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.     

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。     

151例侵袭性真菌感染的临床特点分析

目的探讨侵袭性真菌感染（IFI）的临床特点,高危感染因素及对不同药物的治疗反应。方法采取回顾性研究探讨151例确诊为侵袭性真菌感染患者的临床特点,高危易感因素,病原学分布情况及其对不同药物治疗的反应。评估不同药物治疗IFI的临床疗效和不良反应。对相应结果应用SPSS11．0软件包进行统计分析。结果151例IFI患者中感染前使用广谱抗生素者占49．02％,粒细胞缺乏者占45．10％。感染部位以单纯呼吸道感染为主（74．17％）。确诊和临床诊断的43例患者中共分离出致病真菌43例,其中自假丝酵母菌所占比例最大（占44．19％）。伏立康唑组的总有效率与两性霉素B组比较无显著性差异（P〉0．05）,但其不良反应发生率低于两性霉素B组（11．62％比63．08％,P〈0．05）。结论本组侵袭性真菌感染以念珠菌属感染为主,广谱抗生素的应用及粒细胞缺乏是侵袭性真菌感染的高危易感因素。伏立康唑的临床疗效与两性霉素B相当,但不良反应的发生率较两性霉素B少。     

伊曲康唑针剂治疗恶性血液病化疗后深部真菌感染疗效观察

恶性血液病患者因化疗、大剂量糖皮质激素及免疫抑制剂的使用，临床上常出现无明显感染灶的高热，且经广谱抗生素治疗无效，此时因考虑深部真菌感染的可能。日前抗真菌药物主要为咪唑类如氟康唑、伊曲康唑和多烯类如两性霉素B（AMB）。因AMB副作用大，疗程长，临床七使用受到一定限制。我院采用伊曲康唑针剂治疗恶性血液病患者化疗后长期高热的确诊或疑似深部真菌感染者22例，取得较好的疗效。     

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。     

伊曲康唑治疗恶性血液病伴肾功能不全患者侵袭性真菌感染的疗效观察

恶性血液病患者侵袭性真菌感染(IFI)的发生率日益增高,成为危及患者生命的重要危险因素.目前,伊曲康唑在IFI的治疗中得到广泛应用,已成为部分类型IFI感染的一线选择[1].但是,对伴有肾功能不全的:IFI患者,伊曲康唑能否应用?是否安全?目前国内外很少报道.我们对15例恶性血液病伴有肾功能不全患者IFI应用伊曲康唑的疗效及安全性进行了临床分析.     

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。     

利奈唑胺治疗中性粒细胞减少血液病革兰阳性球菌感染76例临床分析

目的分析利奈唑胺治疗中性粒细胞减少血液病患者革兰阳性(G+)球菌感染的疗效和安全性。方法收集2008年8月至2009年5月苏州大学附属第一医院血液科收治的76例中性粒细胞减少疑诊G+球菌感染血液病患者,以利奈唑胺600 mg,每日2次抗感染治疗,从临床表现和病原学方面评价其疗效,同时观察药物不良反应。结果 76例患者总有效率为91.26%。单用利奈唑胺组有效率92.31%;混合感染初始即联合利奈唑胺组有效率92.59%;混合感染初始联合其他抗G+菌药物后换用利奈唑胺组有效率88.89%。3组病例体温控制中位时间分别为3.313、.76及6.58 d。恶性血液病不缓解、长期使用广谱抗生素及合并G-菌感染是影响利奈唑胺疗效的3个重要因素。利奈唑胺不良反应发生率为26.31%,发生肝功能轻度异常患者未予停用利奈唑胺,经保肝治疗后肝功迅速恢复,其余患者均予以停药后3 d至2周后患者。结论利奈唑胺治疗粒细胞减少血液病患者G+菌感染具有明显疗效。轻症感染或病原学检查提示明确G+菌感染病例,针对性单药利奈唑胺即可取得明显疗效。重症混合感染首选联合利奈唑胺者疗效优于利奈唑胺作为二线药物者。恶性血液病完全缓解、避免广谱抗生素长期使用和及时有效病原体检查有助于利奈唑胺发挥抗G+菌感染的疗效。利奈唑胺引发的不良反应较少。     

两性霉素B治疗COPD合并侵袭性肺曲霉菌病的相关性研究

目的对比两性霉素B与伊曲康唑治疗C0PD合并侵袭性肺曲霉菌病(IPA)的临床疗效、不良反应及治疗费用。方法对比研究我院两性霉素B治疗COPD合并IPA的52例患者诊疗过程与伊曲康唑治疗COPD合并IPA的25例患者诊疗过程。结果两性霉素B治疗COPD合并IPA有效率70.2%,不良反应发生率53.1%,主要是低血钾(44.7%),寒战发热(31.9%),中位疗程29天,治疗经费1820元,7例中途放弃治疗(14.9%);伊曲康唑治疗COPD合并IPA有效率68.4%,不良反应发生率10.5%,均为轻度肝功能异常(5.3%),中位疗程26天,治疗经费28000元,6例中途放弃治疗(24%)。结论与伊曲康唑相比,两性霉素B治疗COPD合并IPA疗效肯定,不良反应发生率高,但无严重不良反应,且治疗经费低,患者能坚持治疗,是较为安全有效的一线抗真菌药物。     

多发性骨髓瘤合并侵袭性真菌感染的临床特点及易感因素分析

目的 了解多发性骨髓瘤(MM)患者合并侵袭性真菌感染(IFI)的临床特点及易感因素.方法 回顾357例在我院住院诊治的MM患者,记录是否合并 IFI、一般临床资料、并发病、抗真菌治疗以及疗效和毒副作用.结果 44例(12.3%)患者在治疗过程中曾发生IFI,其中3例(6.8%)为确诊病例,8例(18.1%)为临床诊断,33例(75.0%)为拟诊.44例患者中,10例(22.7%)处于诱导化疗时出现真菌感染;4例(9.1%)为平台期;27例(61.4%)处于疾病进展状态;3例(6.8%)在行自体造血干细胞移植的过程中发生真菌感染.感染部位以肺部最常见,占50.O%.两性霉素B、伏立康唑、伊曲康唑、卡泊芬净、氟康唑的有效率分别为83.3%、75.O%、78.9%、75.O%和57.1%.各种抗真菌药物之间疗效比较差异无统计学意义(P=0.493).根据多因素分析,合并糖尿病(P=0.035,OR 2.527,95%CI 1.005～6.052),接受透析治疗(P=0.022,OR 2.768,95%CI 1.161～6.600)、粒细胞缺乏持续时间超过1周(P:0.019,OR 3.215,95%CI 1.200～7.407),之前是否使用广谱抗生素治疗(P=0.009,OR 3.350,95%CI 1.353～8.295),是否使用氟达拉滨(P=0.001,OR 4.669,95%CI1.813-12.023)差异有统计学意义.结论 MM患者是侵袭性真菌感染的高危人群,肺部是其最常见的感染部位,4种抗真菌药的疗效相当,合并糖尿病、化疗同时接受透析治疗、长时间粒细胞缺乏、广谱抗生素的应用、以及含有氟达拉滨的治疗是MM合并IFI的易感因素.     

Invasive aspergillosis. Disease spectrum, treatment practices, and outcomes. I3 Aspergillus Study Group

A review of representative cases of invasive aspergillosis was conducted to describe current treatment practices and outcomes. Eighty-nine physicians experienced with aspergillosis completed case forms on 595 patients with proven or probable invasive aspergillosis diagnosed using modifications of the Mycoses Study Group criteria. Pulmonary disease was present in 56%, with disseminated infection in 19%. The major risk factors for aspergillosis were bone marrow transplantation (32%) and hematologic malignancy (29%), but patients had a variety of underlying conditions including solid organ transplants (9%), AIDS (8%), and pulmonary diseases (9%). Overall, high antifungal failure rates occurred (36%), and complete antifungal responses were noted in only 27%. Treatment practices revealed that amphotericin B alone (187 patients) was used in most severely immunosuppressed patients while itraconazole alone (58 patients) or sequential amphotericin B followed by itraconazole (93 patients) was used in patients who were less immunosuppressed than patients receiving amphotericin B alone. Response rate for patients receiving amphotericin B alone was poor, with complete responses noted in only 25% and death due to or with aspergillosis in 65%. In contrast, patients receiving itraconazole alone or following amphotericin B had death due to or with Aspergillus in 26% and 36%, respectively. These results confirm that mortality from invasive aspergillosis in severely immunosuppressed patients remains high even with standard amphotericin B. Improved responses were seen in the less immunosuppressed patients receiving sequential amphotericin B followed by itraconazole and those receiving itraconazole alone. New approaches and new therapies are needed to improve the outcome of invasive aspergillosis in high-risk patients.     

Intravenous and oral itraconazole versus intravenous amphotericin B deoxycholate as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy. A randomized, controlled trial

BACKGROUND: Amphotericin B deoxycholate is currently the standard empirical antifungal therapy in neutropenic patients with cancer who have persistent fever that does not respond to antibiotic therapy. However, this treatment often causes infusion-related and metabolic toxicities, which may be dose limiting. OBJECTIVE: To compare the efficacy and safety of itraconazole with those of amphotericin B as empirical antifungal therapy. DESIGN: An open randomized, controlled, multicenter trial, powered for equivalence. SETTING: 60 oncology centers in 10 countries. PATIENTS: 384 neutropenic patients with cancer who had persistent fever that did not respond to antibiotic therapy. INTERVENTION: Intravenous amphotericin B or intravenous itraconazole followed by oral itraconazole solution. MEASUREMENTS: Defervescence, breakthrough fungal infection, drug-related adverse events, and death. RESULTS: For itraconazole and amphotericin B, the median duration of therapy was 8.5 and 7 days and the median time to defervescence was 7 and 6 days, respectively. The intention-to-treat efficacy analysis of data from 360 patients showed response rates of 47% and 38% for itraconazole and amphotericin B, respectively (difference, 9.0 percentage points [95% CI, -0.8 to 19.5 percentage points]). Fewer drug-related adverse events occurred in the itraconazole group than the amphotericin B group (5% vs. 54% of patients; P = 0.001), and the rate of withdrawal because of toxicity was significantly lower with itraconazole (19% vs. 38%; P = 0.001). Significantly more amphotericin B recipients had nephrotoxicity (P < 0.001). Breakthrough fungal infections (5 patients in each group) and mortality rates (19 deaths in the itraconazole group and 25 deaths in the amphotericin B group) were similar. Sixty-five patients switched to oral itraconazole solution after receiving the intravenous formulation for a median of 9 days. CONCLUSIONS: Itraconazole and amphotericin B have at least equivalent efficacy as empirical antifungal therapy in neutropenic patients with cancer. However, itraconazole is associated with significantly less toxicity.     

A double-blind, randomized, placebo-controlled trial of itraconazole capsules as antifungal prophylaxis for neutropenic patients.

To evaluate the efficacy of itraconazole capsules in prophylaxis for fungal infections in neutropenic patients, we conducted a prospective, double-blind, placebo-controlled, randomized trial. Patients with hematologic malignancies or those who received autologous bone marrow transplants were assigned either a regimen of itraconazole (100 mg orally twice daily; n=104) or of placebo (n=106). Overall, fungal infections (superficial or systemic) occurred more frequently in the placebo group (15% vs. 6%; P=.03). There were no differences in the empirical use of amphotericin B or systemic fungal infections. Among patients with neutropenia that was profound (<100 neutrophils/mm3) and prolonged (for at least 7 days), those receiving itraconazole used less empirical amphotericin B (22% vs. 61%; P=.0001) and developed fewer systemic fungal infections (6% vs. 19%; P=.04). For patients with profound and prolonged neutropenia, itraconazole capsules at the dosage of 100 mg every 12 h reduce the frequency of systemic fungal infections and the use of empirical amphotericin B.     

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).     

几种常用抗真菌药物在恶性血液病合并侵袭性真菌病中的疗效分析

目的探讨临床上常用抗真菌药物在恶性血液病合并侵袭性真菌病(IFD)患者中的总体疗效、分层诊断疗效、疗效与感染部位的关系以及常见毒副反应。方法回顾性分析2005年1月至2008年8月在中山大学附属第一医院住院的117例恶性血液病合并IFD患者的临床资料。结果伊曲康唑、伏立康唑、卡泊芬净和脂质体两性霉素B治疗的总有效率分别为69.0%(40/58)、77.4%(24/31)、64.7%(11/17)和63.6%(7/11)(P=0.726);肺部感染患者中,4种药物的有效率分别为63.0%(17/27)、85.7%(12/14)、50.0%(4/8)和62.5%(5/8)(P=0.283);在肝脾念珠菌病、真菌血症及不明部位感染患者中,各用药组患者疗效相似;6周时各组存活率分别为86.2%、87.1%、70.6%和72.7%。伊曲康唑和伏立康唑常见副反应主要为胃肠道反应和轻度低钾血症,前者副反应有胃肠道反应(12.1%)、低钾血症(20.7%),伏立康唑组个别患者出现视觉异常(9.7%)和椎体外系症状(6.4%);卡泊芬净毒副反应轻微,仅见胃肠道反应(15.4%);脂质体两性霉素B组毒副反应较常见,为寒战发热(81.8%)、低钾血症(100%)、胃肠道反应(18.2%)和肝损害(9.1%)。结论伊曲康唑、伏立康唑、卡泊芬净和脂质体两性霉素B在恶性血液病合并IFD中总体疗效、分层诊断疗效以及6周存活率相当,临床治疗可根据患者特点选择个性化用药方案。     

Fungal colonization in neutropenic patients: a randomized study comparing itraconazole solution and amphotericin B solution

We assessed the impact of prophylaxis with the oral itraconazole solution and amphotericin B solution on fungal colonization and infection in a randomized study among patients with hematological malignancies and neutropenia. Infecting and colonizing Candida strains of patients suffering from candidiasis were genotyped by random amplification of polymorphic DNA (RAPD) analysis. A total of 106 patients were evaluated in this study: 52 patients in the itraconazole and 54 in the amphotericin B arm. During neutropenia fungal colonization in the oropharynx occurred in 11 (19.6%) and 24 (40.6%) and in the rectum in 11 (19.6%) and 23 (38.9%) courses in the itraconazole and amphotericin B groups (P<0.05), respectively. Candida albicans was the most prevalent species in both study groups. Mixed fungal colonization with Candida krusei and Candida glabrata was increased in the amphotericin B group, yet without clinical importance since infections were due to C. albicans. The occurrence of invasive candidiasis was significantly increased in multicolonized compared to monocolonized patients. In the amphotericin B group 20 and in the itraconazole group 2 neutropenic patients showed multicolonization with Candida spp. (P<0.05). Overall fungal infections were 3.8% in the itraconazole and 14.8% in the amphotericin B group (P<0.05). RAPD typing showed oropharynx strains involved in superficial infections in four of five patients. In all four patients with deep fungal infections, it appears that the colonizing rectum strains were identical to infecting strains of Candida spp. Itraconazole solution significantly reduced Candida colonization and infection compared to amphotericin B solution. Most patients remained infected with the colonized strains for the entire study period, irrespective of antifungal prophylaxis.     

Infección fúngica invasora en los pacientes hematológicos

Invasive fungal infection (IFI), caused by both yeasts and moulds, is a persistent problem, with high morbidity and mortality rates among patients on chemotherapy for haematology diseases, and hematopoietic stem cell transplant recipients. Management of IFI in these types of patients has become highly complex with the advent of new antifungals and diagnostic tests, resulting in different therapeutic strategies (prophylactic, empirical, pre-emptive, and targeted). A proper assessment of the risk for IFI of each individual patient appears to be critical in order to use the best prophylactic and therapeutic approach, and to increase the survival rates. Among the available antifungals, the most frequently used are fluconazole, mould-active azoles (itraconazole, posaconazole, voriconazole), candins (anidulafungin, caspofungin, micafungin), and amphotericin B (particularly its lipids formulations). Specific recommendations for use and the criteria for selection of antifungal agents are discussed in this paper.