两性霉素B脂质体、氟胞嘧啶和伊曲康唑联合治疗隐球菌性脑膜炎的临床回顾性研究

目的 观察两性霉素B脂质体、氟胞嘧啶和伊曲康唑联合治疗非AIDS、非器官移植隐球菌性脑膜炎患者的疗效和安全性,探讨非AIDS、非器官移植隐球菌性脑膜炎患者诱导治疗的新方案.方法 采用回顾性病例对照研究,18例非AIDS、非器官移植隐球菌性脑膜炎患者诱导期分别接受两性霉素B脂质体、氟胞嘧啶和伊曲康唑联合(研究组n=7)与两性霉素B、氟胞嘧啶和氟康唑联合治疗(对照组n=11).比较两组治疗方案在临床症状、体征变化、病死率、病原学转阴率、脑脊液改变等方面的差异及血常规、肝肾功能损害等不良反应发生情况.结果 治疗前研究组和对照组脑脊液新型隐球菌培养阳性分别为5例和8例(P =0.676),治疗1周后分别为5例和8例(P =0.676),治疗2周后分别为2例和4例(P =0.572),治疗3周后分别为0例和1例(P=0.611),治疗4周后,无死亡病例,两组脑脊液新型隐球菌培养均为阴性,脑脊液生化两组之间差异无统计学意义,对照组较研究组丙氨酸氨基转移酶(156.82±41.30 vs 97.00±22.02,P=0.003)、尿素氮(8.45±3.18 vs 5.54±1.28,P=0.020)升高更明显.结论 两性霉素B脂质体、氟胞嘧啶及伊曲康唑联合治疗非AIDS、非器官移植隐球菌性脑膜炎患者疗效确切,安全性较好,可以作为诱导期治疗的选择.     

静脉联合鞘内应用两性霉素B治疗隐球菌性脑膜炎23例的不良反应及疗效观察

目的探讨静脉联合鞘内应用两性霉素B(AmB)治疗隐球菌性脑膜炎(隐脑)的疗效及发生的不良反应。方法回顾性分析应用AmB治疗23例隐脑疗效及各种不良反应,以及不良反应的防治措施。结果23例患者静脉联合鞘内应用AmB治愈率78.3%,治疗过程中有20例发生各种不良反应,包括即刻反应、血细胞异常减少、肝肾功能损害、心脏毒性、低钾血症及静脉炎。其中以肾、肝功能损害及低钾血症最为多见,其发生比率分别为43.6%、40.0%、38.2%。结论静脉早期联合鞘内应用AmB治疗隐脑疗效明显,在长程治疗中会出现各种不良反应,应密切观察病情变化,定期随访,及时防治不良反应的发生。     

鞘内注射两性霉素 B 治疗隐球菌脑膜炎的 META 分析

目的 评价鞘内注射两性霉素B用于隐球菌脑膜炎患者治疗的有效性和安全性.方法 采用循证医学系统评价方法,检索Cochran图书馆注册临床对照试验数据库2012年第1期,PubMed、Ovid、Springer、外文生物医学期刊全文数据库,中国生物医学文献数据库、中文生物医学期刊文献数据库、中国知网、万方数据库、维普中文期刊数据库、中华医学会数字期刊数据库.文献检索时间从建库至2012年2月,纳入探讨鞘内注射两性霉素B治疗隐球菌脑膜炎的临床对照试验,并逐个进行质量评价和资料提取,运用RevMan 5.1.6软件进行统计分析.结果 共检出89篇文献,最终纳入6篇,涉及临床对照试验6项,纳入患者175例.Meta分析提示:鞘内注射给药组较对照组有效率高[OR =4.59,95％CI (2.19,9.64),P＜0.0001].可使脑膜刺激征持续时间平均缩短8.56 d(95％CI-11.74～-5.38,P＜0.000 01),但相应不良反应较多.结论 鞘内注射两性霉素B治疗隐球菌脑膜炎可以提高疗效,但较多的不良反应限制了其广泛应用,能否作为首选治疗手段有待于更大样本的高质量临床对照研究证实.     

52例新型隐球菌脑膜炎临床分析

新型隐球菌脑膜炎（Cryptococal neoformans menimgitis）是新型隐球菌引起的隐球菌病（cryptocaccol）,约占新型隐球菌感染的77％～80％,其临床表现不典型,误诊率高,病死率高,早期诊断,合理联合使用抗真菌药物治疗是提高隐球菌脑膜炎治愈率,降低病死率的关键。现对浙江大学医学院附属第一医院感染科2000年1月至2007年11月收治的52例新型隐球菌脑膜炎临床资料作回顾性分析,报道如下。     

隐球菌性脑膜炎的诊断与治疗

隐球菌性脑膜炎是由隐球菌属,特别是新生隐球菌及格特隐球菌引起的机会性感染,在免疫抑制者及正常人群均可发病。隐球菌性脑膜炎早期诊断困难,即便接受治疗,患者死亡率仍然很高。在过去几年中,快速及时的检测及早期隐球菌抗原检查取得了重大进展。对晚期HIV感染者行血隐球菌荚膜抗原筛查并进行抢先治疗,有望阻止其进展为临床感染。目前抗真菌药物主要包括多烯类、唑类及氟胞嘧啶,未来药物研究的重点是疗效更好、毒性更小的新型口服抗真菌药。本文总结近几年隐球菌性脑膜炎的相关诊断及治疗进展,旨在对隐脑患者诊疗提供帮助。     

45例新型隐球菌脑膜炎死亡原因分析

我科１９９０～１９９７年１２月共收治新型隐球菌脑膜炎１０４例，死亡４５例，现分析如下。１临床资料１．１一般资料４５例中，男２７例、女１８例，年龄９～５８岁，起病呈急性１３例（２９％），亚急性１４例（３１％），慢性１８例（４０％），发病前有慢性或恶性疾...     

30例隐球菌脑膜炎治疗引起的肝损及防治

新型隐球菌脑膜炎（隐脑）是由新型隐球菌感染引起的脑膜炎,是中枢神经系统最常见的真菌感染,其病情重、病死率高。目前国内外学者一致推荐两性霉素B（AMB）、5-氟胞嘧啶（5FC）、氟康唑（FCZ）作为治疗隐脑的主要药物。但因这些药物引起不良反应较显著：有即刻反应、外周血象白血球减少、低钾血症,有肝损,其中肝功能损害发生率高,故了解AMB、5FC、FCZ的不良反应及其防治显得尤为重要。     

类肿瘤样肺部真菌感染的CT征象分析

目的分析形态学上类似肿瘤样病变的肺部真菌感染的CT征象,以提高认识,减少误诊。方法回顾性分析53例经手术病理证实的类肿瘤样肺部真菌感染的基本临床资料及CT表现。结果 53例类肿瘤样肺部真菌感染中32(60.4%)例为隐球菌感染,21(39.6%)例为曲霉菌感染。29(54.7%)例为单发病灶,24(45.3%)例为多发病灶。CT表现为实性肺结节的30(56.6%)例,表现为实性肺部肿块的10(18.9%)例,两者都有的13(24.5%)例。病灶大小1~7 cm,中位大小2.5 cm。53例中病灶位于胸膜下32(60.4%)例,肺内其他部位21(39.6%)例。隐球菌和曲霉菌在病灶特征、形态、分叶征、毛刺征、晕征及其他伴随病变如片状浸润灶、粟粒样结节、淋巴结肿大、胸膜增厚、胸腔积液等方面差异无统计学意义(P0.05),在病灶部位(χ2=10.633)、边界(χ2=4.828)及病灶内有无空洞或空腔性病变(χ2=18.702)等方面差异有统计学意义(P0.05)。结论类肿瘤样肺部真菌感染以隐球菌及曲霉菌感染多见,两种真菌感染CT表现具有一定特征性,结合临床可与肺内恶性肿瘤进行鉴别。     

两性霉素B治疗艾滋病合并隐球菌性脑膜脑炎40例临床特征及诊疗分析CSCD

目的分析两性霉素B治疗艾滋病合并隐球菌性脑膜脑炎的临床特点、药物治疗不良事件情况,寻找发生不良事件的相关危险因素,为隐球菌性性脑膜脑炎临床诊治提供参考。方法回顾性分析我院2017年1月至2018年12月诊断为艾滋病合并隐球菌性脑膜脑炎住院患者基本资料,对实验室检测结果、药物治疗方案、不良事件等资料进行收集、分析。结果40例艾滋病合并隐球菌性性脑膜脑炎患者平均年龄为(40.54±15.42)岁,住院天数为(32.67±12.22)d,颅内压升高30例(75.0%),脑脊液隐球菌抗原阳性37例(92.5%),脑脊液培养阳性31例(77.5%),脑脊液墨汁染色涂片阳性34例(85.0%),诱导期治疗方案选择两性霉素B联合氟胞嘧啶,在治疗过程中,发生不良事件最多的是贫血22例(55.0%),其次是低钾17例(42.5%);血红蛋白(hemoglobin,HGB)、血钾指标出现明显异常时间主要在药物使用的第2周,肌酐、总胆红素、谷丙转氨酶指标出现明显异常时间主要药物使用的第1周。两性霉素B累计使用剂量>500 mg、治疗前HGB<110 g/L是导致患者治疗疗程<14 d的影响因素,差异有统计学意义(P=0.001;P=0.006)。结论艾滋病合并隐球菌性性脑膜脑炎患者在使用两性霉素B药物治疗过程中,不同时间点发生不良事件有所不同,影响药物使用天数的因素主要是药物累计使用剂量、治疗前HGB水平。     

脑脊液墨汁涂片阴性的儿童隐球菌脑膜炎1例:诊断与治疗

报道1例长期脑脊液墨汁涂片均为阴性的儿童隐球菌脑膜炎,并对此病的诊断方法进行探讨。脑脊液真菌培养和鉴定仍然应该是隐球菌脑膜炎诊断的“金标准”,脑脊液乳胶凝集实验结合真菌培养结果可以对此病的快速诊断做出早期提示,对脑脊液墨汁涂片阴性的检查结果需要结合其他指标进行综合考虑做出判断。     

Combined effect of furanone fluconazole and amphotericin B against biofilms formed from Cryptococcus neoformans

It is of interest to document the combined effect of furanone fluconazole and amphotericin B against the biofilm formed by Cryptococcus neoformans. The MIC values of amphotericine B and Fluconazole were observed as 20µg/ml and 60µg/ml, respectively. The MIC for the Combination (Amphotericin B/ Fluconazole) was found to be at (15/20) µg/ml drug concentration. Thus, data shows the combined effect of furanone fluconazole and amphotericine B derivative against C. neoformans.     

CD44在隐球菌性脑膜炎发病机制中的作用研究

目的测定隐球菌性脑膜炎小鼠脑组织中CD44表达,探讨CD44在隐球菌性脑膜炎发病机制中的作用。方法隐球菌性脑膜炎免疫抑制小鼠为实验组,未接种隐球菌的免疫抑制小鼠为对照组,应用免疫组化法检测实验组6h、12h、24h、48h、72h、4d、7d小鼠脑组织CD44表达与对照组的变化。结果对照组小鼠脑组织CD44均匀分布在脑细胞膜上。实验组隐球菌作用小鼠48h、72h后,CD44在小鼠脑组织脑膜侧分布增加,而在脑实质侧CD44的分布明显减少。病灶周围的脑组织CD44分布也一侧增加,另一侧分布减少。结论隐球菌侵入小鼠脑组织后,隐球菌诱导CD44向脑组织的一侧移行,向脑膜方向聚集。病灶周围脑组织CD44分布也不均匀。说明隐球菌性脑膜炎的发生与CD44有密切的关系。     

Unique hybrids between the fungal pathogens Cryptococcus neoformans and Cryptococcus gattii

Cryptococcus neoformans and Cryptococcus gattii are yeasts that cause meningoencephalitis, but that differ in host range and geographical distribution. Cryptococcus neoformans occurs world-wide and mostly infects immunocompromised patients, whereas C. gattii occurs mainly in (sub)tropical regions and infects healthy individuals. Anomalous C. neoformans strains were isolated from patients. These strains were found to be monokaryotic, and diploid or aneuploid. Amplified Fragment Length Polymorphism (AFLP) and sequence analyses indicated that AFLP genotypes 2 (C. neoformans) and 4 (C. gattii) were present. The strains were serologically BD. Mating- and serotype-specific PCR reactions showed that the strains were MATa-serotype D/MATalpha-serotype B. This study is the first to describe naturally occurring hybrids between C. neoformans and C. gattii.     

Cryptococcosis in Colombian children and literature review

Cryptococcosis is reported in adults and is often acquired immune deficiency syndrome (AIDS)-associated; however, its frequency in children is low. Based on the National Survey on Cryptococcosis conducted in Colombia, an epidemiological and clinical analysis was performed on cases of the disease observed in children less than 16 years old between 1993-2010. We found 41 affected children (2.6% prevalence) from the 1,578 surveys received. The country mean annual incidence rate was 0.017 cases/100,000 children under 16 years, while in Norte de Santander the incidence rate was 0.122 cases/100,000 (p < 0.0001). The average age of infected children was 8.4 and 58.5% were male. In 46.3% of cases, a risk factor was not identified, while 24.4% had AIDS. The most frequent clinical manifestations were headache (78.1%), fever (68.8%), nausea and vomiting (65.6%), confusion (50%) and meningeal signs (37.5%). Meningitis was the most frequent clinical presentation (87.8%). Amphotericin B was given to 93.5% of patients as an initial treatment. Positive microbiological identification was accomplished by India ink (94.7%), latex in cerebrospinal fluid (100%) and culture (89.5%). Out of 34 isolates studied, Cryptococcus neoformans var. grubii (VNI 85.3%, VNII 8.8%) was isolated in 94.1% of cases and Cryptococcus gattii (VGII) was isolated in 5.9% of cases. These data are complemented by a literature review, which overall suggests that cryptococcosis in children is an unusual event worldwide.     

不同中枢神经系统感染患儿血清和脑脊液炎症标记物及MMP-9水平及临床意义

摘要 目的：探讨不同中枢神经系统感染患儿血清和脑脊液中炎症标记物及基质金属蛋白酶9（Matrix metallo protein 9,MMP-9）的水平及临床意义。方法：选取本院2017年8月至2018年6月收治的198例脑膜炎儿童患者分为感染组,根据不同患病原因分成化脓性脑膜炎（Purulent Meningitis, PM=107例）和病毒性脑膜炎（Viral Meningitis, VM=91例）,另选取同期58例体检健康儿童作为对照组（Normal Control, NC=58例）。采用双抗夹心免疫荧光发光法检测患者血清和脑脊液（Cerebrospinal fluid,CF）中降钙素原（Prcoalcitonin,PCT）水平;采用免疫荧光分析仪检测患者血清和脑脊液内C反应蛋白（C-reactionprotein,CRP）水平;酶联免疫吸附实验（ELISA）检测三组患儿治疗前后血清和脑脊肿瘤坏死因子-α(Tumor necrosis factor-α, TNF-α)及MMP-9表达水平;电化学发光全自动免疫分析仪分析血清白蛋白和脑脊液白蛋白含量,并计算白蛋白指数。结果：与对照组相比,化脑组和病脑组患儿血清和脑脊液中CRP、PCT、TNF-α及MMP-9水平均明显增高（P<0.05）,化脑组患儿血清和脑脊液中CRP、PCT、TNF-α及MMP-9水平显著高于病脑组（P<0.05）。与对照组相比,化脑组患儿治疗前、治疗72小时和治疗1周后血清和脑脊液PCT水平降低（P<0.05）,与对照组相比,病脑组患儿治疗前后血清和脑脊液PCT水平表达差异无统计学意义（P>0.05）;化脑组和病脑组患儿脑脊液中CRP、PCT、TNF-α及MMP-9水平与患儿白蛋白指数均呈正相关。结论：血清和脑脊液炎症标记物及MMP-9变化可对化脓性脑膜炎和病毒性脑膜炎进行初步的鉴别。     

基质金属蛋白酶与中枢神经系统感染

基质金属蛋白酶(MMPs)是一组合锌的能降解细胞外基质的中性蛋白酶家族.目前认为MMPs尤其是明胶酶(MMP-2,MMP-9)与中枢神经系统感染关系密切.通常它们以酶原的形式存在,一旦活化,则迅速攻击血脑屏障,降解基底膜的一些基质蛋白,破坏内皮细胞的紧密连接蛋白,促进脑水肿的形成和炎细胞的浸润.近年来研究发现,中枢神经系统感染后MMPs表达增加.导致血脑屏障损害及血管源性脑水肿,并参与中枢神经系统免疫反应,促进感染的病理生理过程.     

Resistance to amphotericin B associated with defective sterol Δ8→7 isomerase in a Cryptococcus neoformans strain from an AIDS patient

Abstract Two Cryptococcus neoformans strains isolated from an AIDS patient were investigated, a pretreatment isolate (CN1) and a second isolate (CN3) following failure of fluconazole and amphotericin B treatment. No difference in fluconazole sensitivity, but relative resistance to amphotericin B was observed for CN3. The sterol composition of CN3 indicated a defect in sterol Δ ^8→7 isomerase in this strain and depletion of ergosterol, the major sterol of the CN1.     

Two-component signal transduction in human fungal pathogens

Signal transduction pathways provide mechanisms for adaptation to stress conditions. One of the most studied of these pathways is the HOG1 MAP kinase pathway that in Saccharomyces cerevisiae is used to adapt cells to osmostress. The HOG1 MAPK has also been studied in Candida albicans, and more recently observations on the Hog1p functions have been described in two other human pathogens, Aspergillus fumigatus and Cryptococcus neoformans. The important, but not surprising, concept is that this pathway is used for different yet similar functions in each of these fungi, given their need to adapt to different environmental signals. Current studies of C. albicans focus upon the identification of two-component signal proteins that, in both C. albicans and S. cerevisiae, regulate the HOG1 MAPK. In C. albicans, these proteins regulate cell wall biosynthesis (and, therefore, adherence to host cells), osmotic and oxidant adaptation, white-opaque switching, morphogenesis, and virulence of the organism.     

Primary Central Nervous System Infection by Histoplasma in an Immunocompetent Adult

Mycopathologia - Central nervous system (CNS) infection by Histoplasma capsulatum is a rare disease in immunocompromised individuals in endemic areas. About one quarter of cases result from...     

Antimicrobial susceptibility testing of dematiaceous filamentous fungi: Effect of medium composition at different temperatures and times of reading

We examined the effects of the composition of five media on the MICs of three antifungal agents (amphotericin B, flucytosine and ketoconazole) against 24 dematiaceous fungi at different temperatures and times of reading. Media studied were RPMI 1640, tryptic soy broth (TSB), yeast nitrogen broth (YNB), casein-yeast-glucose broth (CYG) and high-resolution medium (HR). The degree of reproducibility was determined with ketoconazole and 5-fluorocytosine and the media TSB and RPMI showed the best results with ketoconazole, while the best results for flucytosine were in CYG. Reproducibility was higher at 25° than at 30 °C. The media and incubation time were shown to have a significant influence on the MICs of the three antifungals, but there were no interactions between these variables and temperature, except in the case of ketoconazole, where media-temperature and media-incubation time interactions were significant. There were noteworthy differences between the MICs obtained with the different media. This revised version was published online in June 2006 with corrections to the Cover Date.