儿童肺部侵袭性真菌感染93例临床回顾性分析

目的探讨儿童肺部侵袭性真菌感染的临床表现、治疗与预后。方法回顾性分析广州医科大学附属第一医院儿科2012年1月至2018年8月93例拟诊及确诊为肺部侵袭性真菌感染的儿童患者的临床表现、影像学表现、实验室检查、治疗及预后。结果93例真菌患者中男64例,女29例;年龄(55.18±5.38)个月,年龄范围为1个月至15岁,中位年龄32个月。所有患儿平均住院天数为25.4 d,住院天数中位数为23 d。所有患者临床表现无特异性,主要表现为发热、咳嗽、咳痰、气促、呼吸困难。肺部影像学表现形态多样,主要为肺纹理稍增粗/增多,纹理间可见斑点或斑片状模糊影,并伴有肺实变、弥漫性结节样变等,支气管扩张及纵隔淋巴结肿大较少见。93例患者中血/深部痰真菌培养阳性者41例(44.1%),其中念珠菌属阳性者22例(53.6%)部分患者同时培养出2种不同真菌。93例患儿中,抗真菌治疗有效72例(77.4%),因基础疾病严重放弃治疗8例(8.6%),转院治疗6例(6.5%),死亡7例(7.5%)。其中,单用或联合使用伏立康唑抗真菌感染41例(44.1%),有效38例(92.7%),死亡3例(7.3%)。结论儿童肺部侵袭性真菌感染好发于伴有严重基础性疾病的患儿,其临床表现及影像学表现无特异性,病死率和预后与宿主因素、环境因素及抗真菌治疗密切相关,使用伏立康唑抗真菌治疗能有效降低儿童肺部真菌感染的病死率。     

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。     

异基因造血干细胞移植后肺部侵袭性真菌感染现行诊断标准的应用价值

  目的 分析我国现行血液病/恶性肿瘤患者侵袭性真菌感染诊断标准的可操作性,提高对异基因造血干细胞移植（allo-HSCT）后肺部侵袭性真菌感染特点的认识。方法 回顾性分析连续收治的51例allo-HSCT后肺部侵袭性真菌感染病例的临床特点。结果 肺部侵袭性真菌感染共占同期收治allo-HSCT后肺部感染病例的42.1%（51/121）。确诊1例（2.0%）,临床诊断24例（47.1%）,拟诊26例（51.0%）。使用免疫抑制剂、糖皮质激素和存在移植物抗宿主病为主要宿主因素。2种或2种以上宿主因素同时存在的病例占66.7%(34/51)。94.1%(48/51)病例的肺部高分辨CT表现为结节和（或）斑片影。真菌抗原检测阳性率相对较高［(1,3)-β-D葡聚糖（G）试验阳性率58.6%,半乳甘露聚糖（GM）试验阳性率33.3%］。20例（39.2%）患者伴有动脉血氧分压和氧饱和度下降。结论 使用免疫抑制剂、糖皮质激素和存在移植物抗宿主病为主要宿主因素,肺部高分辨CT表现以结节和（或）斑片影多见,真菌抗原检测是支持临床诊断的主要因素。     

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.     

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.     

血液病患者真菌感染二级预防现状

侵袭性真菌感染（IFI）在恶性血液病患者中发病率和死亡率均较高。近年来,对侵袭性真菌感染早期诊断的进步和新的有效药物的应用提高了恶性血液病患者首次抗真菌治疗的疗效,使更多患者获得再次化疗和造血干细胞移植的机会。但既往确诊或临床确诊侵袭性真菌感染的血液病患者再次接受免疫抑制剂治疗或细胞移植时真菌感染复发的危险性增加,死亡率极高。因此,采取措施预防真菌感染的再发,即真菌感染的二级预防成为必然要求。真菌感染的二级预防已成为广大医务工作者的共识。     

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.     

ELISA法血清半乳甘露聚糖及甘露聚糖检测诊断侵袭性真菌病

近年来,血液肿瘤患者的侵袭性真菌感染(IFI)发生率显著增高,其在血液病患者的治疗中已成为一个亟待解决的问题。1999—2003年,意大利对全国18个血液病治疗中心的11802例患者进行的回顾性调查发现,确诊及高度可疑的IFI占总病例的4.6%;真菌感染占总IFI的64.3%,酵母菌感染占35.7%;     

血液病/恶性肿瘤患者侵袭性真菌病的诊断标准与治疗原则(第四次修订版)解读

侵袭性真菌感染(invasive fungal infection,IFI)是血液病/恶性肿瘤患者主要的感染并发症及致死原因之一.国内外流行病学研究均显示血液病患者侵袭性真菌感染发病率呈现上升趋势,而且IFI的临床确诊困难,延迟治疗又会导致死亡率升高.临床研究显示念珠菌和曲霉菌感染死亡率近40％ ～ 50％,严重影响血液病/恶性肿瘤患者的长期生存[1-4].中国侵袭性真菌感染工作组参照欧美标准制定了我国侵袭性真菌感染的诊断标准与治疗原则(下称指南),并先后进行了二次修订,提高了国内血液病/恶性肿瘤患者侵袭性真菌感染的诊断和治疗水平[5].在既往指南的基础上,结合近年来国内血液病/恶性肿瘤真菌感染流行病学和临床治疗的最新进展和国外指南,经过反复讨论,工作组制定了中国血液病/恶性肿瘤患者侵袭性真菌病的诊断标准与治疗原则.笔者就新版指南的主要特点,特别是重要的概念更新,做进一步的分析和解读.     

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。     

血清1,3-β-D葡聚糖和半乳甘露聚糖抗原联合检测对血液肿瘤患者侵袭性真菌感染的早期诊断价值

目的：评价血清1,3—β-D葡聚糖（G）和半乳甘露聚糖（GM）抗原联合检测对血液肿瘤患者侵袭性真菌感染（IFI）的早期诊断价值。方法：42例中性粒细胞减少伴发热,经广谱抗生素治疗无效的血液病患者,根据临床回顾性诊断标准定义阳性和阴性病例。采用ELISA试剂盒检测患者血清G和GM,分别计算GM试验和G试验及联合检测的灵敏度、特异度、阳性和阴性预测值。结果：以I值〉1．0为GM试验阳性,G浓度〉60pg／L为G试验阳性计算,GM试验和G试验联合检测的灵敏度、特异度、阳性和阴性预测值77．8％,90．3％,82．4％,87．5％;G试验的灵敏度和阳性预测值高,但GM试验的特异度高。结论：GM试验和G试验联合检测提高试验的敏感度,减少了假阴性的发生,对早期诊断IFI有一定的临床意义。     

Treatment of invasive fungal infections in clinical practice: a multi-centre survey on customary dosing,treatment indications,efficacy and safety of voriconazole

Invasive fungal infections are frequent and often deadly complications in patients with malignant hematological diseases. Voriconazole is a third generation triazole antifungal with broad activity against most clinically relevant fungal pathogens. Clinical practice often deviates from insights gained from controlled randomized trials. We conducted a multi-centre survey to evaluate efficacy, safety, treatment indications and dosing of voriconazole outside clinical trials. Patients receiving voriconazole were documented via electronic data capturing. An analysis was conducted after submission of 100 episodes from September 2004 to November 2005. Voriconazole was administered for suspected or proven invasive fungal infection (IFI) (57%), as empirical treatment in patients with fever of unknown origin (21%) and secondary (19%) as well as primary (3%) prophylaxis of IFI. Investigators’ assessment of fungal infection often diverted from EORTC/MSG 2002 criteria. A favorable response was reported in 61.4% for suspected or proven IFI and 52.4% for empirical treatment. Mortality was 15%, 26.7% of which was attributable to IFI. Breakthrough fungal infections occurred in four (21.1%) patients with voriconazole as secondary prophylaxis. Toxicity and adverse events comprised elevated liver enzymes and visual disturbances. Although indications frequently deviated from clinical evidence and legal approval, voriconazole showed efficacy and safety, comparable to major controlled clinical trials. Data from this survey demonstrate the difficulty of putting drugs to their approved use in IFI.     

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.     

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.     

Efficacy of caspofungin as secondary prophylaxis in patients undergoing allogeneic stem cell transplantation with prior pulmonary and/or systemic fungal infection

Transplanted patients with a history of invasive fungal infection (IFI) are at high risk of developing relapse and fatal complications. Eighteen patients affected by hematological malignancies and a previous IFI were submitted to allogeneic stem cell transplantation, using Caspofungin as a secondary prophylaxis. Patients had a probable or proven fungal infection and 16 had a pulmonary localization. No side effects were recorded during treatment with Caspofungin. Compared to pre-transplant evaluation, stability or improvement of the previous IFI was observed in 16 of the 18 patients at day 30, in 13 of the 15 evaluable patients at day 180 and in 11 of the 11 evaluable patients at day 360 post transplant. In particular, all the six patients with a proven fungal infection were alive, with a stable or improved IFI after 1 year from transplant. At a maximum follow-up of 31 months, eight patients died for disease progression or transplant-related complications, but only two had evidence of fungal progression. Secondary prophylaxis with Caspofungin may represent a suitable approach to limit IFI relapse or progression, allowing patients with hematological malignancies to adhere to the planned therapeutic program.     

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...     

1,3-Beta-D-glucan antigenemia for early diagnosis of invasive fungal infections in neutropenic patients with acute leukemia.

BACKGROUND: Invasive fungal infections (IFIs) are life-threatening complications in neutropenic patients with hematological malignancies. Because early diagnosis of IFI is difficult, new noninvasive, culture-independent diagnostic tools are needed to improve clinical management. Recent studies have reported that detection of 1,3-beta-D-glucan (BG) antigenemia may be useful for diagnosis of IFI. The aim of the present prospective study was to evaluate the usefulness of monitoring BG in patients undergoing chemotherapy for acute leukemia. METHODS: BG antigenemia was measured by a colorimetric assay twice weekly in the absence of fever and daily in the presence of fever. IFIs were classified according to the criteria of the European Organization for Research and Treatment of Cancer/Mycoses Study Group. RESULTS: During 190 consecutive neutropenic episodes (median duration, 22 days; range, 7-113 days) in 95 patients, 30 proven or probable IFIs (13 aspergillosis, 15 candidiasis, and 2 mixed IFIs) were diagnosed. Sensitivity, specificity, positive predictive value, negative predictive value, and efficiency of 2 consecutive BG values > or =7 pg/mL for diagnosis of proven or probable IFI was 0.63 (95% confidence interval, 0.44-0.79), 0.96 (95% confidence interval, 0.89-0.98), 0.79 (95% confidence interval, 0.57-0.92), 0.91 (95% confidence interval, 0.84-0.95), and 0.89, respectively. The time interval between onset of fever as first sign of IFI and BG antigenemia was significantly shorter than the time to diagnosis of IFI by clinical, microbiological, radiological, and/or histopathological criteria (P < .001). BG values >50 pg/mL were observed in only 2 patients, both of whom experienced failure of antifungal therapy. CONCLUSION: Monitoring of BG antigenemia is a useful noninvasive method for early diagnosis of IFI in patients with acute leukemia.     

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。     

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.