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肺部真菌感染的影像学特征
肺部真菌感染的影像学特征
肺部真菌感染是一种通过真菌感染引起的肺部疾病。
它的影像
学特征可以通过X射线、CT扫描等医学影像技术进行观察和诊断。
X射线检查
肺部真菌感染在X射线检查中的表现可以有以下特征：
1. 单个或多个肺部结节：真菌感染可引起肺部结节的形成，结
节一般呈圆形或卵圆形。
2. 肺实变阴影：部分真菌感染会导致肺组织炎症和肺实变，从
而在X射线上表现为浓密的阴影。
3. 支气管扩张：某些真菌感染可引起支气管扩张，从而在X射
线上显示为扩张的支气管影。
CT扫描
CT扫描是检测肺部真菌感染的最常用的方法之一，其特征包括：
1. 结节和肿块：真菌感染导致的结节和肿块能够在CT图像上
清晰可见，表现为圆形或不规则形状的结构。
2. 磨玻璃样密度影：磨玻璃样密度影是真菌感染的一个常见特征，表现为肺部区域密度增加，但仍能识别肺纹理。
3. 空洞和空腔：肺部真菌感染可能导致肺组织部分坏死和溶解，形成空洞和空腔。
4. 心包积液和胸水：某些真菌感染可以导致心包积液和胸水的
形成，在CT图像上可见。
肺部真菌感染的影像学特征可以通过X射线和CT扫描进行观察
和诊断。
常见的特征包括肺部结节，肺实变阴影，支气管扩张以及
CT图像中的结节、磨玻璃样密度影，空洞和空腔以及心包积液和胸水。
这些特征有助于医生进行肺部真菌感染的准确诊断和治疗。
肺部真菌感染的临床分析肺部真菌感染是一种常见的疾病，其临床表现多样，严重者可导致重大健康问题。
本文将对肺部真菌感染的临床表现、诊断和治疗进行分析，以便为临床医生提供参考。
一、临床表现肺部真菌感染的临床表现因感染菌种和患者免疫状况而异。
常见症状包括：咳嗽、咳痰、呼吸困难、胸痛、发热等。
即使没有明显的症状，也可能通过影像学检查发现肺部异常阴影。
特定的真菌感染如曲霉病常伴有肺外表现，如鼻窦炎、眼部炎症等。
二、诊断方法1. 呼吸道标本检测临床医生可以通过咳嗽咳痰样本、支气管肺泡灌洗液或支气管肺活检等方式获取呼吸道标本，并通过镜检、培养和分子生物学方法进行真菌检测。
这些方法可以确定感染的菌种和其对抗真菌药物的敏感性，有助于指导精准治疗。
2. 影像学检查肺部真菌感染常常在胸部X线、CT或MRI等影像学检查中呈现为斑点状、结节状或片状阴影。
影像学检查有助于评估病变范围和严重程度，并可作为监测治疗效果的指标。
3. 免疫学方法如果怀疑肺部真菌感染与免疫功能异常相关，可进一步进行免疫学检测。
例如，测定血清加曲霉素抗原和抗体水平，以及CD4+T细胞计数等指标，有助于评估患者免疫功能状态。
三、治疗原则1. 抗真菌药物治疗对于肺部真菌感染，抗真菌药物是主要的治疗手段。
根据真菌菌株的敏感性试验结果，可选择靶向治疗的药物，如三唑类药物（如伊曲康唑、氟康唑）、聚酮类药物（如阿莫西林果糖、氟胞嘧啶）等。
药物剂量和疗程的选择应根据患者的临床表现、感染的严重程度和免疫功能等进行调整。
2. 支持性治疗肺部真菌感染患者常常伴有胸闷、咳嗽等症状，可根据具体情况进行支持性治疗。
包括给予含氧、咳嗽止咳药物、解痰药物等，以改善症状和促进康复。
3. 增强免疫功能对于免疫功能受损的患者，应积极寻找病因并进行相应的治疗，以提高机体的免疫功能。
例如，针对HIV感染者应规范抗逆转录病毒治疗，减轻病毒复制对免疫系统的压力。
四、预防措施1. 加强个人卫生肺部真菌感染多与病原体通过呼吸道进入人体有关，因此加强个人卫生尤为重要。
侵袭性肺部真菌感染：临床诊断与治疗经验一、临床诊断诊断侵袭性肺部真菌感染，要掌握患者的详细病史，包括基础疾病、近期用药史、手术史、创伤史以及是否有吸入性感染源等。
这些信息对于诊断具有重要意义。
在询问病史的过程中，要特别关注患者是否有肺部基础疾病，如慢性阻塞性肺疾病、肺结核等。
影像学检查是诊断侵袭性肺部真菌感染的重要手段。
胸部X线、CT检查可以帮助发现肺部实变、空洞、坏死性肺炎等典型影像学表现。
然而，影像学检查并非确诊手段，需结合临床表现和其他检查结果综合判断。
实验室检查也可提供一定的诊断线索。
血常规、炎症标志物、真菌抗体等检查有助于判断感染的存在。
必要时，可行血培养、痰培养等检查，以寻找真菌病原体。
组织病理学检查是确诊侵袭性肺部真菌感染的金标准。
对于疑似肺部真菌感染的患者，可进行支气管镜检查或经皮穿刺活检，获取肺部组织进行病理学检查。
若在镜下发现真菌菌丝或孢子，可确诊为侵袭性肺部真菌感染。
二、治疗经验1. 抗真菌治疗：抗真菌药物是治疗侵袭性肺部真菌感染的关键。
根据真菌病原体种类及药物敏感试验结果，选择合适的抗真菌药物。
常见抗真菌药物包括氟康唑、伊曲康唑、伏立康唑等。
需要注意的是，抗真菌药物的使用应遵循剂量个体化原则，以确保疗效并减少不良反应。
2. 支持治疗：侵袭性肺部真菌感染的患者往往病情严重，需给予充分的支持治疗。
包括维持水电解质平衡、纠正贫血、改善营养状况等。
还需注意维持患者呼吸功能，对于严重呼吸困难的患者，可给予氧疗、无创或有创机械通气等治疗。
3. 去除感染源：侵袭性肺部真菌感染的患者往往存在基础疾病，如糖尿病、免疫抑制等。
因此，在治疗过程中，需积极控制感染源，去除诱发真菌感染的基础因素。
4. 预防性抗真菌治疗：对于高风险患者，如骨髓移植、重症患者等，可考虑预防性抗真菌治疗。
但需注意，预防性抗真菌治疗可能增加真菌耐药的风险，需权衡利弊后作出决策。
5. 个体化治疗：侵袭性肺部真菌感染的治疗需根据患者年龄、基础疾病、药物过敏史等因素进行个体化治疗。
肺部感染鉴别诊断肺部感染（Pulmonary Infection）是指引起肺组织炎症的感染性疾病，常见的包括肺炎（Pneumonia）、肺结核（Tuberculosis）和肺真菌感染（Fungal Infection）等。
准确鉴别和诊断肺部感染对于有效治疗和预防疾病的发展非常重要。
本文将介绍常见肺部感染的鉴别诊断方法，帮助读者更好地了解和诊断这些疾病。
一、肺炎的鉴别诊断肺炎是由细菌、病毒或其他病原体引起的肺组织感染，可分为社区获得性肺炎（Community-acquired Pneumonia, CAP）和医院获得性肺炎（Hospital-acquired Pneumonia, HAP）两种。
在鉴别诊断肺炎时，需要根据患者的临床表现、影像学结果和实验室检查等综合判断，具体方法如下：1. 临床表现评估根据患者的体温、咳嗽、咳痰、胸痛、呼吸困难等临床症状，结合血常规、炎性标志物等实验室检查，判断是否存在肺炎的可能性。
高热、咳嗽、咳痰和体征的阳性发现，对于肺炎的鉴别诊断非常重要。
2. 影像学评估常用的肺炎影像学检查包括胸部X线和胸部CT，目的是观察肺部有无浸润灶、小叶间隔增厚、空洞形成等特征。
肺炎的影像学表现有助于鉴别肺炎的类型，如细菌性肺炎常见的为片状浸润灶，而病毒性肺炎则主要表现为间质性改变。
3. 微生物学检查通过病原学检测可确定肺炎的病因，如血培养、呼吸道标本培养、痰涂片和支原体、冷球蛋白等病原学检测方法。
这些检测方法可以帮助找到导致肺炎的具体病原体，从而指导治疗和预防的选择。
二、肺结核的鉴别诊断肺结核是由结核分枝杆菌引起的慢性传染病，其鉴别诊断主要依据患者的病史、临床表现、实验室检查和影像学结果等来进行判断。
1. 病史评估询问患者的既往接触史、结核病史、症状出现的时间和持续时间等，有助于判断是否存在结核的可能性。
同时，需要了解患者的免疫状况、合并疾病等情况，为鉴别诊断提供更多的信息。
2. 临床表现评估肺结核的临床表现常见的有慢性咳嗽、咳痰、盗汗、低热、乏力等。
肺真菌病诊断和治疗专家共识肺真菌病诊断和治疗专家共识一、名词和术语肺真菌病：由真菌引起的肺部疾病，主要指肺和支气管的真菌性炎症或相关病变，广义地讲可以包括胸膜和纵膈。
侵袭性真菌病：指真菌直接侵犯肺或支气管引起的急、慢性组织病理损害所导致的疾病。
播散性肺真菌病：指侵袭性肺真菌病扩散和累及肺外器官，或发生真菌血症。
深部真菌感染：指真菌侵入内脏、血液、黏膜或表皮角质层以下深部皮肤结构引起的感染。
二、真菌分类主要致病性下呼吸道真菌种类有：酶母菌，霉菌，双相型真菌，类真菌四类。
按照致病性又分为致病性与条件致病性真菌。
三、肺真菌的诊断1诊断依据：危险因素：⑴外周血WB C＜0.5×109/L，中性粒细胞减少或缺乏，持续10d；体温＞38℃或＜36℃，并伴有下列情况之一：①此前60d 内出现持续的中性粒细胞减少（≥10d）；②此前30d内曾接受或正在接受免疫抑制剂治疗；③有侵袭性真菌感染史；④AIDS患者；⑤存在于移植物抗宿主病；⑥持续应用糖皮质激素3周以上；⑦有慢性基础疾病；⑧外伤、大手术、长期住ICU、长时间机械通气、体内留置导管、全胃肠外营养和长期使用广谱抗生素（任一项）侵袭性肺真菌病的临床特征：⑴主要临床特征：①侵袭性肺曲霉病；②肺孢子菌肺炎。
⑵次要临床特征：①持续发热>96h，经积极的抗生素治疗无效；②具有肺部感染症状及体征；③影像学检查可见除主要临床特征之外的，新的非特异性肺部浸润影。
微生物检查：⑴气管内吸引物或合格痰标本直接镜检发现菌丝，且培养连续≥2次分离到同种真菌；⑵支气管肺泡灌洗液经直接镜检发现菌丝，真菌培养阳性；⑶合格痰液或支气管肺泡灌洗液直接镜检或培养发现新生隐球菌；⑷乳胶凝集法检测隐球菌荚膜多糖抗原呈阳性结果；⑸血清1,3-β-D-葡聚糖抗原检测（G试验）连续2次阳性；⑹血清半乳甘露聚糖抗原检测（GM 试验）连续2次阳性。
1。
肺部真菌诊断标准-概述说明以及解释1.引言1.1 概述肺部真菌感染是一种严重的呼吸系统疾病，其发生率近年来呈逐渐增加的趋势。
随着免疫功能低下患者的增加，肺部真菌感染已成为临床上常见的致命疾病之一。
肺部真菌感染的特点是病情进展迅速且不易识别，常常导致严重的并发症和死亡。
然而，由于它的症状和体征往往与其他呼吸系统疾病相似，导致肺部真菌感染的诊断困难。
目前，肺部真菌感染的确诊主要依赖于临床表现、免疫学检测和影像学等方法。
然而，这些方法存在着一定的局限性和不足之处，需要进一步寻求更准确、快速、可靠的诊断手段。
本文将对现有的肺部真菌诊断方法进行综述，重点探讨各种方法的优缺点及其在临床上的应用。
通过系统地整理和评估已有的研究成果，我们希望能够找到一套全面有效的肺部真菌诊断标准，为临床治疗提供更科学的依据。
本文的研究目的是为了提高对肺部真菌感染的早期诊断率和准确性，从而及时采取有效的治疗措施，减少并发症的发生，降低病死率。
通过本文的研究，我们希望能够为肺部真菌感染的诊断和治疗提供指导，为临床医生提供更准确、可靠的诊断依据，为患者的健康和生命安全保驾护航。
1.2 文章结构文章结构本文的主要目的是深入探讨肺部真菌感染的诊断标准，为临床医生提供参考。
文章分为引言、正文和结论三个部分。
引言部分主要对肺部真菌感染进行概述，介绍其在临床中的重要性和存在的问题。
随后，文章会简要介绍本文的结构和目的，以便读者更好地理解和阅读本文。
正文部分将对肺部真菌感染的背景进行详细介绍。
在2.1节中，我们将探讨肺部真菌感染的定义、病因、发病机制以及其在临床上的表现。
理解这些背景知识对于准确诊断肺部真菌感染至关重要。
接下来，在2.2节中，我们将介绍现有的肺部真菌诊断方法。
这包括实验室检测、影像学检查以及其他临床评估方法。
我们将详细探讨每种方法的优缺点，以及其在肺部真菌感染诊断中的应用。
最后，在结论部分，我们将总结肺部真菌诊断的关键要点。
我们将回顾本文中介绍的各种方法，强调其在实际应用中的重要性。
肺部真菌感染的影像学特点肺部真菌感染的影像学特点X线检查肺部真菌感染在X线检查中的特点主要表现为以下几个方面：密度增高真菌感染引起的肺炎常常伴随着大量的炎性渗出物，这些渗出物在X线片上呈现高密度阴影。
这种密度增高可以是局限性的，也可以是弥漫性的。
结节病灶小的真菌感染病灶在X线片上通常呈现为结节状阴影，直径一般在1-2厘米。
这些结节病灶可以是单发的，也可以是多发的。
有时候，这些病灶之间还可能有空洞形成。
线形病灶真菌感染还可以引起肺组织内的小血管病灶，这些病灶在X线片上呈现为线形或细小的结节状阴影，称为线形病灶。
线形病灶通常是多发的，分布在肺野的各个部位。
CT扫描与X线相比，CT扫描可以提供更详细的肺部图像，并能够更准确地显示真菌感染的特点。
以下是CT扫描中常见的肺部真菌感染特点：模糊的边界真菌感染引起的肺炎通常呈现为模糊的边界，与周围正常肺组织相比较难以辨识。
这是因为感染部分的炎性渗出物和正常肺组织之间界限不清。
肺实变真菌感染引起的肺实变表现为肺组织密度增高，形成类似于肺实变的图像。
肺实变通常呈现为均匀的高密度阴影，可以是局限性的，也可以是弥漫性的。
穿透性病灶真菌感染引起的肺部病灶有时表现为穿透性病灶，即病灶穿透肺叶或肺段。
这种穿透性病灶通常呈现为空洞或空气-液平面。
淋巴结增大真菌感染还可以引起肺门或纵隔淋巴结的增大，这在CT扫描中表现为肺门或纵隔区域的结节样增大。
，肺部真菌感染在影像学上表现为密度增高、结节病灶、线形病灶等特点。
CT扫描能够提供更准确的图像，显示出真菌感染的更多细节。
对于怀疑肺部真菌感染的患者，及时进行影像学检查是非常重要的。
肺部真菌感染的影像学诊断
肺部真菌感染的影像学诊断
肺部真菌感染是一种常见的肺部疾病，其影像学诊断是确定诊
断的重要手段之一。
通过影像学检查，可以帮助医生确定患者是否
存在肺部真菌感染的病变，评估病变的范围和严重程度，从而指导
治疗方案的制定和疗效的监测。
常用的影像学检查方法包括X线胸片、CT扫描和MRI等。
其中，CT扫描是最常用的肺部真菌感染影像学诊断方法，具有较高的分辨率和敏感性。
根据肺部真菌感染的特点，影像学上可见以下表现：
1.单发或多发结节状阴影：肺部真菌感染常表现为肺内结节状
阴影，大小不一。
这些阴影可以是实性或半实性的，并可能出现空洞。
2.空洞形成：肺部真菌感染可导致肺组织的坏死和空洞形成。
这些空洞可能在肺部各个区域出现，并可能存在液平面。
3.支气管扩张：肺部真菌感染时，真菌通过支气管侵入肺组织，可导致支气管扩张的出现。
4.肺门淋巴结增大：在肺部真菌感染时，患者肺门淋巴结通常
会增大，并可能出现钙化。
除了以上常见的影像学表现，一些特殊的肺部真菌感染可能表现为肺段或肺叶的实性阴影，或以胸腔积液为主要表现。
，肺部真菌感染的影像学表现多样，具体表现受到患者免疫状态、真菌种类和病程等因素的影响。
在临床工作中，医生需要综合临床症状、实验室检查和影像学检查结果，来确定肺部真菌感染的具体诊断。
Changing face of health-care associated fungal infections Jacques Bille a,Oscar Marchetti b and Thierry Calandra bPurpose of reviewThe purpose of this review was to evaluate recent publications on the epidemiology,diagnosis and management of invasive fungal infections.RecentfindingsEpidemiological surveys have highlighted significant differences between Europe and the United States regarding the incidence and etiology of Candida bloodstream infections.Today,invasive aspergillosis is occurring in a much broader patient population than the classical immunocompromised hosts and includes mechanically ventilated intensive care unit patients and patients receiving corticosteroids for treatment of chronic lung diseases.Diagnosis is often delayed in these patients and prognosis is dismal.Measurement of galactomannan, mannan and antimannan antibodies,and b-(1–3)-D-glucan may help to speed up diagnosis.The epidemiology of invasive mold infections is changing.The frequency of non-fumigatus Aspergillus species is increasing,uncommon hyalo-or phaeo-hyphomycoses are emerging and breakthrough mold infections intrinsically resistant to azoles have been reported.Clinical trials have shown that new azoles and echinocandins are as efficacious as amphotericin B orfluconazole for the treatment of eosophageal or invasive candidiasis,for prophylaxis of invasive fungal infections in transplant patients,or for empirical antifungal therapy in patients with persistent fever and neutropenia.SummaryRecent data suggest that the epidemiology of invasive fungal infections may be changing with the emergence of uncommon molds and the occurrence of invasive aspergillosis in‘nonclassical’immunocompromised hosts. New diagnostic tools and improved antifungal agents are available to facilitate early diagnosis and offer new treatment options.Keywordsdiagnosis,epidemiology,fungi,infection,therapyCurr Opin Infect Dis18:314–319.ß2005Lippincott Williams&Wilkins.a Institute of Microbiology,Centre Hospitalier Universitaire Vaudois,CH-1011 Lausanne,Switzerland andb Infectious Diseases Service,Centre Hospitalier Universitaire Vaudois,CH-1011Lausanne,SwitzerlandCorrespondence to Prof.Jacques Bille,Institute of Microbiology,Centre Hospitalier Universitaire Vaudois,Rue du Bugnon48,CH-1011Lausanne,Switzerland Tel:+41213144057;fax:+41213144060;e-mail:jacques.bille@chuv.hospvd.chCurrent Opinion in Infectious Diseases2005,18:314–319AbbreviationsBSI bloodstream infectionHSCT hematopoietic stem cell transplantICU intensive care unitß2005Lippincott Williams&Wilkins0951-7375IntroductionFungi have emerged worldwide as an increasingly frequent cause of health-care associated infections [1,2].According to a recent epidemiological survey in the US[3],the incidence of fungal sepsis has increased threefold between1979and2000.Candida and Aspergillus are the most common causes of invasive fungal infections, accounting for70–90%and10–20%of all invasive mycoses,respectively.Five tofifteen percent of health-care associated infections are caused by Candida. Typically encountered in immunocompromised hosts, primarily in cancer and transplant patients,opportunistic fungal pathogens have also been recognized as a frequent cause of infections in debilitated surgical and critically ill patients.The purpose of this article is to review recent data on the epidemiology,diagnosis and management of invasive fungal infections(candidiasis,aspergillosis,and emerging fungi)with a special emphasis on uncommon hosts. Candida infectionsCandida spp.is still by large the leading cause of invasive fungal infections,particularly in the setting of surgical and intensive care unit(ICU)patients where new diagnostic tools could help to select at risk patients for preemptive therapy with safe and efficacious new drugs.EpidemiologyRecent epidemiological surveys conducted in the US have confirmed that candidemia is the fourth most com-mon cause of bloodstream infections(BSIs),representing 9.5%of all BSIs in a recent nationwide population sur-veillance study(Surveillance and Control of Pathogens of Epidemiological Importance–SCOPE),conducted in 50hospitals between1995and2002[4 ].In contrast, recent data from Europe have shown a less preeminent position for Candida spp.Candida spp.ranked number7 in a10-year study carried out in Switzerland,accounting for only2.9%of all BSIs[5 ].In another multinational European survey conducted in seven countries[6],314the rate of Candida BSIs was0.2–0.4per1000admis-sions compared with0.46per1000admissions in a US study.Another difference between studies conducted in the US and in Europe is the distribution of Candida spp.causing BSIs. C.albicans remained largely the predominant species in Europe,accounting for up to66%of all episodes of candidemia compared with approximately 55%in US studies.The frequency of C.glabrata BSIs was about14%in Europe,while it was19%in the US.An interesting parameter examined in the US population-based SCOPE study was the timing of Candida BSIs, which occurred at a median of22days after hospital admission compared with13and16days for bacteremias caused by Escherichia coli and Staphylococcus aureus, respectively.Therefore,this long delay,due to the fact that Candidafirst colonizes the patient before causing invasive infections,provides time for clinicians to initiate antifungal prophylaxis or preemptive therapy in high-risk patients.DiagnosisDiagnostic tools for early recognition of patients at risk of invasive fungal infections are needed to implement prophylactic or preemptive therapies.Several investi-gators have proposed clinical or biological criteria or scores to predict invasive candidiasis.One of these scores developed for ICU patients showed that the presence of one‘major’and two‘minor’risk criteria was present in about10%of patients who stayed in the ICU for more than3days,of whom10%went on to develop invasive candidiasis[7 ].Sensitive diagnostic markers would be helpful to identify patients who may benefit from preemptive therapy.Two recent studies have investi-gated this approach.Detection of mannan and/or anti-mannan antibodies in patients at risk of developing invasive candidiasis has been studied in neutropenic cancer patients.Among21patients with hepatosplenic lesions highly suggestive of candidiasis,18(86%)had positive mannan and/or antimannan tests at a median of 16days before radiological detection of liver or spleen lesions[8 ].Another surrogate marker of fungal infection is the detection of circulating b-(1–3)-D-glucan,which was found to be present in the serum of100%of leukemic patients with proven and probable invasive candidiasis, fusariosis or trichosporonosis at a median of10days before clinical diagnosis was made[9 ].TherapyThe results of several clinical trials have been published in2004.In addition to amphotericin B,fluconazole,and more recently caspofungin[10],new azoles and other echinocandins have been shown to be efficacious for the treatment of candidiasis.In randomized,double-blind studies,the efficacy of micafungin or anidulafungin was found to be comparable to that offluconazole for the treatment of esophageal candidiasis[11,12].In a randomized,open-label,comparative multicenter noninferiority trial of422patients with invasive Candida infections(of whom>95%had candidemia),voricona-zole(intravenously and then orally)was shown to be as effective as a regimen of intravenous amphotericin B(0.7–1.0mg/kg/day)followed by intravenous or oral fluconazole(!400mg/day).Success rates were40.7 versus40.7and65.5versus71.3for primary and second-ary analyses,respectively[13].A phase II dose-finding study of anidulafungin for the treatment of68patients with invasive candidiasis reported success rates in the range of84–90%[14 ].A small noncomparative trial on micafungin showed a100%response rate in patients with candidemia[15].A retrospective case–control analysis of491episodes of Candida BSIs in adult cancer patients showed that the administration of high-dose granulocyte transfusion was associated with improved survival,despite the presence of multiple predictors of increased mortality in patients receiving granulocytes [16].In HIV-positive patients,the incidence of candide-mia was reduced after highly active antiretroviral therapy, but its severity remained high with a crude60%mortality rate[17].MortalitySeveral studies have examined the outcome of Candida BSIs in special hosts.In premature infants,the mortality of candidemia reached20%among115neonates within 30days after positive blood culture[18 ]compared with 15%and6%for bacteremia due to Gram-negative and Gram-positive bacteria,respectively.In a case–control study of113patients with candidemia at a single institu-tion,the predictors of candidemia included Hickman catheters(odds ratio9.5),gastric acid suppressants (6.4),nasogastric tubes(3.7),and admission to ICU (6.4).The case fatality rate was40%.Surprisingly only15%of the patients received the recommended treatment regimens[19 ].In an accompanying editorial, Diekema and Pfaller[20 ]pointed to the devastating effects of Candida BSIs,the unchanged high mortality, and emphasized the paramount importance of preventive measures,such as improved hand hygiene,optimal catheter placement and care,prudent antibiotic use and potential benefits of empiric and prophylactic antifungal agents.Aspergillosis and emerging mold infections Despite the recent advent of new therapeutic options, such as voriconazole(the current treatment offirst choice)or caspofungin(for salvage therapy in refractory disease),invasive or disseminated aspergillosis remains a major threat for patients undergoing hematopoietic stem cell or solid organ transplantation.Health-care associated fungal infections Bille et al.315EpidemiologyDevelopment of invasive aspergillosis in nonclassical immunocompromised hosts,such as critically ill ICU patients,is more and more often reported[21].In a recent report aspergillosis developed in3.6%of1850 medical ICU patients and was associated with a mortality of80%[22 ].Several of these patients did not have classical risk factors,but various underlying conditions including liver cirrhosis,raising the question of the need for revisiting or enlarging the list of predisposing factors for aspergillosis in nonhemato-oncologic patients[22 ].In a Spanish active surveillance study of165non-ICU patients with health-care associated pneumonia[23], Aspergillus(12%)was the third most common cause of 60microbiologically documented cases of pneumonia, after S.pneumoniae(27%),and L.pneumophila(12%).Of the seven patients with pulmonary aspergillosis,only two were neutropenic,but four had received corticosteroids. Moreover,an outbreak of gastric mucormycosis occurring infive previously immunocompetent mechanically venti-lated ICU patients with severe pneumonia was attributed to contaminated wooden tongue depressors.All but one patient presented with severe gastrointestinal bleeding and the attributable mortality was40%[24].Not only is aspergillosis occurring in a much broader patient population,but a shift in the epidemiology of these infections has also been noticed,with an increasing frequency of Aspergillus infections other than A.fumigatus. In some institutions,A.terreus is almost as frequently involved as A.fumigatus[25].A.terreus is more often health-care associated,is more resistant to amphotericin B,and is associated with lower response rates(28%versus 39%)to antifungal therapy when compared with A. fumigatus.A very intriguing report has described the isolation at a single institution of seven isolates of a potentially new variant of A.fumigatus,characterized by multiresistance to old and new azoles,echinocandins,and for few of them to polyenes[26 ].Investigations did notfind an epidemio-logic link between these cases.A possible link has been suspected between the increas-ing use of voriconazole,because of its superior efficacy for the treatment of invasive aspergillosis,and breakthrough infections caused by mucorales,a family of opportunistic molds resistant to voriconazole.Within a year,four reports from different cancer centers described18cases of Mucor infections suggestive of an increased incidence (3.2–8.9%of all transplanted patients)in voriconazole-treated patients[27–30].The characteristics of most of these infections were a late occurrence and a dismal outcome.Additional cases of Absidia corymbifera infec-tions in lung transplant patients receiving voriconazole prophylaxis have been reported[31].In a thoughtful accompanying editorial[32 ],the advantages of new antifungal agents(increased survival of patients with invasive aspergillosis)are balanced against the potential risk of emergence of resistant fungi,with a call for a careful evaluation of the indications for voriconazole prophylaxis in immunocompromised hosts.Whether or not these epidemiological changes and increased resist-ance pattern of mold infections are the sole result of selective pressure exerted by the prophylactic or thera-peutic use of new antifungal agents or of other confound-ing cofactors is unclear at this stage.Indeed,these observations are reminiscent of similar debates as to the role offluconazole orfluoroquinolones in the occur-rence of C.krusei or viridans streptococcal infections in cancer patients respectively.Beyond Aspergillus and mucorales,many other species of filamentous fungi belonging to the hyalohyphomycoses (Fusarium spp.,Scedosporium spp.)or to the phaeohypho-mycoses(Bipolaris spp.,Exophiala spp.,Wangiella spp.) have attracted recent attention[33–35].Most of the emerging fungi are characterized by in-vitro resistance to one or more families of antifungal agents and a poor prognosis in immunocompromised patients.Given the increasing choice of antifungal drugs,it is important to be aware of the susceptibility pattern of these fungi[36 ] and of the results obtained in experimental animal models using either single-agent or combination antifun-gal therapy[37 ].Scedosporium spp.is one of the multi-resistant molds occasionally causing infections in hematopoietic stem cell transplant(HSCT)or solid organ transplant recipients.A multicenter study conducted in five transplant centers collected13cases and reviewed67 additional published cases[38 ].More than half of the infections were disseminated with a predominance of S. prolificans infections among HSCT patients.They were characterized by an early onset(1.3months after trans-plantation),occurred during neutropenia in67%of the cases and were associated with BSIs in a third of the cases. S.prolificans is usually resistant–at least in vitro–to all currently available antifungal agents.In solid organ trans-plant patients,the time between transplantation and Scedosporium infection was longer(4.2months)compared with HSCT e of voriconazole as primary therapy with adjunctive surgery was associated with improved survival,whereas disseminated infection was predictive of a poor survival(less than20%).DiagnosisDespite the availability of new diagnostic tests,such as serum galactomannan,a circulating cell-wall antigen of Aspergillus,the diagnosis of aspergillosis remains difficult and is all too often made late.The optimal threshold for galactomannan was examined prospectively in a series of 124episodes of neutropenia in cancer patients with high pretest probability for invasive aspergillosis[39 ].A316Nosocomial and hospital related infectionsdynamic threshold(defined as at least two sequential serum galactomannan tests with an optical density!0.5) had a specificity and positive predictive value of98.6%, allowing early diagnosis.Another study of galactomannan in67HSCT recipients confirmed that decreasing the index cut-off for positivity from 1.0to0.5increased sensitivity from54%to83%with minimal loss of speci-ficity[40 ].In patients without typical risk factors,asper-gillosis is notoriously difficult to diagnose premortem!A study of222autopsies of ICU patients revealed unex-pectedfindings in50of them,including nine cases of fungal infection and six(2.7%of all deaths)with disseminated aspergillosis(lungs,myocardium,kidneys). All six patients had received corticosteroids(infive cases for chronic obstructive pulmonary disease),and had been mechanically ventilated[41,42 ].TherapyAmphotericin B(deoxycholate or lipid formulations), itraconazole,voriconazole and caspofungin are treatment options for patients with invasive aspergillosis or persis-tent fever during neutropenia.Voriconazole has been recently shown to be superior to amphotericin B deoxy-cholate for the treatment of invasive aspergillosis and is now the treatment offirst choice[43].New data became available in2004.The efficacy and safety of caspofungin as salvage therapy for invasive aspergillosis was evaluated in83patients with hematological malignancies,allo-geneic blood and marrow transplantation or solid organ transplantation,who were refractory(86%)to,or intoler-ant(14%)of,conventional antifungal therapy[44 ].Com-plete and partial responses to caspofungin were observed in four(5%)and33(40%)of the83patients.Treatment was well tolerated with minimal drug-related toxicity (clinical12%,laboratory14%).A noncomparative study of micafungin conducted in Japan reported success rates between60%and67%in19patients with different types of invasive aspergillosis[15].In1095patients with persistent fever and neutropenia[45 ],empirical antifungal therapy with caspofungin was found to be as efficacious as(based on afive-component composite endpoint)and better tolerated than liposomal amphoter-icin B(overall success rates33.9%versus33.7%,95% confidence interval(CI)for the differenceÀ5.6–6.0%; nephrotoxicity 2.6%versus11.5%;infusion-related events35.1%versus51.6%,P<0.001).In a double-blind,multicenter,phase III study in882adult and pediatric patients undergoing HSCT[46 ],micafungin (50mg)was superior tofluconazole(400mg)for prophy-laxis of invasive fungal infections(overall efficacy80.0% versus73.5%,95%CI for the difference0.9–12.0%, P¼0.03).No relapse of invasive aspergillosis was reported in10patients receiving secondary prophylaxis with voriconazole during HSCT[47].Finally,a case–control study[48 ]reported improved survival in patients with invasive aspergillosis receiving salvage treatment for refractory infection with a combination of voriconazole and caspofungin(n¼16)when compared with voriconazole alone(n¼31;hazard ratio0.3,95%CI 0.1–0.8,P<0.05).ConclusionTwo recent changes in the epidemiology of invasive fungal infections are the emergence of uncommon molds, some resistant to antifungal drugs used as prophylactic agents,and the growing recognition of invasive aspergil-losis in the‘nonclassical’immunocompromised host.New diagnostic tools and improved antifungal agents will facilitate earlier diagnosis and offer new treatment options. AcknowledgementsThis work was supported by grants from the Swiss National Science Foundation(3100-066972.01),the Bristol-Myers Squibb Foundation and the Leenaards Foundation.TC is a recipient of a career award from the Leenaards Foundation.References and recommended readingPapers of particular interest,published within the annual period of review,have been highlighted as:of special interestof outstanding interest1Banerjee SN,Emori TG,Culver DH,et al.Secular trends in nosocomial primary bloodstream infections in the United States,1980–1989.National Nosocomial Infections Surveillance System.Am J Med1991;91:86S–89S. 2Beck-Sague´CM,Jarvis WR.National Nosocomial Infections Surveillance System.Secular trends in the epidemiology of nosocomial fungal infections in the United States,1980–1990.J Infect Dis1993;167:1247–1251.3Martin GS,Mannino DM,Eaton S,Moss M.The epidemiology of sepsis in the United States from1979through2000.N Engl J Med2003;348:1546–1554.4Wisplinghoff H,Bischoff T,Tallent SM,et al.Nosocomial bloodstream infections in US hospitals:analysis of24,179cases from a prospective nationwide surveillance study.Clin Infect Dis2004;39:309–317.In this large multicenter study of nosocomial bloodstream infections in US hospitals,only coagulase-negative staphylococci(31%),S.aureus(20%)and enterococci(9%)were more often recovered than Candida species(9%).5Marchetti O,Bille J,Fluckiger U,et al.Epidemiology of candidemia in Swiss tertiary care hospitals:secular trends,1991–2000.Clin Infect Dis2004;38:311–320.In this Swiss nationwide study,Candida species represented less than3%of all bloodstream isolates(and C.albicans two-thirds of them)without increase over time despite increasing consumption of azoles and high-risk activities.6Tortorano AM,Peman J,Bernhardt H,et al.Epidemiology of candidaemia in Europe:results of28-month European Confederation of Medical Mycology (ECMM)hospital-based surveillance study.Eur J Clin Microbiol Infect Dis 2004;23:317–322.7Ostrosky-Zeichner L.Prophylaxis and treatment of invasive candidiasis in the intensive care setting.Eur J Clin Microbiol Infect Dis2004;23:739–744.A nice review of possible strategies to prevent invasive candidiasis in ICU patients, with emphasis on how to target high-risk patients.8Prella M,Bille J,Pugnale M,et al.Early diagnosis of invasive candidiasis with mannan antigenemia and antimannan antibodies.Diag Microbiol Infect Dis 2005;51:95–101.Thefirst study showing the usefulness of mannan and antimannan serum level determination in patients with hepatosplenic candidiasis,allowing the diagnosis of this complication before neutrophil recovery in78%of patients.9Odabasi Z,Mattiuzzi G,Estey E,et al.b-D-Glucan as a diagnostic adjunct for invasive fungal infections:validation,cutoff development,and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome.Clin Infect Dis2004;39:199–205.All20acute myelogenous leukemia or myelodysplastic syndrome patients with proven or probable invasive fungal infections were positive for b-D-glucan whereas all patients without fungal infection were negative.10Mora-Duarte J,Betts R,Rotstein C,et parison of caspofungin and amphotericin B for invasive candidiasis.N Engl J Med2002;347:2020–2029.Health-care associated fungal infections Bille et al.31711de Wet N,Llanos-Cuentas A,Suleiman J,et al.A randomized,double-blind, parallel-group,dose–response study of micafungin compared withflucona-zole for the treatment of esophage candidiasis in HIV-positive patients.Clin Infect Dis2004;39:842–849.12Krause DS,Simjee AE,van Rensburg C,et al.A randomized,double-blind trial of anidulafungin versusfluconazole for the treatment of esophageal candi-diasis.Clin Infect Dis2004;39:770–775.13Kullberg BJ,Pappas P,Ruhnke M,et al.Voriconazole compared with a strategy of amphotericin B followed byfluconazole for treatment of candi-daemia in non-neutropenic patients.Clin Microbiol Infect2004;10(Suppl3):41.14 Krause DS,Reinhardt J,Vazquez JA,et al.Phase2,randomized,dose-ranging study evaluating the safety and efficacy of anidulafungin in invasive candidiasis and candidemia.Antimicrob Agents Chemother2004;48:2021–2024.Phase II dose-finding study of the efficacy and safety of anidulafungin for the treatment of invasive candidiasis.15Kohno S,Masaoka T,Yamaguchi H,et al.A multicenter,open-label clinical study of micafungin(FK463)in the treatment of deep-seated mycosis in Japan.Scand J Infect Dis2004;36:372–379.16Safdar A,Hanna HA,Boktour M,et al.Impact of high-dose granulocyte-transfusions in patients with cancer candidemia:retrospective case-control analysis of491episodes of Candida species bloodstream infections.Cancer 2004;101:2859–2865.17Bertagnolio S,de Gaetano Donati D,Tacconelli E,et al.Hospital-acquired candidemia in HIV-infected patients:incidence,risk factors and predictors of outcome.J Chemother2004;16:172–178.18 Benjamin DK,DeLong E,Cotten CM,et al.Mortality following blood culture in premature infants:increased with Gram-negative bacteremia and candidemia, but not Gram-positive bacteremia.J Perinatol2004;24:175–180.Multicenter cohort study of premature infants attributing the highest in hospital mortality(26%)due to bloodstream infections to patients with candidemia.19 Puzniak L,Teutsch S,Powderly W,Polish L.Has the epidemiology of nosocomial candidemia changed?Infect Control Hosp Epidemiol2004; 25:628–633.Matched case–control study showing little change in the epidemiology of candi-demia and the nonapplication of recent treatment guidelines for the treatment,in particular regarding duration of therapy.20 Diekema DJ,Pfaller MA.Nosocomial candidemia:an ounce of prevention is better than a pound of cure.Infect Control Hosp Epidemiol2004;25:624–626.Thoughtful editorial on areas of progresses(diagnosis,management)and those for which improvements would be welcome(in particular,the unchanged hospital acquisition of BSI).21Denning WD.Aspergillosis in‘non-immunocompromised’critically ill patients.Am J Respir Crit Care Med2004;170:580–581.22 Meersseman W,Vandecasteele SJ,Wilmer A,et al.Invasive aspergillosis in critically ill patients without malignancy.Am J Respir Crit Care Med2004; 170:621–625.Invasive aspergillosis is a devastating disease in ICU patients without malignancies. 23Sopena N,Sabria`M,Neunos2000Study Group.Multicenter study of hospital-acquired pneumonia in non-ICU patients.Chest2005;127:213–219.24Maravı´-Poma E,Rodrı´guez-Tudela JL,Garcı´a de Jalo´n J,et al.Outbreak of gastric mucormycosis associated with the use of wooden tongue depressors in critically ill patients.Intensive Care Med2004;30:724–728.25Hachem RY,Kontoyiannis DP,Boktour MR,et al.Aspergillus terreus:an emerging amphotericin B-resistant opportunistic mold in patients with hema-tologic malignancies.Cancer2004;101:1594–1600.26 Balajee SA,Weaver M,Imhof A,et al.As pergillus fumigatus variant with decreased susceptibility to multiple antifungals.Antimicrob Agents Chemother2004;48:1197–1203.A worrisome description of seven clinical isolates of a A.fumigatus white variant resistant to voriconazole and caspofungin,and differing at the mitochondrial cytochrome b gene sequence level.27Marty F,Cosimi L,Baden L.Breakthrough zygomycosis after voriconazole treatment in recipients of hematopoietic stem-cell transplants.New Engl J Med2004;350:950–952.28Siwek GT,Dodgson KJ,de Magalhaes-Silverman M,et al.Invasive zygomy-cosis in hematopoietic stem cell transplant recipients receiving voriconazole prophylaxis.Clin Infect Dis2004;39:584–587.29Imhof A,Balajee SA,Fredricks DN,et al.Breakthrough fungal infections in stem cell transplant recipients receiving voriconazole.Clin Infect Dis2004;39:743–746.30Vigouroux S,Morin O,Moreau P,et al.Zygomycosis after prolonged use of voriconazole in immunocompromised patients with hematologic disease: attention required.Clin Infect Dis2005;40:e35–e37.31Mattner F,Weissbrodt H,Strueber M.Two case reports:fatal Absidia corymbifera pulmonary tract infection in thefirst postoperative phase of a lung transplant patient receiving voriconazole prophylaxis,and transient bronchial Absidia corymbifera colonization in a lung transplant patient.Scand J Infect Dis2004;36:312–314.32Kauffman CA.Zygomycosis:reemergence of an old pathogen.Clin Infect Dis 2004;39:588–590.The prevention of aspergillosis,for which we now have effective antifungal drugs such as voriconazole,appears to select for other mold infections,for which we have little therapeutic option.33Walsh TJ,Gross A,Hiemenz J,et al.Infections due to emerging and uncommon medically important fungal pathogens.Clin Microbiol Infect 2004;10:48–60.34Revankar SG,Sutton DA,Rinaldi MG.Primary central nervous system phaeohyphomycosis:a review of101cases.Clin Infect Dis2004;38:206–216.35Nucchi M,Marr KA,Queiroz-Telles F,et al.Fusarium infection in hemato-poietic stem cell transplant recipients.Clin Infect Dis2004;38:1237–1242. 36Pfaller MA,Diekema DJ.Rare and emerging opportunistic fungal pathogens: concern for resistance beyond Candida albicans and Aspergillus fumigatus.J Clin Microbiol2004;42:4419–4431.An up-to-date and very useful review of susceptibility and resistance data to both new and established antifungal agents of selected emerging yeast andfilamentous fungi.37Johnson MD,MacDougall C,Ostrosky-Zeichner L,et bination anti-fungal therapy.Antimicrob Agents Chemother2004;48:693–715. Extremely thorough and critical review of in-vitro,animal and human studies of antifungal combination therapy.Very useful in providing a framework for future studies.38Husain S,Mun˜oz P,Forrest G,et al.Infections due to Scedosporium apiospermum and Scedosporium prolificans in transplant recipients:clinical characteristics and impact of antifungal agent therapy on outcome.Clin Infect Dis2005;40:89–99.This review of80cases of Scedosporium infections in transplant recipients nicely outlines the many differences(host,antifungal susceptibility,prognosis)of the two major species of Scedosporium,S.apiospermum and S.prolificans.39Maertens J,Theunissen K,Verbeken E,et al.Prospective clinical evaluation of lower cut-offs for galactomannan detection in adult neutropenic cancer patients and haematological stem cell transplant recipients.Br J Haematol 2004;126:852–860.The latest of a series of carefully designed studies assessing the role of galacto-mannan serum screening for the early diagnosis of invasive aspergillosis in BMT patients.40Marr KA,Balajee SA,McLaughlin L,et al.Detection of galactomannan antigenemia by enzyme immunoassay for the diagnosis of invasive aspergil-losis:variables that affect performance.J Infect Dis2004;190:641–649.A systematic evaluation of all variables affecting the sensitivity,specificity,and the predictive values of galactomannan serum levels for the diagnosis of invasive aspergillosis.41Dimopoulos G,Piagnerelli M,Berre´J,et al.Disseminated aspergillosis in intensive care unit patients:an autopsy study.J Chemother2003;15:71–75.42Dimopoulos G,Piagnerelli M,Berre´J,et al.Post-mortem examination in the intensive care unit:still useful?Intensive Care Med2004;30:2080–2085. Among2984ICU patients,there were489deaths;222autopsies were con-ducted revealing nine cases of unsuspected invasive fungal infections.43Herbrecht R,Denning DW,Patterson TF,et al.Voriconazole versus ampho-tericin B for primary therapy of invasive aspergillosis.N Engl J Med2002;347:408–415.44Maertens J,Raad I,Petrikkos G,et al.Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy.Clin Infect Dis2004;39:1563–1571. Most patients were refractory to classical antifungal agents.As many as50%of lung aspergillosis responded to caspofungin,compared with23%of cases of disseminated aspergillosis.45Walsh TJ,Teppler H,Donowith GR,et al.Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia.N Engl J Med2004;351:1391–1402. Randomized double-blind empirical treatment study comparing caspofungin (50mg/day)with liposomal amphotericin B(3mg/kg/day)with stratification according to risk and previous antifungal prophylaxis.46van Burik JAH,Ratanatharathorn V,Stepan DE,et al.Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutro-penia in patients undergoing hematopoietic stem cell transplantation.Clin Infect Dis2004;39:1407–1416.Randomized double-blind multi-institutional comparative phase III trial comparing micafungin50mg/day withfluconazole400mg/day.318Nosocomial and hospital related infections。
