伊曲康唑治疗恶性血液病患者侵袭性真菌感染

目的分析伊曲康唑治疗恶性血液病患者侵袭性真菌感染(IFI)的疗效和安全性。方法选择四川省人民医院血液科2006-02/2009-06住院的72例恶性血液病并发IFI患者,其中,男46例、女26例,中位年龄42岁。确诊或拟诊真菌感染或经验性治疗者使用伊曲康唑,剂量为:每次200mg,静脉滴注,1次/12h;用2d后,每次200mg,1次/d,完成疗程7d以上评价疗效。完成者共53例,疗程为732d,中位数14d。结果 53例完成疗程患者中:痊愈15例,显效19例,进步5例,无效14例,有效率为64.15%(34/53);不良反应发生率19.44%(14/72),主要表现为心血管系统、消化系统、皮肤的症状,均为一过性。结论伊曲康唑治疗恶性血液病患者IFI具有广谱抗真菌功效,其引发的不良事件较少,安全性高。     

伊曲康唑治疗血液病患者侵袭性真菌感染的疗效及影响因素分析

目的 分析伊曲康唑在治疗血液病患者合并侵袭性真菌感染(IFI)中的作用及其影响因素.方法 回顾性分析2005-2008年在天津医科大学总医院住院并接受伊曲康唑治疗的IFI患者156例,了解其疗效、影响因素及副作用等.结果 156例IFI患者中92例原发病为恶性血液病,64例为非恶性血液病;IFI拟诊77例,临床诊断79例.伊曲康唑治疗有效94例(63.5%),无效更换为其他药物54例(36.5%).恶性血液病、接受过化疗、中性粒细胞绝对值<0.5×109/L、真菌培养阳性、合并细菌感染患者伊曲康唑有效率低.年龄、体温、既往应用抗生素、G试验结果、感染部位、血红蛋白水平、血小板水平与伊曲康唑治疗疗效无关.5例患者出现药物副作用而停药,包括胃肠道不适3例和心动过速2例.结论 伊曲康唑能够高效、安全地治疗血液病患者合并IFI.原发恶性病、粒细胞缺乏、合并细菌感染、迟用药物会影响伊曲康唑抗真菌的疗效.     

伊曲康唑治疗恶性血液病合并侵袭性真菌感染127例临床分析

目的 研究伊曲康唑治疗恶性血液病合并侵袭性真菌感染的疗效.方法 回顾性分析2005年1月至2007年3月南方医科大学南方医院血液科127例恶性血液病合并侵袭性真菌感染患者应用伊曲康唑治疗的疗效.结果 伊曲康唑临床总有效率47.2%(60/127).在确诊、临床诊断和拟诊组病例的有效率分别为66.7%(16/24)、51.6%(33/64)、28.2%(11/39),拟诊组明显低于确诊和临床诊断组(P＜0.01).副反应轻微.伊曲康唑对检出茵株,接受移植、使用免疫抑制剂及负荷量给药的患者有效率明显高于对照组(P＜0.05和P＜0.01).结论 伊曲康唑治疗恶性血液病合并侵袭性真茵感染有良好的疗效,且安全可靠.     

恶性血液病合并侵袭性真菌感染73例治疗分析

目的探讨恶性血液病患者合并侵袭性真菌感染(IFI)应用氟康唑、伊曲康唑和两性霉素B治疗的结果及其影响因素。方法选择南方医科大学附属南方医院1992-01~2004-10收治的恶性血液病合并IFI患者73例,单用常规剂量的氟康唑33例、伊曲康唑26例、两性霉素B14例;氟康唑治疗无效者改用伊曲康唑9例和两性霉素B6例,伊曲康唑治疗无效改用两性霉素B和脂质体两性霉素B16例,47例同时应用了粒细胞集落细胞刺激因子(G-CSF)治疗至白细胞正常,37例联合静脉注射丙种球蛋白。结果73例IFI总的治愈率和有效率分别为53·4%和63·0%,在各诊断组间差异无显著性意义(P>0·05)。单用氟康唑治疗组的有效率显著低于伊曲康唑和两性霉素B治疗组,分别为39·4%、53·9%和57·1%(P<0·05);用氟康唑治疗无效改用伊曲康唑或两性霉素B治疗的有效率分别为77·8%和83·4%。结论伊曲康唑和两性霉素B治疗IFI的疗效相似,明显高于氟康唑;两性霉素B的副反应多。抗真菌的有效率在确诊组、临床诊断组和拟诊组之间差异无显著性意义。     

伊曲康唑治疗白血病合并侵袭性真菌感染17例疗效分析

目的探讨伊曲康唑对白血病合并侵袭性真菌感染的疗效。方法对2004年11月至2006年11月吉林大学第一临床医学院血液科的17例白血病合并侵袭性真菌感染患者的临床资料进行回顾性分析。所有患者均于诊断前给予氟康唑预防性治疗,无明显效果后改为伊曲康唑200mg,每日2次静脉滴注,连用2d。后每日1次200mg静滴,应用2周,根据病情改为口服伊曲康唑并与使用氟康唑进行比较。结果17例患者应用氟康唑无效后改为伊曲康唑治疗,有效率为64.7%,并且有52.9%的患者在1周内即显效。结论伊曲康唑是治疗白血病合并侵袭性真菌感染的有效药物,与传统的抗真菌药物相比有更广的抗菌谱,且副反应小。     

伊曲康唑静脉注射液/口服液序贯治疗血液系统疾病患者侵袭性真菌感染

目的 观察伊曲康唑静脉注射液/口服液序贯治疗血液系统疾病患者侵袭性真菌感染(IFI)的疗效及安全性.方法 所有血液系统疾病住院患者,符合IFI的诊断标准,后者类型包括确诊IFI、临床诊断IFI、拟诊IFI.本研究为开放研究,疗程为4～6周,分静脉给药阶段和口服给药阶段.静脉给药共14d,最初2d剂量为400mg/d,分两次给药,给药间隔12h;其后12d,剂量为200ms/d,1次/d.静脉用药结束后,继续给受试者序贯伊曲康唑口服液维持治疗,推荐剂量400mg/d,分两次给药(200 mg,2次/d),共用2～4周.根据受试者的病情决定每1～2周进行疗效与安伞性评价.结果 227例入组患者治疗结束后有效率为75.33%,其巾痊愈率达47.14%;227例患者治疗后205例退热(90.3%),中位退热时间5 d(2～20 d);可评价的186例患者,真菌学清除率为69.89%.发生与药物相关的不良事件11例,无与药物相关的严重不良事件发生.结论 伊曲康唑静脉注射液/口服液序贯治疗血液系统疾病患者IFI的疗效可靠,应用安全.     

伊曲康唑注射液治疗血液系统恶性肿瘤伴发真菌感染51例临床分析

目的观察伊曲康唑注射液治疗血液系统恶性肿瘤患者伴发真菌感染的临床疗效及安全性。方法选择浙江大学医学院附属第一医院血液科2004年2月至2005年4月住院恶性血液病患者51例。男35例、女16例,中位年龄42岁。确诊或拟诊真菌感染或经验性治疗使用伊曲康唑,剂量为:每次200mg,每12h1次;用2d后,每次200mg,每天1次,完成疗程7d以上评价疗效。完成者共49例,疗程为7～32d,中位数14d。结果伊曲康唑注射液临床总有效率59.2%,真菌清除率为71.4%。副反应中没有发现用药时寒战、发热等,以及胃肠道反应。肝功能异常发生率7.8%,肾功能损害发生率2%。结论伊曲康唑注射液抗菌谱较广,其注射液在治疗深部真菌感染中为高效药物,且药物安全性良好,但在使用时尚需监测肝功能。     

伊曲康唑治疗血液病合并侵袭性真菌病9例疗效分析

目的探讨伊曲康唑对在血液病合并侵袭性真菌病(IFI)患者的疗效及不良反应。方法2005年3月至2007年3月对上海交通大学附属仁济医院血液科收治的9例血液病合并侵袭性真菌病患者予以伊曲康唑静脉及口服治疗,根据临床症状和体征、真菌镜检等判定患者的疗效及不良反应。结果经伊曲康唑辅以综合治疗有效率达89%(8/9),其中痊愈7例,显效1例;1例患者因肺部体征继续进展导致呼吸衰竭死亡。未发生不能耐受的毒副反应。结论伊曲康唑在血液病合并侵袭性真菌病患者治疗中安全有效。     

血液病并呼吸道侵袭性真菌感染的临床分析

目的：探讨血液病患者并发呼吸道侵袭性真菌感染（IFI）的临床特点和不同分层诊断的真菌感染的疗效。方法：回顾性分析了我科从2005年4月-2008年3月期间住院的血液病患者85例发生真菌感染的临床表现、肺部CT影像,以及应用氟康唑、伊曲康唑、两性霉素B脂质体对不同分层诊断的抗真菌疗效。结果：①呼吸道IFI肺部CT影像学主要特征有结节样／球状阴影和靠胸膜的楔形阴影等;②微生物检测结果念珠菌属占44．7％,霉菌占12．9％,未检出真菌占42．4％;③IFI初始治疗中伊曲康唑组有效（痊愈加好转）率（67．7％）好于氟康唑组（36．0％）,差异有统计学意义,而与两性霉素B脂质体组比较差异无统计学意义;④氟康唑初始治疗无效改用伊曲康唑或两性霉素B脂质体治疗患者16例,治疗有效率分别是66．7％和75％,而伊曲康唑无效改用两性霉素B脂质体有效率为30％,2者差异有统计学意义;⑤分层治疗中,拟诊治疗、抢先治疗与确诊治疗各组间有效率比较差异无统计学意义;⑥影响抗真菌治疗效果的因素分析中主要是与原发病是否进展的相关性有统计学意义,而与年龄、粒细胞缺乏时间、抗真菌治疗时间的相关性无统计学意义。结论：①胸部CT影像学对IFI诊断有重要价值,而痰检真菌学诊断价值不大;②伊曲康唑注射液可以优先选择用于呼吸道IFI经验性治疗。     

伊曲康唑治疗血液恶性肿瘤继发真菌感染疗效观察

目的:观察伊曲康唑防治血液系统恶性肿瘤继发真菌感染的疗效和安全性。方法:68例为血液系统恶性肿瘤患者,符合经验性治疗、拟诊或确诊病例标准。对于拟诊或确诊病例,伊曲康唑续贯治疗;经验性治疗患者伊曲康唑静脉给药。经验性治疗以患者体温正常为有效。拟诊或确诊病例以临床表现消失为有效。结果:68例中,刚入组时经验性治疗病例62例,拟诊6例,治疗中11例转为拟诊病例。疗效评估时,经验性治疗51例,有效45例(88．24％);拟诊17例,有效16例(94．12％)。3例患者输注伊曲康唑后丙氨酸氨基转移酶升高,其中2例伴有天冬氨酸转氨酶升高;但无证据与伊曲康唑相关。结论:伊曲康唑防治血液系统恶性肿瘤继发真菌感染疗效确切,安全可靠。     

A prospective randomized trial of itraconazole vs fluconazole for the prevention of fungal infections in patients with acute leukemia and hematopoietic stem cell transplant recipients

Fluconazole antifungal prophylaxis is standard care in allogeneic hematopoietic stem cell transplant (HSCT) recipients, but this drug lacks anti-Aspergillus activity, the primary cause of invasive fungal infection (IFI) in many transplantation centers. We performed a randomized trial to compare itraconazole vs fluconazole, for prevention of IFIs in patients with acute leukemia (AL) and HSCT recipients. One hundred and ninety-five patients were randomly assigned to either fluconazole or itraconazole antifungal prophylaxis, after stratification into high-risk and low-risk groups. Antifungal prophylaxis was started at the beginning of chemotherapy and continued until resolution of neutropenia, or until amphotericin B treatment was started. IFI occurred in 11 (11%) of itraconazole, and in 12 (12%) fluconazole recipients. Invasive candidiasis (IC) developed in two (2%) itraconazole and one (1%) fluconazole recipients, while invasive aspergillosis (IA) developed in nine (9%) itraconazole and 11(11%) fluconazole recipients. There was no difference in the incidence of total IFI, IC and IA between the two study arms. However, there was a nonsignificant trend towards reduced mortality among patients who developed IA while receiving itraconazole prophylaxis (3/9=33% vs 8/11=73%, P=0.095).     

伊曲康唑静脉口服序贯治疗ICU侵袭性真菌感染的疗效与安全性

目的 评价伊曲康唑静脉口服序贯治疗ICU侵袭性真菌感染的疗效与安全性.方法 采用多中心、开放试验设计,选择ICU侵袭性真菌感染患者,用伊曲康唑静脉口服序贯治疗.观察用药1、2,4、6周的临床有效率和真菌清除率.结果 159例患者纳入本研究,其中拟诊58例,临床诊断81例,确诊20例.疗效分析显示,治疗1周临床有效率为35.2%,2周后明显升至73.6%.治疗第2周,拟诊病例和临床诊断病例的临床有效率分别为72.9%和72.2%,确诊病例的临床有效率为78.9%.治疗1周真菌清除率为40.9%,2周和4周后分别为75.9%和92.9%.治疗第2周,拟诊病例和临床诊断病例的真菌清除率分别为90.0%和64.6%,确诊病例的真菌清除率为84.2%.综合疗效分析显示,治疗1周的有效率为44.1%,4周后达92.9%～100.0%.与药物有关的不良反应发生率为1.3%(2/159),未见严重不良反应.结论 伊曲康唑静脉口服序贯治疗ICU侵袭性真菌感染,可获得较好的临床疗效.     

造血干细胞移植中侵袭性真菌感染的二级预防

目的 探讨有侵袭性真菌感染(IFI)病史的患者行造血干细胞移植(HSCT)时二级预防(SAP)的有效性和安全性.方法 2005年4月-2008年7月在我院行HSCT血液病患者,采用我所常规移植方案,有IFI史的患者从预处理开始进行SAP,选用既往抗真菌有效药物,预防至危险期结束(白细胞植活、无感染证据),由于无效或不良反应提前终止为退出,所有生存患者至少随访至移植后180 d.结果 入组患者26例,移植前抗IFI疗效:10例完全反应,15例部分反应,1例疾病稳定.SAP用药如下:(1)先静脉伊曲康唑后改为序贯口服液或胶囊(12例);(2)直接用伊曲康唑口服液(8例);(3)静脉脂质体两性霉素B(3例);(4)静脉卡泊芬净(2例);(5)伏立康唑口服(1例).预防过程中6例出现可能的药物相关不良事件,2例因不良事件终止SAP.SAP用药中位时间75(10～212)d,4例在预防期间IFI复发,1例预防结束后复发,IFI复发率为19.2%(5/26),IFI复发的中位时间为移植后42(1～146)d,IFI复发患者5例中3例死亡.logistic回归分析未发现与移植后IFI复发的相关危险因素.结论 既往IFI不是异基因HSCT的绝对禁忌证,SAP能有效降低真菌感染的复发,但预防的方案和疗程尚待进一步研究.     

Epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies

Invasive fungal infection (IFI) causes morbidity and mortality among patients with hematological malignancies who receive cytotoxic chemotherapy or hematopoietic stem cell transplantation (HSCT). We evaluated the incidence and treatment outcomes of proven and probable IFI in 22 institutions between 2006 and 2008 following the recent European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) consensus criteria. We analyzed 2,821 patients with hematological malignancies, including 597 who had undergone HSCT; these included patients with acute leukemia (n = 697), myelodysplastic syndrome (n = 284), lymphoma (n = 1465), or multiple myeloma (n = 375). IFIs were diagnosed in 38 (1.3%) patients (18 proven and 20 probable), including 20 patients who underwent HSCT and 18 who received chemotherapy alone; these included patients with aspergillosis (n = 23), candidiasis (n = 6), mucormycosis (n = 6), trichosporonosis (n = 2), and geotrichosis (n = 1). The incidence of IFI was 5.4 % in allogeneic HSCT patients, 0.4 % in autologous HSCT patients, and 0.8 % in patients receiving chemotherapy alone. Eighteen patients with aspergillosis were diagnosed with probable pulmonary IFI as determined by computed tomography scan and positive galactomannan assay. Overall, antifungal targeted therapies resulted in successful outcomes in 60.0 % of patients. IFI-attributable mortality rate was higher in HSCT patients than in those receiving chemotherapy alone, but the difference was not statistically significant.     

Infliximab use in patients with severe graft-versus-host disease and other emerging risk factors of non-Candida invasive fungal infections in allogeneic hematopoietic stem cell transplant recipients: a cohort study

Acute graft-versus-host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (HSCT). It has been proposed that tumor necrosis factor alpha (TNF-alpha) blockade with infliximab may be an effective treatment for severe (grades III-IV) GVHD. We determined if infliximab use in this high-risk population was associated with an additional increased risk of non-Candida invasive fungal infections (IFIs). Records of the 2000-2001 HSCT cohort at our institution were reviewed. Fifty-three (20%) of 264 evaluable patients developed severe GVHD and 11 of these 53 (21%) received infliximab for treatment. Proven or probable IFI was documented in 10 (19%) of 53 patients with severe GVHD (incidence rate of 0.99 cases/1000 GVHD patient-days). When stratified by infliximab use, 5 of 11 infliximab recipients developed an IFI (6.78 cases/1000 GVHD patient-days), compared with 5 of 42 IFI cases among nonrecipients (0.53 cases/1000 GVHD patient-days). In a time-dependent Cox regression model among patients with severe GVHD, the adjusted IFI hazard ratio of infliximab exposure was 13.6 (P =.004; 95% CI, 2.29-80.2). We conclude that infliximab administration is associated with a significantly increased risk of non-Candida IFI in HSCT recipients with severe GVHD disease. Pre-emptive systemic antifungal therapy against molds should be considered in patients who develop severe GVHD after HSCT if infliximab is used.     

造血干细胞移植后患者侵袭性真菌感染发生及危险因素分析

目的 了解造血干细胞移植（HSCT）后患者侵袭性真菌感染（ZVI）的发病率及危险因素。方法 选择2003年6月至2004年9月于我所进行HSCT的患者148例,按照我国IFI的诊断标准及临床疗效进行回顾性分析。结果 诊断IFI的患者共52例,其中确诊者35例,拟诊者17例。其发生时间为移植后2—400d,中位时间为62d。确诊IFI在移植后3、6个月及1年的累积发病率分别为15．6％、42．5％、48．9％。根据多因素分析,早期IFI的危险因素为：Ⅲ～Ⅳ度的急性移植物抗宿主病（GVHD）、广谱抗生素的长期应用及巨细胞病毒感染;晚期IFI的危险因素为：广泛型慢性GVHD和激素的长期应用。结论 具有较多危险因素的HSCT受者更易发生IFI,而避免或减少上述危险因素是预防IFI的有效方法。     

Evaluating prophylaxis of invasive fungal infections in patients with haematologic malignancies

OBJECTIVE: Patients with hematologic malignancies are at substantial risk of developing invasive fungal infections (IFI) that are associated with substantial morbidity and mortality. This article reviews the epidemiology, risk factors, and efficacy of antifungal prophylaxis in patients with hematologic malignancies. METHODS: A PubMed search was conducted to identify relevant studies with special emphasis on meta-analyses and direct comparisons between antifungal agents. RESULTS: The epidemiology of IFI has changed substantially in recent years with Candida albicans becoming less common owing to the widespread prophylactic use of azole antifungals. Invasive aspergillosis, fusariosis, and zygomycosis have increased in frequency. This change is at least partly related to the use of broad-spectrum antifungal agents, either as prophylaxis or as empirical treatment. Other risk factors for IFI include prior fungal exposure, immunosuppression, underlying disease, graft-vs.-host disease, and organ dysfunction. Inconsistent results have been reported in studies evaluating the efficacy of antifungal prophylaxis in patients at risk of IFI. Meta-analyses found that antifungals, such as fluconazole and itraconazole, are effective in decreasing IFI and IFI-related mortality, primarily owing to yeast infections in patients with more severe immunosuppression (i.e. patients undergoing bone marrow transplantation), but do not decrease the overall mortality. The European Conference on Infections in Leukemia (ECIL) guidelines currently recommend fluconazole (AI, ie. strongly recommended, based on at least 1 well-executed, randomized trial) and itraconazole (BI, ie. generally recommended, based on at least 1 well-executed, randomized trial) in allogeneic transplant recipients. Posaconazole, a triazole antifungal, has been recently shown to decrease IFI incidence and overall mortality in some high-risk patients compared with standard azoles. Based on preliminary data, a provisional AI ECIL recommendation has been given. CONCLUSIONS: Because of the substantial morbidity and mortality associated with IFI, there is a need to accurately define patient groups at greatest risk of IFI and, when appropriate, to initiate effective antifungal prophylaxis.     

Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants

Prophylactic fluconazole prevents candidiasis; however, this drug has no activity against molds. We performed a randomized trial to determine whether prophylactic itraconazole prevents invasive mold infections (IMIs). A total of 304 patients receiving allogeneic stem cell transplants (SCT) were randomized to receive fluconazole (400 mg/d) or itraconazole (oral solution 2.5 mg/kg 3 times daily, or intravenous 200 mg daily) for 180 days after SC transplantation, or until 4 weeks after discontinuation of graft-versus-host disease (GVHD) therapy. Proven or probable invasive fungal infections (IFI) were evaluated by intent-to-treat and "on-treatment" analyses. More patients in the itraconazole arm developed hepatotoxicities, and more patients were discontinued from itraconazole because of toxicities or gastrointestinal (GI) intolerance (36% versus 16%, P <.001). Intent-to-treat analysis demonstrated no difference in the incidence of IFI during the intended study period (fluconazole 16% versus itraconazole 13%, P =.46); however, fewer patients in the itraconazole arm developed IFI on treatment (fluconazole 15% versus itraconazole 7%, P =.03). Itraconazole provided better protection against IMI (fluconazole 12% versus itraconazole 5%, P =.03), but similar protection against candidiasis (3% versus 2%, P =.69). There was no difference in overall or fungal-free survival. Itraconazole appears to prevent IMI in the subset of patients who tolerate the drug; however, toxicities and poor tolerability limit its success as prophylactic therapy.     

伊曲康唑在异基因造血干细胞移植患者真菌感染中的应用

目的观察伊曲康唑治疗异基因造血干细胞移植患者的真菌感染的疗效。方法2002年10月至2005年10月诊断真菌感染的患者75例,其中确定诊断4例,临床诊断22例,拟诊49例。全部病例均于诊断后给予伊曲康唑注射液治疗,125～200mg／次,第1、2天给予2次／d,以后1次／d,病情稳定后改为口服胶囊或口服液治疗。结果总有效率为76．0％（57／75）;确诊病例3例有效（3／4）、临床诊断病例有效率为81．8％（18／22）、拟诊病例为73．5％（36／49）。临床诊断病例和拟诊病例的疗效之间差异无统计学意义（P=0．446）。结论伊曲康唑治疗异基因造血干细胞移植患者的真菌感染是有效的。