侵袭性真菌感染的分子诊断现状

近年来陧袭性真菌感染的发病率不断升高,侵袭性真菌感染的早期、准确诊断对于合理选用抗真菌药物,提高抗真菌疗效至关重要：另外,及时诊断侵袭性真菌感染可以减少经验性抗真菌治疗,降低抗真菌药物的选择性压力,     

艾滋病合并侵袭性肺真菌病的诊治

近年来,侵袭性真菌感染的发病率不断增加,其中肺真菌感染居首位,己成为免疫功能下降或缺陷宿主常见的死亡原因。艾滋病是经典免疫功能缺陷性疾病,合并真菌感染时需及时识别、治疗,以降低其病死率。国内、外各种有关侵袭性真菌感染诊治指南的不断问世,极大地提高了临床医生对侵袭性真菌病的认识和诊治水平。该文就艾滋病常见侵袭性肺真菌病:肺念珠菌病、肺孢子菌肺炎、肺马内菲青霉病、肺隐球菌病、肺曲霉病的诊断及治疗进展进行综述。     

分子生物学技术在侵袭性真菌感染诊疗中的应用进展

侵袭性真菌感染近年来呈上升趋势,临床分离真菌的构成比有所变化,耐药菌株的增加亦给临床的诊断、治疗和预防带来一定困难。因此,建立快速、准确的分子生物学鉴定方法,对侵袭性真菌感染的早期诊断有着重要意义。该文就分子生物学技术在侵袭性真菌感染早期诊疗中的应用研究作一综述。     

国产伏立康唑治疗侵袭性真菌感染6例临床观察

目的观察国产伏立康唑治疗恶性血液病患者侵袭性真菌感染（IFI）的临床疗效和安全性。方法以国产伏立康唑治疗6例发生于恶性血液病患者的侵袭性真菌感染,观察疗效及不良反应。结果6例患者中,有效4例,其中完全反应3例,部分反应1例。1例用药第6天出现低钾血症。结论国产伏立康唑是治疗恶性血液病患者侵袭性真菌感染的安全有效的药物,     

重症呼吸道病毒感染并发/继发侵袭性真菌感染

呼吸道病毒感染是侵袭性真菌感染的独立危险因素,包括流感、SARS-CoV、MERS-CoV等冠状病毒感染在内的重症病毒感染,因其发病机制或者治疗导致的免疫功能异常而继发侵袭性真菌感染的发病率及病死率已引起临床关注。特别是近来在全球范围内爆发的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)导致的新型冠状病毒感染(COVID-19),并发/继发侵袭性真菌感染的报道日益增多。了解重症病毒感染继发侵袭性真菌感染的危险因素、免疫反应、发病机制、临床表现及诊断治疗现状,有助于选择最适的诊断和治疗方法,从而做出及时诊断和精准治疗,以显著改善患者预后,降低患者病死率。     

两性霉素B治疗侵袭性肺部真菌感染的临床分析

目的 分析两性霉素B治疗ICU内侵袭性真菌感染的疗效与不良反应.方法 回顾性分析98例合并侵袭性肺部真菌感染的重症患者接受两性霉素B微泵静脉给药的临床资料.结果 两性霉素B的临床有效率77.55％,真菌清除率75.51％.不良反应包括寒战发热（9.18％）、皮疹（4.08％）、静脉炎（1.02％）、恶心呕吐（6.12％）、低钾血症（16.32％）、肝损害（1.02％）和肾损害（4.08％）.结论 国产两性霉素B对于重症患者侵袭性真菌感染疗效确定,采用持续微泵静脉给药不良反应发生率低.     

首届免疫缺陷与真菌感染高峰论坛暨真菌实验室检测学习班征文通知

正近年侵袭性真菌感染呈持续增多趋势,尤其在HIV、肿瘤、器官移植、血液病、重症监护患者中侵袭性真菌感染的发病率和病死率不断升高,侵袭性真菌感染的早期诊断、合理用药是治疗疾病和抢救生命的关键。为贯彻落实国家卫生计生委、国家发展改革委等14部门联合印发的《遏制细菌耐药国家行动计划(2016-2020年)》,提高二级以上综合医院细菌真菌感染诊疗能力,促进抗菌药物合理应用,维护人民群     

米卡芬净治疗重症侵袭性真菌感染40例的临床分析

目的评价米卡芬净治疗重症侵袭性真菌感染患者的疗效和安全性。方法采用回顾性分析2007年12月~2009年6月大连医科大学附属二院ICU病房40例侵袭性真菌感染患者应用米卡芬净治疗的临床资料。结果40例患者中,痊愈10例(25%),显效18例(45%),总有效率为70%,真菌清除率为60.8%,不良反应少,所有患者均耐受治疗。结论米卡芬净治疗重症侵袭性真菌感染安全、有效。     

肺部真菌感染的药物选择及治疗策略

由于高危人群的不断增多,侵袭性真菌感染的患病率和病死率均呈显著上升趋势。近年来提出应根据患者危险因素高低的不同,采取相应的治疗策略,包括预防治疗、经验治疗、临床诊断治疗和确诊治疗。肺部是真菌最常受累的器官,所以本文拟从循证医学的角度,就目前在侵袭性真菌感染,尤其是在肺部真菌感染中的各种抗真菌药物选择及其治疗策略作一综述。     

伊曲康唑治疗肝衰竭合并侵袭性肺部真菌感染患者的疗效和安全性分析

目的 评价伊曲康唑治疗肝衰竭合并侵袭性肺部真菌感染患者的疗效和安全性.方法 回顾性分析伊曲康唑治疗肝衰竭合并侵袭性肺部真菌感染患者的有效性和安全性.治疗方法:静脉注射伊曲康唑0.2g静脉滴注q12h 1天或者2天后改为伊曲康唑0.2g静脉滴注qd,疗程2～4周.结果 共有16例患者符合入选标准和排除标准纳入本研究,男女比例为3∶1.其中4例由白色念珠菌感染所造成,4例为热带念珠菌感染,8例为曲霉感染.临床结果:4例肝衰竭合并白色念珠菌感染患者,其中3例治愈出院,1例死于肝衰竭.4例肝衰竭合并热带假丝酵母感染患者,其中2例治愈出院,1例死于肺部感染,1例死于肝衰竭.8例肝衰竭合并肺曲菌病感染患者中,5例感染控制,其中2例治愈出院,2例接受肝移植,1例死于肝衰竭.3例肺部感染加重,死于呼吸衰竭.结论 伊曲康唑治疗肝衰竭合并侵袭性肺部真菌感染安全有效,可以作为治疗肝衰竭合并侵袭性肺部真菌感染患者的选择.     

High Incidences of Invasive Fungal Infections in Acute Myeloid Leukemia Patients Receiving Induction Chemotherapy without Systemic Antifungal Prophylaxis: A Prospective Observational Study in Taiwan

Invasive fungal infections (IFIs) is an important complication for acute myeloid leukemia (AML) patients receiving induction chemotherapy. However, the epidemiological information is not clear in Southeastern Asia, an area of potential high incidences of IFIs. To clarify it, we enrolled 298 non-M3 adult AML patients receiving induction chemotherapy without systemic anti-fungal prophylaxis from Jan 2004 to Dec 2009, when we applied a prospective diagnostic and treatment algorithm for IFIs. Their demographic parameters, IFI characters, and treatment outcome were collected for analysis. The median age of these patients was 51 years. Standard induction chemotherapy was used for 246 (82.6%) patients, and 66.8% of patients achieved complete remission (CR) or partial remission. The incidence of all-category IFIs was 34.6% (5.7% proven IFIs, 5.0% probable IFIs and 23.8% possible IFIs). Candida tropicalis was the leading pathogen among yeast, and lower respiratory tract was the most common site for IFIs (75.4%, 80/106). Standard induction chemotherapy and failure to CR were identified as risk factors for IFIs. The presence of IFI in induction independently predicted worse survival (hazard ratio 1.536 (1.100–2.141), p value = 0.012). Even in those who survived from the initial IFI insults after 3 months, the presence of IFIs in induction still predicted a poor long-term survival. This study confirms high incidences of IFIs in Southeastern Asia, and illustrates potential risk factors; poor short-term and long-term outcomes are also demonstrated. This epidemiological information will provide useful perspectives for anti-fungal prophylaxis and treatment for AML patients during induction, so that best chances of cure and survival can be provided.     

慢性重型乙肝继发侵袭性真菌感染的研究

目的明确侵袭性真菌感染(invasive fungal infections,IFI)在慢性重型乙肝患者中发病情况及主要病因。方法依据IFI和乙肝诊断标准,筛选上海长征医院感染科慢性重症乙肝患者,60例IFI者为病例组,66例未发生IFI为对照组,进行回顾性分析。结果 IFI患病率47.62%,病死率40%。乙肝病毒DNA水平是最主要的危险因素,当DNA高于3.16×103copies/mL,IFI发病可能性增大。结论慢重肝患者IFI的患病率和病死率超出临床预期,降低DNA拷贝可延缓乙肝进展,在预防及治疗IFI中亦具积极意义。     

Invasive fungal infection in immunocompromised patients

At present, the concept of immunocompromised patient cannot be applied exclusively to the classic groups of cancer, HIV-infected or transplanted patients. The cytotoxic treatment of patients with much more common conditions such as asthma, inflammatory bowel disease or rheumatoid arthritis has produced an exponential increase in the universe of patients with different degrees of immunological commitment. The generalization of transplantation procedures, even in advanced ages of life, the prolonged survival of patients with cancer and the decrease of the viral load in HIV-infected patients have resulted in long-term immunosupresions. The prevalence of invasive fungal infections (IFIs) is increasing in immunocompromised patients but each group of immunocompromised patients present peculiarities that must be recognized to be addressed appropriately. Despite the recent advances in the diagnosis and treatment of IFIs, they still present unacceptable morbility and mortality rates. Although IFIs are commonly caused by Candida spp. or Aspergillus spp., a variety of fungi are emerging as agents of IFIs. These emerging fungi require an individualized basic and clinical study. The aim of this work is to review the IFIs caused by common and emerging fungi in the three more numerous groups of immunocompromised patients: HIV-infected patients, solid organ transplant recipients and cancer patients, especially those with hematological malignancies or hematopoietic stem-cell transplantation.     

侵袭性真菌感染早期诊断技术的研究进展

侵袭性真菌感染（invasive fungal infections,IFIs）是真菌入侵人体导致血流、各脏器或全身播散的严重感染,以念珠菌为主的酵母样真菌和曲霉为主的丝状真菌最常见。近年来IFIs发病率及死亡率在全球范围内有显著上升趋势,严重威胁着人类的健康。早期快速的诊断方法现己成为真菌感染研究领域的热点和难点,对于患者及时治疗和死亡率的降低有十分重要的意义。本文旨对目前侵袭性真菌早期相关诊断技术以及临床研究的问题和现状予以总结,同时预测该领域未来的发展趋势。     

The role of adjuvant agents in treating fungal diseases

Invasive fungal infections (IFIs) remain a significant cause of morbidity and mortality despite the recent introduction of new antifungal medications. In this review, the available data on the use of adjuvant agents for the treatment of IFIs are discussed. Cytokines such as interferon-γ, colony-stimulating factors, granulocyte transfusions, and the monoclonal antibody efungumab may have in a role in the management of IFIs through augmentation of the host immune response, whereas pathogen-specific vaccines may help prevent infection. Pentraxin 3, an acute phase protein, may assist in the prevention and treatment of aspergillosis. Deferasirox, an iron chelator, is being investigated as an adjunctive therapy for the treatment of zygomycosis. Lactoferrin, an ironbinding protein, appears to have activity in Candida and Aspergillus infections, and omiganan may help prevent fungal catheter-related infections. Although none of these agents are currently approved for the treatment of IFIs, they may be involved in current and/or future treatment options when used in combination with antifungal drugs.     

Current Approaches in Antifungal Prophylaxis in High Risk Hematologic Malignancy and Hematopoietic Stem Cell Transplant Patients

Invasive fungal infections (IFIs) pose the most serious infectious risk to patients with hematologic malignancies and in those undergoing hematopoietic stem cell transplantation (HSCT). Invasive candidiasis has an incidence of 8–18% and a mortality of 30–40% in various reports. Invasive aspergillosis has an incidence of 4–15% and an even higher mortality of 60–85% cited in the published literature. IFIs have remained difficult to diagnose in a timely way in neutropenic and immunocompromised patients. A timely diagnosis is essential in promptly initiating antifungal therapy in order to optimize clinical outcomes. Thus, antifungal prophylaxis has an enormous appeal to minimize the threat from IFIs. In this article, the epidemiology and risk factors for IFIs as well as evidence from antifungal prophylaxis clinical trials in certain patient groups with hematologic malignancies are reviewed. Antifungal prophylaxis has been shown to be effective in certain settings. However, concerns about shifts in fungal epidemiology, emergence of resistance, drug toxicities, and drug interactions must be considered in deciding how and in whom to use antifungal prophylaxis.     

Is There Still a Place for Conventional Amphotericin B in the Treatment of Neonatal Fungal Infections?

Neonatal invasive fungal infections (IFIs) remain an increasing problem associated with high rates of morbidity and mortality, as well as late-onset neurodevelopmental implications. Invasive candidiasis remains the leading neonatal IFI. Candida albicans is the fungal species most often affecting this population, although a changing epidemiologic incidence to non-albicans Candida species is reported in some neonatal intensive care units. Many treatment recommendations are extrapolated from adult populations, emphasizing the need to establish the optimal antifungal agent, dosage, and duration of therapy in neonates. Historically, conventional amphotericin B has been considered an efficient and safe treatment approach for most neonatal IFIs. More recently, lipid formulations of amphotericin B have been studied, used alone or in combination with other antifungal agents such as azoles or echinocandins. The aim of this article is to review the published experience in the use of amphotericin B formulations to treat neonatal IFIs.     

米卡芬净预防血液系统恶性肿瘤患者侵袭性真菌感染有效性和安全性的Meta分析

目的系统评价米卡芬净预防血液系统恶性肿瘤患者侵袭性真菌感染(IFIs)的有效性及安全性,为临床治疗提供循证参考。方法计算机检索PubMed、Embase、Cochrane图书馆、中国知网(CNKI)、万方数据,检索时限为建库起至2021年1月,收集米卡芬净(试验组)对比常规抗真菌药物(两性霉素B及三唑类抗真菌药,对照组)的随机对照试验(RCT),对符合纳入标准的临床研究进行资料提取并采用Cochrane系统评价员手册5.0.2进行质量评价后,采用Rev Man 5.3统计软件对突破性IFIs、真菌感染死亡率、全因死亡率及因不良反应停药的发生率进行Meta分析。结果共纳入9项RCT,合计2 479例患者。Meta分析结果显示,试验组患者突破性IFIs发生率[OR=0.74,95%CI(0.50,1.07),P=0.11]、真菌感染死亡率[OR=0.73,95%CI(0.46,1.17),P=0.19]和全因死亡率[OR=0.94,95%CI(0.69,1.28),P=0.7]与对照组相比,差异无统计学意义;因不良反应停药的发生率[OR=0.46,95%CI(0.32,0.66),P<0.0001]显著低于对照组,差异有统计学意义。结论米卡芬净用于预防血液系统恶性肿瘤患者IFIs的效果与两性霉素B及三唑类抗真菌药物相当,且安全性更高。     

Genetic Susceptibility to Fungal Infections in Humans

Most fungal infections in humans occur in the setting of iatrogenic immunosuppression or HIV infection. In the absence of these factors, fungi cause mild, self-limited infections that typically involve mucocutaneous surfaces. Hence, when persistent or recurrent mucocutaneous infections (chronic mucocutaneous candidiasis [CMC]) or invasive fungal infections (IFIs) develop in a “normal” host, they are indicative of genetic defects causing innate or adaptive immune dysfunction. In this review, recent developments concerning genetic and immunologic factors that affect the risk for IFIs and CMC are critically discussed.     

Combination Therapy for Invasive Fungal Infections

The purpose of this review is to summarize and evaluate relevant literature on combination antifungal therapy for invasive fungal infections (IFIs). Cryptococcal meningitis has the largest body and highest quality in support of combination therapy with amphotericin B and flucytosine. More recent data in treatment of invasive aspergillosis suggest combination therapy with voriconazole and echinocandins may be effective in select patients. Quality studies are needed to define combination therapy in rare mold infections. Multiple strategies have been employed to optimize treatment of the growing incidence of IFIs. With exceptions as noted above, justification for the use of combination antifungal therapy is most often based on uncontrolled and/or underpowered studies, in vitro data, and case reports.