侵袭性曲霉病兔模型的构建

目的构建侵袭性曲霉病动物模型。方法采用气管切开、气管内接种构建侵袭性曲霉病兔模型。结果烟曲霉侵袭性感染发生在接种1周内,而其生存期超过2周。结论成功构建了侵袭性曲霉病兔模型,它是研究侵袭性曲霉病的免疫学发病机制、评估新型抗真菌药物的疗效、发现烟曲霉的毒力因子以及评价新的诊断方法等较为理想的动物模型。     

肺曲霉病12例临床分析

肺曲霉病（pulmonary aspergillosis）由曲霉菌感染引起，临床上分为曲霉寄植（肺曲霉球），变应性支气管肺曲霉病，侵袭性肺曲霉病，其他如慢性坏死性肺曲霉病。该病诊断、治疗困难，患者死亡率高。为提高认识。对开滦医疗集团林西医院ICU2004年1月-2007年9月12例住院肺曲霉病患者进行总结，     

真菌性皮肤病

20111531对唑类药物交叉耐药的烟曲霉临床分离株耐药机制的初步探讨/孙毅(北大第一医院皮肤科),刘伟,陈伟…∥中华皮肤科杂志.-2011,44(4).-244～248自1例侵袭性曲霉病患者体内分离得到1株烟曲霉,分别采用微量液基稀释法和E-test法对该临床分离株进行常用抗真菌药物敏感性的测定。结果显     

真菌病

常见皮肤癣菌代谢产物体外对人角质形成细胞免疫活性的影响;少见致病性淡紫拟青霉的形态学研究;侵袭性曲霉病兔模型的构建;系统性真菌感染的药物治疗进展;伊曲康唑注射液治疗侵袭性真菌感染的肝脏安全性研究……[第一段]     

抗真菌药物新进展

按照化学结构分类简要介绍抗真菌药物的作用机制、药效学、独特的药代动力学以及目前相关指南对于曲霉病、念珠菌病等的管理。重点介绍了三种新上市的抗真菌药物,如艾沙康唑、艾氟康唑、Tavaborole。也介绍了某些抗真菌药物所具有的非抗真菌作用。     

侵袭性曲霉病的实验与临床研究

侵袭性曲霉病 (ｉｎｖａｓｉｖｅａｓｐｅｒｇｉｌｌｏｓｉｓ)是一种预后极为严重的深部真菌感染 ,多发生于有免疫缺陷的患者中 ,在深部真菌感染的发生率中 ,仅次于念珠菌感染列第二位[1] 。据英国医学真菌协会 (ＢＳＭＭ )和英国抗微生物化疗协会 (ＢＳＡＣ)所属的95家微生物实验室的统计资料 ,仅在英国每年根据实验室提供的资料协助而诊断的侵袭性曲霉病就达到 3 0 0～ 40 0例 ,而念珠菌菌血症达到 5 0 0～ 60 0例、隐球菌病 15 0例。但也有报道认为侵袭性曲霉病的发生率甚至超过深部念珠菌感染居第一位[2 ] 。侵袭性曲霉病在临床上常被原…     

毛霉病的治疗进展

毛霉病是一种侵袭感染真菌病,主要发生于免疫功能受抑制的患者,致死率高。毛霉病的治疗方法很多,外科手术清创联合有效的抗真菌药物是主要的治疗策略。治疗毛霉病的抗真菌药物有多烯类、唑类、棘白霉素类以及抗真菌药物联合治疗,其中最有效的药物为多烯类,其次是唑类抗真菌,最主要的唑类药有泊沙康唑,另外,伏立康唑和新的唑类药艾沙康唑也可治疗毛霉病。棘白霉素单独治疗毛霉疗效不佳,与其他抗真菌联合应用有协同治疗作用。铁螯合剂和高压氧的疗效尚待研究。两性霉素B脂质体作为首选治疗,而泊沙康唑是很有前景的治疗毛霉药物。早期积极联合治疗有助于降低毛霉病的死亡率。     

侵袭性曲霉病治疗进展

侵袭性曲霉病(invasive aspergillosis,IA)是由曲霉感染引起的较为严重的深部真菌感染性疾病.近年来,随着免疫抑制剂、广谱抗菌药物的广泛使用,器官移植技术等侵入性诊疗的普遍开展,以及恶性肿瘤、获得性免疫缺陷综合征患者人数的不断增加,IA发病率呈逐年上升趋势.如何降低IA的高死亡率是临床亟待解决的难题...     

真菌病

20072806院内侵袭性曲霉病的环境因素研究进展(综述)/吕雪莲(中国医科院皮研所),刘泽虎,刘维达∥国际皮肤性病学杂志.-2007,33(4).-253~255近年来医院内严重免疫缺陷患者的数量明显增加,其严重而长期的粒细胞缺乏是系统性真菌感染的主要易感因素。侵袭性曲霉病(IA)已成为血液病房、骨髓移植和实体器官移植中心患者的主要死因。研究发现,院内侵袭性曲霉病(NIA)不仅与免疫缺陷患者自身存在的易感因素有关,亦与建筑装修、季节等引发的医院环境,如空气、物体表面和水源的真菌污染,缺少有效环境监测和预防措施等因素密切相关。通过对NIA流行…     

急性侵袭性真菌感染治疗研究进展

近30年来,随着广谱抗生素、抗肿瘤药物、免疫抑制剂等的广泛应用,器官移植、骨髓移植、导管插管等的普遍开展,尤其是艾滋病等的流行,急性侵袭性真菌感染明显增多。但有关抗真菌的治疗药物也明显发展,这里就有关其近期研究进展做一回顾。     

Amphotericin B-resistant Aspergillus flavus infection successfully treated with caspofungin,a novel antifungal agent

Invasive aspergillosis is uncommon in immunocompetent hosts but is the second most common opportunistic fungal infection in immunocompromised patients. There has been a dramatic increase in the incidence of life-threatening aspergillosis during the past 2 decades, and the morbidity and mortality of these infections despite antifungal therapy remain unacceptably high. We describe a patient with amphotericin B-resistant Aspergillus flavus successfully treated with caspofungin, an agent belonging to a new class of antifungal drugs. Caspofungin shows great promise in the treatment of invasive aspergillosis.     

New antifungal agents

Currently, use of standard antifungal therapies can be limited because of toxicity, low efficacy rates, and drug resistance. New formulations are being prepared to improve absorption and efficacy of some of these standard therapies. Various new antifungals have demonstrated therapeutic potential. These new agents may provide additional options for the treatment of superficial fungal infections and they may help to overcome the limitations of current treatments. Liposomal formulations of AmB have a broad spectrum of activity against invasive fungi, such as Candida spp., C. neoformans, and Aspergillus spp., but not dermatophyte fungi. The liposomal AmB is associated with significantly less toxicity and good rates of efficacy, which compare or exceed that of standard AmB. These factors may provide enough of an advantage to patients to overcome the increased costs of these formulations. Three new azole drugs have been developed, and may be of use in both systemic and superficial fungal infections. Voriconazole, ravuconazole, and posaconazole are triazoles, with broad-spectrum activity. Voriconazole has a high bioavailability, and has been used with success in immunocompromised patients with invasive fungal infections. Ravuconazole has shown efficacy in candidiasis in immunocompromised patients, and onychomycosis in healthy patients. Preliminary in vivo studies with posaconazole indicated potential use in a variety of invasive fungal infections including oropharyngeal candidiasis. Echinocandins and pneumocandins are a new class of antifungals, which act as fungal cell wall beta-(1,3)-D-glucan synthase enzyme complex inhibitors. Caspofungin (MK-0991) is the first of the echinocandins to receive Food and Drug Administration approval for patients with invasive aspergillosis not responding or intolerant to other antifungal therapies, and has been effective in patients with oropharyngeal and esophageal candidiasis. Standardization of MIC value determination has improved the ability of scientists to detect drug resistance in fungal species. Cross-resistance of fungal species to antifungal drugs must be considered as a potential problem to future antifungal treatment, and so determination of susceptibility of fungal species to antifungal agents is an important component of information in development of new antifungal agents. Heterogeneity in susceptibility of species to azole antifungals has been noted. This heterogeneity suggests that there are differences in activity of azoles, and different mechanisms of resistance to the azoles, which may explain the present lack of cross-resistance between some azoles despite apparent structural similarities. The mechanisms of azole action and resistance themselves are not well understood, and further studies into azole susceptibility patterns are required.     

Six Novel Antimycotics

We have reviewed six new antimycotic agents which have potential applications for human cutaneous and mucosal diseases. Information on these six drugs was obtained via an English language search of PubMed through the US National Library of Medicine. The antimycotic agents reviewed include rilopirox, lanoconazole, NND-502, butenafine, eberconazole and voriconazole. Rilopirox is a synthetic pyridone derivative, related to ciclopirox, with a fungicidal action. Rilopirox is a hydrophobic, topical agent with potential application in mucosal candida infections, tinea versicolor and seborrheic dermatitis. Lanoconazole, an imidazole, is a topical agent with potential application in tinea infections and cutaneous candidiasis. The drug has been available for clinical use in Japan since 1994 and once-daily application to affected areas is recommended. In addition to its antifungal effect, animal data suggest that application of lanoconazole 0.5 or 1% cream is associated with accelerated wound healing. NND-502, a stereoselective analog of lanoconazole, is a topical agent with potential application in tinea pedis infection. NND-502 appears to be more effective in inhibiting ergosterol biosynthesis than lanoconazole or bifonazole and clinical trials comparing these agents are awaited. Butenafine is the first member of a new class of antifungals, the benzylamine derivatives, and has been approved for topical use in Japan (since 1992) and the US. Butenafine has a potent fungicidal action and the drug has been shown to be effective in multiple clinical trials in patients with tinea pedis, tinea corporis and tinea cruris. Butenafine has also been reported to exert an anti-inflammatory action after topical application and this may offer potential benefit over other topical antifungal agents. Eberconazole, an imidazole derivative, is a topical antifungal agent that has been shown to be effective in clinical trials in patients with tinea infections. Preliminary data indicate that the eberconazole is effective against some triazole-resistant yeasts such as Candida krusei and Candida glabrata. Voriconazole is an azole antifungal derivative of fluconazole. The drug is available in both oral and parenteral formulations. Oral voriconazole 200mg twice daily has been effective in treating oropharyngeal candidiasis and apergillosis in immunocompromised patients. After 12 weeks' treatment, a similar dosage of the drug elicited a positive response in 69% of nonimmunocompromised patients with invasive aspergillosis.     

侵袭性丝状真菌感染的流行病学趋势

随着感染真菌高危人群的增多,丝状真菌引起的侵袭性感染亦日益增多.虽然烟曲霉是最常见的病原菌,但非烟曲曲霉(如土曲霉)以及非曲霉丝状真菌(如镰刀霉属,赛多孢霉属及接合菌)也已经成为重要的感染因素.这些菌种对两性霉素B或其他常用的抗真菌药物天然耐药或不敏感,在临床上常导致较高的病死率.概述侵袭性丝状真菌感染的流行病学研究现状,旨在强调早期病原学诊断和选择敏感抗真菌药物的临床意义.

Abstract：

The prevalence of invasive filamentous fungal infections has been rising with the increase of high-risk population. Although Aspergillus fumigatus remains the most frequent cause of these infections, nonfumigatus Aspergillus species such as Aspergillus terreus and non-Aspergillus filamentous fungi such as Fusarium species, Scedosporium species and Zygomycetes have emerged as important pathogens. These fungal species are inherently resistant or less susceptible to amphotericin B or other antifungal drugs, and often cause a high mortality in patients. The epidemiology of invasive filamentous fungal infections is reviewed here to emphasize the clinical importance of early pathogenic diagnosis and selection of active antifungal agents.     

New antifungal agents.

This article, rather than presenting an overview of all available antifungal agents, has provided an update on new information about older agents, as well as evolving information about new agents, including those currently undergoing clinical trials. Among the azoles, ketoconazole will continue to be used as a major antifungal agent in dermatology, but one must keep up with its side effects and drug interactions. The place of the new triazole fluconazole in the treatment of cutaneous fungal infections needs to be clarified by additional controlled studies. Other agents on the horizon which are still undergoing investigation include itraconazole, which should be especially useful for dermatophyte (including tinea unguium) and candidal infections, sporotrichosis, and unusual infections such as aspergillosis and phaeohyphomycosis; and terbinafine, a member of the new class of antifungals called allylamines, which is an orally and topically active fungicidal agent that should be very useful for all types of dermatophyte infections. Research continues into the effectiveness of members of other classes of antifungals, including piritetrate, cilofungin, and amorolfine. In the 1990s, dermatologists should have safer, more effective antifungal agents for treating cutaneous fungal infections.     

红皮病型药疹并发声带烟曲霉病临床分析（附1例报告）

目的：初步探讨红皮病型药疹并发声带烟曲霉病的诱发因素、临床特点及治疗方法。方法：对我科1例红皮病型药疹并发声带烟曲霉病的病例进行回顾性分析。结果：并发声带烟曲霉病的诱因有多种，主要可能与使用激素有关，临床表现以声音嘶哑为主，手术切除病变组织、局部或系统抗真菌治疗均有效。结论：具有易感因素的患者出现声音嘶哑应注意并发声带烟曲霉病的可能。     

Advances in topical and systemic antifungals

Topical antifungal agents are generally used for the treatment of superficial fungal infections unless the infection is widespread, involves an extensive area, or is resistant to initial therapy. Systemic antifungals are often reserved for the treatment of onychomycosis, tinea capitis, superficial and systemic candidiasis, and prophylaxis and treatment of invasive fungal infections. With the development of resistant fungi strains and the increased incidence of life-threatening invasive fungal infections in immunocompromised patients, some previously effective traditional antifungal agents are subject to limitations including multidrug interactions, severe adverse effects, and their fungistatic mechanism of actions. Several new antifungal agents have demonstrated significant therapeutic benefits and have broadened clinicians' choices in the treatment of superficial and systemic invasive fungal infections.     

Voriconazole-induced retinoid-like photosensitivity in children

Voriconazole is a new triazole antifungal agent with activity against a wide range of systemic fungal pathogens, including Aspergillus spp. Photosensitivity is a rarely reported side effect of voriconazole, hypothesized to be a result of retinoid-like effects. We report two children with chronic granulomatous disease to whom voriconazole was administered for chronic invasive aspergillosis. Severe photosensitivity occurred in both patients, one of whom had striking photodamage at the 5-month follow-up.     

Muco-cutaneous retinoid-effects and facial erythema related to the novel triazole antifungal agent voriconazole

Voriconazole is a new azole antifungal drug with activity against a wide range of systemic fungal pathogens, including Aspergillus spp. Five patients with chronic invasive aspergillosis were treated for 12-58 weeks with voriconazole, 200 mg twice daily and developed facial erythema and cheilitis. One who received 58 weeks of therapy also developed discoid lupus erythematosus-like lesions on both sides of her neck. Both erythema and cheilitis resolved after discontinuation of voriconazole. Serum retinoids were elevated in the three patients in whom they were measured. Voriconazole has the potential for retinoid-like side-effects and facial erythema.     

院内侵袭性曲霉病的环境因素研究进展

随着院内免疫缺陷人群的增多，侵袭性曲霉病的发病率逐年增加。研究显示，院内曲霉感染不仅与宿主自身因素有关，亦和空气、水源、院内施工等环境因素密切相关。了解院内侵袭性曲霉病的流行病学、与环境真菌分布的相关性、环境真菌监控措施对降低其发病率、提高免疫缺陷宿主存活率具有重要意义。