for treatment of advanced renal cell carcinoma[J]. Am J Clin Oncol, 2022,45(2):66-73.
• [36]王凯.经纤维支气管镜肺泡灌洗两性霉素B联合伏立康唑在侵袭性肺真菌病中的应用[J].中国现代医药杂志, 2016,18(10):33-35.
• [37] ADEMI Z, LIEW D, HOLLINGSWORTH B, et al. Is it cost-effective to increase aspirin use in outpatient settings for primary or secondary prevention? Simulation data from the REACH registry[J]. Australian Cohort Cardiovasc Ther, 2013,31(1):45-52.
• [38] 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, randomised-controlled, noninferiority trial[J]. Lancet(London, England), 2016,387(10020):760-769.