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。     

伊曲康唑治疗侵袭性真菌感染疗效观察

目的评价伊曲康唑治疗侵袭性真菌感染的有效性和安全性。方法选择2003年9月至2005年9月中国医科大学附属第一医院应用伊曲康唑完整疗程治疗的侵袭性真菌感染患者16例(17例次)。其中确诊1例,疑似11例(12例次),可能感染4例。患者用量第1天至第2天伊曲康唑注射液200mg,每天2次,静脉注射;第3天至第14天:200mg,每天1次,静脉注射;第15天至第42天改用伊曲康唑胶囊或口服液200mg,每天2次。2例患者应用200mg,每天2次,分别静脉注射治疗9d和14d;1例200mg,每天1次,静脉注射治疗21d。结果16例患者共检出真菌菌株62株,其中尿培养40株,热带念珠菌占首位21株。确诊和疑似的12例(13例次)患者中痊愈率6/13,有效率为11/13,真菌清除率6/13。入选22例(24例次)患者中,不良反应发生率3/24。结论伊曲康唑治疗深部真菌感染有效,尤其在危重、高龄患者中长时间应用安全性高。     

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。     

伊曲康唑治疗血液病患者侵袭性真菌感染的多中心回顾性分析

目的 观察伊曲康唑在治疗血液病及造血干细胞移植(HSCT)后患者侵袭性真菌感染(IFI)的疗效和安全性.方法 采取开放、多中心回顾性研究的方法 ,选择2007年1-7月确诊、临床诊断和拟诊IFI的血液病或HSCT患者666例,给予静脉伊曲康唑,按前2天200ms/次、12h静脉滴注1次,第3天起200 ms/次,每天静脉滴注1次的方案治疗,并根据病情序贯伊曲康哗口服液或胶囊.根据临床和微生物学疗效标准,综合评价该药物的疗效,并观察其安全性.结果 全部患者抗真菌治疗的退热有效率为70.1%,治疗有效率为69.5%,其中确诊、临床诊断和拟诊IFI患者的有效率分别为73.7%、68.1%、68.2%,其问差异无统计学意义(P=0.380).全部患者中有58例(8.7%)出现与伊曲康唑相关的不良事件,主要表现为轻中度的肝胆系统和胃肠系统功能受损.结论 伊曲康唑是治疗血液病及HSCT患者IFI有效且安全的药物,适用于抗真菌的经验治疗.     

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.     

伊曲康唑预防和治疗重症血液病患者真菌感染的临床观察

４０例重症血液病患者（生再障２例、急性白血病３３例、非何杰金氏恶性淋巴瘤５例）应用伊曲康唑预防和治疗真菌感染。２０例治疗组患者中，有效１７例（有效率８５％）；２０例预防组患者中，仅１例发生真菌感染（发病率５％（）。与随机分配的患者对照组２０例（发病率３５％）比较有显著性差异（Ｐ〈０．０５）。伊曲康唑副作用轻微。     

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.     

伊曲康唑序贯疗法治疗矽肺合并侵袭性真菌病20例分析

矽肺患者由于常引起肺间质纤维化、毛细血管闭塞、肺气肿形成而导致呼吸功能减退和反复并发感染,因而较频应用抗生素、糖皮质激素以及慢性病情使身体免疫功能减退,给真菌感染提供了条件。现将我院收治的矽肺并真菌感染20例应用伊曲康唑序贯疗法治疗的疗效报道如下。     

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。     

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。     

Management of intracranial fungal infections in patients with haematological malignancies

The incidence of, and mortality associated with, invasive fungal infections remains far higher than hoped. As a consequence of the overall increase in the incidence of such infections over time, the incidence of central nervous system (CNS) fungal infections is also increasing and, despite improvements in diagnostic techniques and the introduction of novel antifungal agents, therapy for CNS infections is still associated with discouragingly poor results. In patients with haematological malignancies, opportunistic infections with Candida or Aspergillus remain the most common infections affecting the CNS; however, opportunistic infections with less well-known fungi are becoming more common and must be considered in the differential diagnosis. New techniques for the early diagnosis of invasive fungal infections are emerging. Pharmacologic options for treating invasive fungal infections have also improved during the past few years, with new drugs becoming available that have broader antifungal spectra and better safety profiles. Other novel treatment approaches, such as combination therapy, are also being explored. Early investigations have produced encouraging results; however, large, prospective studies involving many patients are necessary to validate the widespread use of these approaches. This review analyses the existing guidelines for treatment of CNS fungal infections and the literature available on the use of new drugs to generate sets of recommendations for treatment of these life-threatening infections in patients with haematological malignancies.     

伏立康唑治疗血液病侵袭性真菌感染93例报道

目的观察伏立康唑治疗血液病患者并发侵袭性真菌感染(IFI)的临床疗效及安全性。方法回顾分析2006—2008年天津医科大学总医院住院的93例血液病患者并发IFI的临床表现及使用伏立康唑的疗效和不良反应。结果93例IFI患者中确诊4例(4.3%)、临床诊断76例(81.7%)、拟诊13例(14.0%)。感染部位以肺部为主(87例,占93.5%),鼻腔感染2例(2.2%),血流感染2例(2.2%)、中枢神经系统和肝脏感染各1例。G试验阳性者74例(80.0%)。22例有真菌学依据,其中念珠菌12例(54.5%),曲霉菌7例(32.0%),隐球菌1例(4.5%),其他2例(9.0%)。出现影像学改变者71例(76.3%),以磨玻璃影最多(44例),其次为多发斑片状阴影(13例),不规则多发结节高密度影5例,有晕轮征者4例,有空洞形成者2例,其他改变3例。伏立康唑静脉用药时间平均14d,序贯伏立康唑口服平均20d,总疗程约34d。93例IFI患者治疗有效71例(76.4%),疗效不佳11例(11.8%),死亡11例(11.8%)。其中拟诊组有效率84.6%,临床诊断组有效率77.6%,两者之间差异无统计学意义(P=0...     

Diagnostic challenges and recent advances in the early management of invasive fungal infections

During the past 20 yr, the population of immunocompromized patients at risk of developing invasive fungal infections (IFIs) has increased, and there has been a shift in fungal epidemiology, with more infections caused by non‐Aspergillus molds and yeasts, which are often resistant to one or more antifungal drugs. Traditional diagnostic methods, such as culture and the histopathology of infected tissue, often fail to detect IFIs until the later stages. Furthermore, invasive diagnostic methods to obtain tissue may be contraindicated in severely ill patients; even when tissue is available, the morphology of several filamentous fungi is identical, or the cultures may fail to grow the pathogen. Recently developed non‐invasive diagnostic techniques, such as tests for serum markers and polymerase chain reaction assays, may allow for earlier and more accurate diagnoses – crucial in the effort to reduce morbidity and the risk of mortality. This article reviews current approaches to diagnosis and treatment, focusing on how an early and accurate diagnosis can guide treatment and improve outcomes. Strategies for improving the management of IFIs also are discussed.     

Considerations in the approach to invasive fungal infection in patients with haematological malignancies

Invasive infections because of opportunistic yeasts and moulds have contributed significantly to the morbidity and mortality associated with potentially curative treatment for haematological malignancies. Many risk factors have been identified that permit the clinician to predict the likelihood of these infections. The diagnostic process involves maintaining a high index of suspicion based upon an understanding of the clinical circumstances under which invasive fungal infections occur, of the spectrum of fungal syndromes, and of the advantages and limitations of diagnostic testing strategies now available. Treatment strategies may be categorized as prophylactic, pre-emptive, empiric, or directed based upon the circumstances. The therapeutic options have increased in recent years but are not applicable to all clinical circumstances. These considerations are discussed.     

肝病患者真菌感染的特点及耐药性分析

目的分析肝病患者真菌感染的特点和耐药性,为临床预防真菌感染和合理用药提供依据。方法回顾分析2011年1月—2014年6月临床分离的1472株真菌的组成及耐药性。结果肝病患者真菌感染的主要标本来源是痰、中段尿和腹水。菌种以白假丝酵母菌为主(54.96%),其次是烟曲霉菌(13.25%),热带假丝酵母菌和光滑假丝酵母菌分别为10.39%和10.26%。丝状真菌对抗真菌药的耐药率明显高于酵母菌(P=0.000)。对氟康唑的耐药率较高的为烟曲霉菌(100%)、克柔假丝酵母菌(81.67%)和光滑假丝酵母菌(24.50%),克柔假丝酵母菌对伊曲康唑的耐药率达16.67%,白假丝酵母菌的药物敏感性较好。结论肝病患者真菌感染以白假丝酵母菌为主,其次是烟曲霉菌。不同种的真菌对不同抗真菌药的敏感性不同,临床应根据患者真菌感染和耐药特点合理治疗。     

Caspofungin as first line therapy of pulmonary invasive fungal infections in 32 immunocompromised patients with hematologic malignancies

Invasive Fungal Infections (IFI) remain a severe and major complication among patients with hematologic diseases, but the recent availability of new antifungal agents (echinocandins and new azoles) have improved the chance of cure. Caspofungin (Cancidas-Merck) is a large lipopeptide molecule able to inhibit the enzyme complex 1,3-d-glucan synthetase; this action specifically damages the fungal cell wall. Caspofungin (CAS) is active, in vitro and in vivo, against most Candida species and Aspergillus species. We report on our experience with this drug as first-line therapy for proven or probable pulmonary IFI in immunocompromised patients with hematologic malignancies. Thirty-two consecutive patients (20 males and 12 females, with a median age of 52 yr) have been treated with CAS (27 acute leukemias, 1 chronic leukemia, 3 lymphomas and 1 multiple myeloma). Sixteen patients (50%) had a relapsed or resistant hematologic disease, while 12 patients were in complete remission and 4 were at onset of disease; 8/32 (25%) developed IFI after a hematopoietic stem cell transplant (HSCT) procedure. Seven out of 32 patients (22%) had a proven pulmonary IFI (7/7 Aspergillosis) and 25 (78%) had a probable IFI with pulmonary localization as defined according to international consensus. Thirty-one patients (97%) had less than 1000 granulocytes/mL at onset of infection and at the start of CAS therapy. The CAS was given at the dose of 70 mg on day 1, followed by 50 mg/day. Median duration of CAS therapy was 20 d (range 8-64); all the 31 neutropenic patients received concomitant granulocyte colony-stimulating factor (G-CSF). The overall response rate was 56% (18/32) with 12/18 complete responses and 6/18 partial responses; two patients (6%) had a stable disease. Twelve out of 32 (38%) did not respond and seven died of mycotic infection. Univariate analysis showed that granulocytes recovery (>500/mL vs. <500/mL) and status of hematologic disease (remission/onset vs. refractory/relapsed) were significantly associated to favourable outcome. No clinical adverse events (AE) were reported and only a grades I and II transient increase of serum alkaline phosphatase and/or transaminases occurred in 4/32 (12%) patients. After CAS therapy six non-responders and six cases with a partial or stable response were rescued with voriconazole. Two out of six patients (33%) in the former group and 6/6 (100%) in the latter obtained a complete resolution of IFI. Our experience suggests an efficacy of CAS, in combination with G-CSF, as first-line treatment of proven or probable IFI with pulmonary localization. The drug was well tolerated and there were no significant hepatic AE even in patients receiving CAS with cyclosporine after a HSCT. A significant proportion of non-responders or partial responders to CAS can be rescued with a subsequent voriconazole-based therapy.     

Risk factors for the development of invasive fungal infections in allogeneic blood and marrow transplant recipients

Abstract: Blood and marrow transplantation (BMT) is increasingly used to treat malignant and nonmalignant diseases. Despite significant advances in the management of transplant recipients, however, fungal infections remain important life-threatening complications of BMT. Over the past two decades, the incidence of fungal infections in this population has continued to rise. Several factors predispose BMT recipients to invasive fungal infections. These include but are not limited to use of intensive myeloablative chemotherapy and radiation therapy combined with prolonged granulocytopenia; development of acute and chronic graft-versus-host disease; administration of immunosuppressive therapy, particularly using corticosteroids; use of central venous catheters; and prolonged impairment of cell-mediated immunity secondary to the underlying disease and post-transplant immunodeficiency. Environmental factors also play a key part in the pathogenesis of fungal infections. Therefore, infection-control measures are critical to the prevention of such infections. In addition, although Candida and Aspergillus species are still the major culprits, other opportunistic fungi have emerged in recent years.