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。     

侵袭性真菌感染分子病理诊断进展

组织病理学是诊断侵袭性真菌感染的金标准之一,但由于病原真菌在组织学中形态的相似性以及混合感染的存在,难以将病原真菌鉴定到属或种水平。分子病理诊断方法如聚合酶链式反应(PCR)、基于激光捕获显微切割的LCM-PCR及荧光原位杂交(FISH)对福尔马林固定石蜡包埋(FFPE)组织中病原真菌具有高效、快速、高特异性的诊断价值。该文主要针对分子病理技术在侵袭性真菌感染领域的研究进展进行综述。     

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。     

抗真菌感染新药研究进展

随着免疫功能缺陷人群的增多,侵袭性真菌感染（invasive fungal infections,IFIs）的发病率和死亡率逐年上升,严重威胁人类健康。目前临床常用抗侵袭性真菌感染药物有三唑类（氟康唑）、多烯类（两性霉素B）、棘白菌素类（卡泊芬净）等,然而这些药物并不能满足临床需要,侵袭性真菌感染的死亡率仍居高不下。因此,本文着重于目前处于临床研究阶段的抗真菌感染新药,根据作用靶点不同依次介绍：作用于细胞壁的新型葡聚糖合成酶抑制剂CD101和SCY-078、几丁质合成酶抑制剂尼可霉素Z、GPI锚定蛋白抑制剂APX001;作用于细胞膜的CYP51抑制剂VT-1161和VT-1129、破坏细胞膜通透性药物CAmB;影响细胞代谢的嘧啶合成抑制剂F901318,以及生物制剂包括细胞表面凝集素样序列3蛋白疫苗（NDV-3）和抗真菌感染抗体Mycograb。本文主要综述了上述新药的研究进展,包括作用机制、体内外活性、临床研究结果等,为相关药物的研发与未来的临床应用提供参考。     

侵袭性真菌感染的流行病学和诊断研究进展

伴随着侵袭性真菌感染(Invasive fungal infection,IFI)的迅猛增长,逐渐认识到对许多真菌诊断的重要性,本文就侵袭性真菌感染的流行概况、危险因素以及传统和新近发展的诊断方法作一综述。     

血浆(1-3)-β-D葡聚糖对院内侵袭性真菌感染诊断的临床价值

目的探讨血浆(1-3)-β-D葡聚糖(即G实验)对院内侵袭性真菌感染的临床价值。方法选择2016.11~2017.4在宁夏医科大学总医院住院患者中院内侵袭性真菌感染的高危患者132例,血浆(1-3)-β-D葡聚糖含量使用MB-80微生物快速检测动态系统及其试剂进行检测,用ROC曲线比较G实验、真菌培养、G实验联合真菌培养的检测结果。结果 132例高危院内IFI感染的患者中,共有43例诊断为院内侵袭性真菌感染,真菌培养的敏感度为67%,特异度为96%,阳性预测值(PPV)和阴性预测值(NPV)分别是0.72和0.80,G实验的敏感度为70%,特异度为88%,PPV和NPV分别是0.73和0.86;G实验真菌培养检测的敏感度提高为84%,特异度提高为92%,阳性预测值0.78,阴性预测值0.92;G实验Youden指数0.58,真菌培养Youden指数0.63,联合检测Youden指数提高到0.76;G实验结果、真菌培养结果及联合检测结果进行ROC曲线分析,曲线下面积分别为0.717,0.757及0.798。结论 G实验是一种快速、简便、实用的侵袭性真菌感染的早期诊断方法,联合传统真菌培养可提高诊断的敏感度、特异度及诊断价值。     

CRISPR-Cas9基因编辑技术在念珠菌中的应用研究进展

正近年来,真菌感染已经成为严重威胁全球健康的疾病,全球约有3亿人遭受了侵袭性真菌感染,造成每年约有160万人死亡,接近结核病的死亡人数~([1])。尤其随着免疫功能低下人群的不断增加,侵袭性真菌感染导致的死亡率高达30%～90%~([2])。念珠菌属是真菌感染的主要致病菌,白念珠菌仍然是最常见的菌种,而非白念珠菌侵袭性感染所占的比例明显升高~([3-4])。目前,念珠菌对抗真菌药物的耐药问题面临严峻的挑战,     

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,     

临床侵袭性真菌病实验室诊断学术研讨会征文通知

当前侵袭性真菌感染在临床上的危害日益增大,其诊断和治疗存在严峻挑战,由中华医学会检验分会临床微生物学组主办,卫生部主管《医学参考报》检验医学频道和北京协和医院检验科临床微生物专业组联合承办的此次会议将邀请国内外知名临床侵袭性真菌病学专家就临床侵袭性真菌病实验室诊断技术进行深入研讨。会议将围绕以下重点议题展开：（1）临床常见侵袭性真菌的分离培养及形态学鉴定技术。（2）分子生物学诊断技术研究进展。（3）侵袭性真菌体外药敏试验方法。（4）侵袭性真菌耐药监测及耐药机制的研究。     

探寻人类病原真菌——一项漫长的研究之旅

<正>随着临床上各种原因导致的免疫受损宿主不断增多,真菌感染尤其是条件致病性真菌所引起的侵袭性真菌感染日益增多,且具有诊断耗时、疗效差、治疗费用高等特点,已成为严重影响人类生活质量、威胁生命健康的全球共同关注的重要健康问题。据悉,全世界每年由真菌引起的致命性侵袭性真菌感染超过250万例,单在美国,每年有超过160万人死于严重真菌感染,花费超过7亿美金。近年来出现的     

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.     

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.     

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。     

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.     

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.     

侵袭性真菌感染治疗新进展

随着免疫受损人群的增多,近年来侵袭性真菌感染的发生率逐渐升高,由此导致的致病率也逐年上升.如何及时诊断并有效的治疗侵袭性真菌感染已成为临床上面临的挑战之一.该文就侵袭性真菌感染的流行病学、病因学及现有的治疗策略等方面进行综述.     

Invasive Fungal Infections: A Continuing Challenge Report from the 17th International Symposium on Infections in the Immunocompromised Host, Genoa, Italy, 24–27 July 2012

The management of invasive fungal infections (IFIs) remains a challenge to the most experienced clinicians and mycologists as the therapeutic landscape continues to change. Delegates to the 17th International Symposium on Infections in the Immunocompromised Host heard that fungal epidemiology, patient demographics, diagnosis and treatment are all evolving. Diagnosis-driven therapy—pre-emptive or targeted—is the ideal approach to managing IFIs, but is dependent on reliable biomarker assays to identify, or at least strongly suggest, the organism(s) responsible. Biomarkers, however, are subject to ongoing research and so are also evolving. Some assays also may not be available in a particular centre. The same applies to investigations such as CT-scans and bronchoscopy that need to be performed in a timely fashion to help confirm an IFI. Thus, for patients with febrile neutropenia despite broad-spectrum antibiotic cover, clinicians without the appropriate diagnostic facilities prefer to start antifungal (AF) treatment immediately whilst attempting to confirm the diagnosis. Empirical therapy therefore looks likely to have a role for some time. For high-risk patients, such as those with haematological malignancies and/or undergoing haematopoietic stem cell transplantation (HSCT), the preferred strategy is to prevent IFIs using AF prophylaxis although regular screening with biomarkers is an alternative.