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.     

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。     

伊曲康唑注射液治疗真菌感染17例临床分析

目的评价伊曲康唑注射液治疗侵袭性肺部真菌感染(IPFI)的疗效。方法收集广东省人民医院呼吸科2006年使用伊曲康唑注射液治疗侵袭性肺部真菌感染患者17例,对其疗效进行分析研究。PFI诊断根据“IPFI的诊断标准与治疗原则(草案)”,确诊病例9例,临床诊断5例,拟诊病例3例。结果17例患者中共培养出真菌14株,包括白色念珠菌5株,曲霉菌6株,未分类真菌3株。在接受治疗的17例患者中,痊愈9例,显效2例,进步3例,无效(死亡)3例,总有效率为64.7%。12例接受氟康唑针剂治疗后改为伊曲康唑者9例有效,3例死亡。死亡的3例中2例为肾移植术后感染,1例为糖尿病酮症酸中毒的患者。在治疗过程中仅3例患者有轻微恶心、呕吐,未观察到严重的副反应。结论伊曲康唑注射液是治疗侵袭性肺部真菌感染有效的药物,临床上可作为一线用药治疗使用。     

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。     

恶性血液病合并侵袭性真菌感染76例临床观察

  目的 探讨恶性血液病合并侵袭性真菌感染（IFI）的易感因素、临床特点、疗效和不良反应。方法 回顾性分析76例恶性血液病合并IFI患者的易感因素、临床特点,比较伊曲康唑与两性霉素B的疗效及安全性。结果 76例恶性血液病合并IFI患者应用广谱抗生素者68例（89.5%）,化疗2个疗程以上者64例（84.2%）,中性粒细胞缺乏者43例（56.6%）,长期应用糖皮质激素者34例（44.7%）,中心或外周静脉置管者27例（35.5%）。伊曲康唑和两性霉素B治疗恶性血液病合并IFI的总有效率为60.5%和61.5%（P=0.929）;两组间不良反应对比只在低钾血症方面有差异（14.0%比42.4%,P=0.005）。结论 化疗、应用广谱抗生素、中性粒细胞缺乏等是恶性血液病合并IFI的易感因素。伊曲康唑治疗恶性血液病IFI疗效与两性霉素B相当,但不良反应较少且轻微。     

伊曲康唑预防AECOPD继发肺部真菌感染疗效观察

目的观察伊曲康唑口服（0.2qd）预防AECOPD继发肺部真菌感染疗效及安全性。方法将168例AECOPD患者随机分为三组,A组在常规治疗基础上加用伊曲康唑0.2口服,每天一次;B组在常规治疗基础上加用氟康唑0.2口服,每天一次;C组仅给予常规治疗,三组分别于用药后7天和14天留取痰液行真菌培养,并观察不良反应。结果 A组肺部真菌总感染率为19.30%;B组肺部真菌总感染率为36.36%;C组肺部真菌总感染率为67.86%,A与B、B与C及A与C两组间比较有显著性差异（P〈0.05）。三组均无不良反应发生。结论伊曲康唑口服（0.2qd）预防AECOPD继发肺部真菌感染疗效确切,优于氟康唑,且使用安全。     

肾移植术后真菌性肺炎的诊断及治疗

报道16例肾移植术后真菌性肺炎患者，感染真菌为白色念球菌10例，克柔念珠菌、平滑念珠菌、光滑念珠菌、曲霉菌、毛霉菌各1例。应用氟康唑治疗7例，伊曲康唑1例，两性霉素B脂质体3例。治愈11例，死亡5例。表明肺部真菌感染是肾移植术后的严重并发症，其病死率高，早期诊断和治疗效果较好。     

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。     

74例肺结核继发肺部真菌感染情况分析

目的　探讨山东省结核防治医院肺结核继发肺部真菌感染的危险因素、临床特点及诊治方法。方法 收集2002年1月—2004年9月间山东省5家结核病防治医院临床细菌培养及鉴定获得的真菌感染病例74例并进行分析。结果 74例真菌感染中致病菌以念珠菌居多,其中白色念珠菌52例,占70.3%;光滑念珠菌9例,占12.2%;热带念珠菌5例,占6.8%;克柔念珠菌3例,占4.1%。另外还有少数近平滑念珠菌、葡萄牙念珠菌及隐球菌、曲霉菌、毛霉菌。采用科玛嘉念珠菌显色培养基,据菌落颜色判定菌种并通过ROSCO纸片扩散法,在规定时间内测定抑菌圈的直径,确定真菌菌株的敏感(S)、中介(I)与耐药(R)情况。以两性霉素B、氟胞嘧啶、氟康唑、伊曲康唑及酮康唑为对照药物,白色念珠菌敏感性较好,克柔念珠菌耐药率相对较高。感染的诱发因素多与应用抗生素和激素有关。结论 肺结核较易继发真菌感染,应加强抗生素及肾上腺皮质激素的规范应用,以减少真菌感染及其耐药率的发生,有利于结核病控制及减少死亡。     

127例肺部真菌感染的临床分析

目的 探讨肺部真菌感染发病的易患因素、临床特征、治疗和预后。方法 应用回顾性调查的方法对１２７例肺部真菌感染患者进行分析。结果 ９５％（１２０／１２７）的病例患有基础疾病。其中以慢性阻塞性肺疾病（ＣＯＰＤ）、系统性红斑狼疮、白血病和慢性肾病为多见。肿瘤性疾病也占有重要位置,原发性肺部真菌感染少见。肺部真菌感染的临床表现无特异性。Ｘ线表现以支气管肺炎多见（６１％）,病原菌主要以酵母菌属为主（７９．５     

Intra-abdominal fungal infections complicating acute pancreatitis: a review

Intra-abdominal infections of pancreatic or peripancreatic necrotic tissue complicate the clinical course of severe acute pancreatitis (SAP) and are associated with significant morbidity. Fungal infection of necrotic pancreatic tissue is increasingly being reported. The incidence of intra-abdominal pancreatic fungal infection (PFI) varies from 5% to 68.5%. Candida albicans is the most frequently isolated fungus in patients with necrotizing pancreatitis. Prolonged use of prophylactic antibiotics, prolonged placement of chronic indwelling devices, and minimally invasive or surgical interventions for pancreatic fluid collections further increase the risk of PFI. Computed tomography- or ultrasound-guided fine-needle aspiration of pancreatic necrosis is a safe, reliable method for establishing pancreatic infection. Amphotericin B appears to be the most effective antifungal treatment. Drainage and debridement of infected necrosis are also critical for eradication of fungi from the poorly perfused pancreatic or peripancreatic tissues where the antifungal agents may not reach to achieve therapeutic levels. Fungal infection adversely affects the outcome of patients with SAP and is associated with increased morbidity, although the mortality rate is not increased specifically because of PFI. Although antifungal prophylaxis has been suggested for patients on broad-spectrum antibiotics, no randomized controlled trials have yet studied its efficacy in preventing PFI.     

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.     

HIV/AIDS合并深部真菌感染的调查与耐药研究

目的：了解艾滋病病毒／艾滋病(HIV／AIDS)合并深部真菌感染的临床状况、病原菌分类及耐药现状。方法：总结近年来收治的131例HIV/AIDS患者的临床资料，分析深部真菌感染的发生情况及药敏试验结果。结果：HIV／AIDS患者合并深部真菌感染48例，感染率为36．6％，其中以念珠菌为主，占61％，感染部位以消化道为主，占62．7％。随着CD4^ T淋巴细胞的减少，合并深部真菌感染的感染率逐渐增加。念珠菌对益康唑(ECO)、酮康唑(KET)、咪康唑(MIC)、制霉菌素(NYS)、氟康唑(FLU)、伊曲康唑(ITR)、5-氟胞嘧啶(5-FC)、两性霉素B(AMB)耐药率分别为69．4％、66．7％、58．3％、44．4％、43．8％、36．4％、14．3％、13．9％。结论：HIV／AIDS患者合并深部真菌感染率高，且多有药耐药性，特别是对咪唑类抗真菌药物已呈明显耐药，应引起临床医生的高度警惕。     

Treatment options of invasive fungal infections in adults

A panel of infectious disease specialists, clinical microbiologists and hospital epidemiologists of the five Swiss university hospitals reviewed the current literature on the treatment of invasive fungal infections in adults and formulated guidelines for the management of patients in Switzerland. For empirical therapy of Candida bloodstream infection, fluconazole is the drug of choice in non-neutropenic patients with no severe sepsis or septic shock or recent exposure to azoles. Amphotericin B deoxycholate or caspofungin would be the treatment option for patients with previous azole exposure. In neutropenic patients, empirical therapy with amphotericin B deoxycholate is considered first choice. In patients with severe sepsis and septic shock, caspofungin is the drug of first choice. For therapy of microbiologically-documented Candida infection, fluconazole is the drug of choice for infections due to C. albicans, C. tropicalis or C. parapsilosis. When infections are caused by C. glabrata or by C. krusei, caspofungin or amphotericin B deoxycholate are first line therapies. Treatment guidelines for invasive aspergillosis (IA) were stratified into primary therapy, salvage therapy and combination therapy in critically ill patients. Voriconazole is recommended for primary (ie upfront) therapy. Caspofungin, voriconazole (if not used for primary therapy) or liposomal amphotericin B are recommended for salvage therapy for refractory disease. Combination therapy with caspofungin plus voriconazole or liposomal amphotericin B should be considered in critically ill patients. Amphotericin B deoxycholate is recommended as initial therapy for the empirical therapy in patients with neutropenia and persistent fever with close monitoring of adverse events.     

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。     

肺结核并发真菌感染危险因素及药物敏感性情况分析

目的探讨肺结核并发真菌感染的危险因素及药物敏感性(药敏)情况,为该病的预防、诊断和治疗提供依据。方法选取2011年5月—2012年5月在本院住院治疗的肺结核患者179例,按真菌感染情况分为非真菌感染组(108例)和真菌感染组(71例)。分析2组的临床特点,采用酵母菌显色培养基判断菌种,应用ROSCO纸片扩散法进行药敏分析。结果肺结核并发真菌感染的危险因素为继发性肺结核、复治、痰涂片抗酸染色阴性、长期使用糖皮质激素和广谱抗生素以及合并基础疾病(OR均≥2)。导致肺部真菌感染的主要真菌为假丝酵母菌(87.32%),其中白色假丝酵母菌耐药率低,只有7株对5-氟胞嘧啶耐药;10株热带假丝酵母菌中各有2株对益康唑和两性霉素B耐药;光滑假丝酵母菌只对伊曲康唑敏感。结论①对继发性肺结核、复治、长期使用糖皮质激素和广谱抗生素以及合并基础疾病的肺结核患者要注意肺部真菌感染的预防治疗;②痰涂片抗酸染色阴性可作为早期诊断敏感指标;③对已感染真菌的肺结核患者要行药敏试验,选取最佳抗真菌药物,对光滑假丝酵母菌感染者应提高警惕。     

Role of CT-guided percutaneous lung biopsy in diagnosis of pulmonary fungal infection in patients with hematologic diseases

The goal of our study is to evaluate the efficiency and safety of CT-guided percutaneous lung biopsy for the diagnosis of pulmonary fungal infection in patients with hematologic disease. Medical records were retrospectively reviewed for 16 patients with hematologic diseases, who were initially suspected to have pulmonary fungal infection clinically and underwent further diagnostic methods including blood culture, sputum culture and percutaneous lung biopsy. Of the 16 patients, 10 were diagnosed fungal infection (8 aspergillus, 2 mold fungus), 4 chronic organizing pneumonitis, 1 tuberculosis, and 1 Pneumocystis carinii through histological examination after percutaneous lung biopsy. However, the results of blood culture and sputum culture were negative. CT-guided biopsy showed 100% overall accuracy and 62.5% (10/16) fungal infection rate. The biopsy-induced complications encountered were pneumothorax in 3/16 (18.75%) and hemoptysis in 1/16 (6.25%). No serious complication was found in this series. In conclusion, CT-guided percutaneous lung biopsy is an effective and safe method for the diagnosis of pulmonary fungal infection in patients with hematologic diseases.