米卡芬净在治疗恶性血液病患者侵袭性真菌感染中的应用

目的 评价米卡芬净治疗血液肿瘤患者侵袭性真菌感染（IFI）的疗效及安全性。方法对同期收治的38例恶性血液病并发IFI患者应用米卡芬净治疗,观察疗效及安全性。结果38例总有效率为57．9％（22／38）,确诊、临床诊断与拟诊者有效率分别为75．0％、63．2％、36．4％;38例均未出现临床和实验室不良反应。结论米卡芬净抗菌潜广,临床疗效及安全性好,可作为恶性血液病患者预防、经验性和抢先抗真菌治疗的药物。     

米卡芬净治疗恶性血液病侵袭性真菌感染10例临床分析

米卡芬净(micafungin,商品名mycamine)是由日本藤泽公司开发的一种新型的作用于真菌细胞壁的棘白菌素类抗真菌药物,是继卡泊芬净之后美国食品药品管理局(FDA)批准的第2种棘白菌素类抗真菌药物.     

米卡芬净治疗血液系统恶性疾病合并侵袭性真菌感染疗效和安全性分析

目的 评估米卡芬净治疗中国侵袭性真茵感染患者(IFI)的疗效和安全性.方法 造反007年4～12月全国15家医院的60例合并IFI的血液系统恶性疾病患者入选本研究.侵袭性真茵感染的诊断为确诊、临床诊断和高危疑似.入选患者接受150 mg/d的米卡芬净治疗,剂量可以调整至50～150 mg/d.治疗持续时间不短于7 d.结果 53.3%(33/60)患者治疗有效.治疗的耐受性较好,最常见的不良反应是肝功能异常,包括胆红素和转氨酶升高,但均为轻度.1例患者因过敏退出研究.结论 米卡芬净是治疗血液系统恶性疾病合并IFI的有效药物,耐受性也较好.     

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。     

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。     

卡泊芬净治疗恶性血液病并发侵袭性真菌感染患者的疗效观察

恶性血液病患者因接受大剂量化疗,应用免疫抑制剂及广谱强效抗生素,造成中性粒细胞严重减少,免疫功能明显下降,极易发生侵袭性真菌感染(IFI)。抗真菌治疗疗程长,而多数并发真菌感染者的基础疾病重,对药物耐受性差,老年患者更为突出。我院采用卡泊芬净治疗恶性血液病并发IFI患者41例,观察其疗效和安全性,报告如下。     

伏立康唑治疗血液病合并侵袭性真菌病61例临床观察

目的:观察伏立康唑治疗血液病合并侵袭性真菌感染(IFD)患者的疗效。方法:回顾性分析61例伏立康唑治疗血液病合并IFD患者的临床资料。结果:足量足疗程的伏立康唑治疗血液病合并IFD的总有效率为67.2%,其中预防治疗31例中24例(77.4%)有效,经验治疗24例中13例(54.2%)有效,两者的差异无统计学意义(P0.05)。9例患者用药后出现肝功能轻度异常,2例出现皮疹,1例出现恶心呕吐,均不影响治疗。结论:足量足疗程的伏立康唑治疗血液病合并IFD患者有一定疗效,不良反应较少。     

卡泊芬净治疗恶性血液病合并侵袭性肺部真菌感染的临床疗效观察

目的 观察卡泊芬净在恶性血液病患者肺部真菌感染治疗中的疗效及安全性.方法 回顾性分析我科2007年10月～2014年1月间49例恶性血液病合并侵袭性肺部真菌感染患者的临床资料,评估其静脉应用卡泊芬净治疗的临床疗效,并于治疗期间监测肺部影像学、肝肾功能等.结果 49例患者中,临床诊断10例,拟诊39例;卡泊芬净治疗7 d ～ 210 d,总有效率为53.6％;临床诊断10例患者中,临床治愈0例,临床显效4例,进步2例,无效4例,有效率为40％;拟诊39例患者中,临床治愈8例,临床显效14例,进步8例,无效9例,有效率为56.4％;初始治疗组37例,有效率54.5％,挽救性治疗组12例,有效率50.0％;仅1例患者在治疗期间出现一过性谷丙转氨酶增高,至67 IU/L,其他患者用药过程中均未出现明显不良反应.结论 卡泊芬净治疗恶性血液病患者合并侵袭性肺部真菌感染患者具有一定疗效且安全性好.     

米卡芬净治疗免疫功能低下患者侵袭性真菌感染的疗效及安全性分析

侵袭性真菌感染(IFI)是引起免疫功能缺陷的患者死亡的主要原因之一,寻找高效低毒的抗真菌药物对于提高免疫功能缺陷患者的长期存活十分重要。米卡芬净(mica-fungin)是一种1,3-β-D-葡聚糖合成酶抑制剂,其抗菌谱广,在体内、外对曲霉菌、念珠菌均有抗菌活性[1]。我们对7例IFI的患     

老年恶性血液病合并真菌感染20例临床分析

目的提高对老年恶性血液病患者合并真菌感染的认识,完善治疗措施,减少真菌感染率、死亡率,提高生存率。方法分析住院的老年恶性血液病合并真菌感染患者20例的一般临床资料、病原微生物学检查及治疗情况。结果老年血液肿瘤患者真菌感染的发病率不断增高,病原菌以念珠菌为主,20例患者应用抗真菌药物后总有效率为55％,死亡率为25％。结论真菌感染是老年恶性血液病患者化疗期间严重的并发症和主要的死亡原因之一,早期诊断、经验治疗,具有重要意义;对于高危患者,预防治疗尤为必要。     

Significant alterations in the epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies

Invasive fungal infections (IFI) remain a leading cause of morbidity and mortality in immunocompromised patients. This retrospective single-center study analyzed incidence, treatment and outcome of invasive fungal infections in 1,095 patients with hematological malignancies receiving either cytoreductive chemotherapy or autologous or allogeneic hematopoietic stem cell transplantation at our institution between 1995 and 2004. IFI occurred in 167/1,095 (15%) patients with a significant increase over time (12.7% between 1995 and 2000 vs. 18.1% in the later IFI cohort, P = 0.0134). Fifty-four (32%) patients had proven, 70 (42%) patients had probable, and 43 (26%) patients suffered from possible IFI according to EORTC/MSG criteria. In 108/124 (87%) cases with proven or probable IFI, moulds were the causative pathogens. Both, Aspergillus fumigatus (n = 46) and Aspergillus terreus (n = 41) were predominant. Yeast infections (Candida spp.) were documented in 16/124 (10%) cases with proven or probable IFI. Median overall survival of the entire IFI cohort was 7 (3–17) months. Overall survival was significantly better in patients with probable or possible IFI (37 and 38%, respectively) compared with patients with proven IFI (28%, P = 0.019). In 35% of patients, IFI was the principal cause of death with a significant decrease over time (44% in time cohort 1995–2000 vs. 28% in the later IFI cohort, P = 0.018) accompanied by an increased use of novel antifungals. By multivariate analysis, only proven IFI was significantly predictive for death (HR 1.7, P = 0.018). A significant decrease in fungus-related deaths was observed despite a significant increase of IFI over time, probably due to improved diagnostic and therapeutic approaches.     

卡泊芬净经验性治疗血液疾病合并真菌感染32例临床观察

目的:评估卡泊芬净经验性治疗血液疾病中性粒细胞减少合并疑似侵袭性真菌感染的安全性和疗效。方法:入选32例发热合并中性粒细胞缺乏、基础疾病为血液系统恶性肿瘤的患者。给予卡泊芬净经验性治疗,第1天70 mg,加入生理盐水250 mL,静脉滴注,持续1 h,随后每天50 mg,加入生理盐水250 mL,静脉滴注,持续1 h。治疗持续时间为体温好转、粒细胞缺乏恢复后继续使用3 d;若患者粒细胞缺乏期间体温未好转,最长使用2周。结果:23例(72%)患者在中性粒细胞减少期间体温好转。主要不良事件是转氨酶升高(4/32)和低钾血症(4/32),经治疗均好转。3例患者死亡。所有患者治疗期间均未发生突破性真菌感染事件。结论:卡泊芬净是血液疾病合并真菌感染经验性治疗安全和有效的药物。     

血液系统肿瘤院内真菌感染的临床分析

目的探讨血液系统肿瘤患者院内真菌感染的现状,分析其危险因素及预防措施。方法对2006年1-12月间经微生物学检查证实的70例血液系统肿瘤合并院内真菌感染患者的临床资料及真菌培养结果进行统计分析。结果真菌感染部位以呼吸道为主(88.57%),胃肠道次之(7.14%);感染菌株以白假丝酵母菌占首位(56.96%),其次为克柔假丝酵母菌(12.66%)、光滑假丝酵母菌(11.39%)。结论本组患者院内真菌感染与原发基础疾病、反复化疗、粒细胞减少、老龄化、广谱抗生素及免疫抑制剂的应用等危险因素密切相关。     

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。     

米卡芬净治疗急性白血病患者合并侵袭性真菌感染的疗效和安全性

目的 研究150 mg/d米卡芬净治疗急性白血病患者合并侵袭性真菌感染(IFI)的疗效和安全性.方法 133例急性白血病合并IFI患者,以米卡芬净150 mg/d连续治疗14 d,在治疗第(7±2)天及第(14±2)天评估临床疗效及真菌学疗效,并记录药物不良反应.正态分布数据比较采用方差分析,非正态分布数据采用Wilcoxon秩和检验.结果 133例急性白血病合并IFI患者中,116例完成了14 d的米卡芬净治疗.急性白血病合并IFI患者(14±2)d 临床疗效总体改善率为94.8%,真菌学疗效总体清除率为75.0%,其中对念珠菌的清除率为82.9%,对曲霉菌的清除率为66.7%,其他真菌的清除率为55.6%,两者均明显好于(7±2) d(83.6%,21.4%),差异有统计学意义(X2=6.060、34.416,均P<0.05).临床疗效与年龄、性别、IFI诊断、白血病类型及是否合并用药无关(X2=26.541,P<0.05).133例患者的药物相关不良反应发生率为3%,主要为皮疹3例、腹泻1例,除1例因皮疹严重而停药外,其余均可耐受.结论 150 mg/d米卡芬净治疗14 d对急性白血病合并IFI患者具有良好的疗效及安全性.

Abstract：

Objective To evaluate the efficacy and safety of micafungin in the treatment of invasive fungal infections (IFI) in patients with acute leukemia.Methods A total of 133 IFI patients with acute leukemia received micafungin 150 mg once daily for 14 days.The clinical and mycological efficacies were evaluated on (7±2) days and(14±2) days of treatment.Meanwhile,the adverse events were recorded.The normally distributed data was compared using analysis of variance and nonnormal distributed data was analyzed using Wilcoxon rank-sum test.Results Among 133 IFI patients with acute leukemia,116 finished the 14-day micafungin treatment.The total clinical efficacy was 94.8% and the total mycological efficacy was 75.0% at (14±2) days of treatment.The fungus eliminate rates were 82.9%,66.7% and 55.6% against Monilia,Aspergillus and others,respectively.The clinical and mycological efficacies of (14±2)-day treatment were both higher than those of (7±2)-day treatment(X2=6.060,34.416.both P<0.05).The clinical efficacy was not related with age,sex,IFI diagnose,types of leukemia and combinative drugs (X2=26.541,P<0.05).The incidence of drug-related adverse events of micafungin was 3%among 133 patients,which included skin rash in 3 eases, diarrhea in 1 case. Only one case was discontinued because of severe skin rash and micafungin was well tolerant in other patients. Conclusion Treatment of micafungin 150 mg daily for 14 days is effective and safe in IFI patients with acute leukemia.     

伊曲康唑预防血液肿瘤患者粒细胞减少期并发真菌感染的疗效观察

目的:探究应用伊曲康唑口服液预防血液肿瘤患者化疗后粒细胞减少期并发真菌感染的效果.方法:将62例化疗后中性粒细胞减少的血液肿瘤患者随机分为真菌感染预防用药组和对照组,其中预防用药组患者预防性地服用伊曲康唑口服液,而对照组患者未接受任何预防性抗真菌药物治疗.观察并比较2组患者真菌感染的发生率和严重程度.结果:31例服用伊曲康唑口服液患者中,仅2例发生真菌感染,真菌感染率仅为6.5%,而对照组31例中,8例并发真菌感染,包括3例深部真菌感染,真菌感染率为25.8%,明显高于预防用药组(P<0.01),而且2组患者并发真菌感染的病原菌存在明显差异.结论:预防性应用伊曲康唑口服液能有效降低血液肿瘤患者化疗后粒细胞减少期真菌感染的概率.     

Evaluating the role of prophylaxis in the management of invasive fungal infections in patients with hematologic malignancy

Invasive fungal infection (IFI) is a persistent problem among critically ill and immunocompromised patients, especially hematopoietic stem cell transplant or solid organ transplant recipients, or patients on intensive chemotherapy for acute leukemia. Although numerous antifungal agents are available, IFI remains a serious problem because of obstacles to timely diagnosis and high morbidity and mortality rates associated with such infection. Improvements in treatment of underlying diseases have rapidly expanded the patient populations at risk for IFI with increased use of immunosuppressants, aggressive chemotherapy, broad-spectrum antibiotics, and narrow-spectrum antifungal prophylaxis. There are various treatment strategies that can be used to manage IFI: prophylaxis, empiric, preemptive, and directed. As the infection progresses, the prospect of successfully treating an infection diminishes; conversely, the earlier the intervention, the greater the possibility of unnecessary treatment. This article discusses the epidemiology of the most important fungal pathogens, identifies high-risk patient groups and risk factors associated with IFI, and critically evaluates the advantages and disadvantages of available diagnostic tests and treatment strategies and the rationale for antifungal prophylaxis. For patients at high risk for IFI, antifungal prophylaxis is an attractive strategy, and numerous randomized, controlled clinical studies have documented the benefit of such prophylaxis as well as the most efficacious of currently available agents.     

Newer antifungal agents for invasive fungal infections in patients with haematological malignancy

Since 2001 five new systemically administered antifungal agents have been approved for clinical use. This represents a major advance for antifungal therapy in haematological malignancy patients undergoing chemotherapy or haematopoietic stem cell transplant (HSCT). The echinocandins are a new class of antifungals with a novel mode of action. Capsofungin has already established itself as a valuable therapy for candidaemia and salvage therapy of invasive aspergillosis. Although both anidulafungin and micafungin are approved for treatment of candidiasis, their role in invasive aspergillosis requires more clinical trial evaluation. Of the two newer triazoles, voriconazole has been recommended in international guidelines as primary therapy for acute invasive aspergillosis. Posaconazole has a broad spectrum of activity in vitro and a potentially key role in antifungal prophylaxis in high-risk HSCT recipients and during prolonged neutropenia. Although some of these drugs have important interactions with other medications, and potential toxicities, they are safer to use and more efficacious than amphotericin B deoxycholate. Their arrival gives more choices to treat rarer mycoses and will facilitate clinical trial assessment of combination therapy of aspergillosis where single agent therapy gives less than 50% success rates.