微创下早期诊断真菌感染的临床研究

目的探讨真菌感染早期的病理诊断方法,提高真菌阳性检出率,有效指导临床治疗。方法将2011年至2013年痰、胸水、腹水、表面皮肤刮片等脱落细胞标本,经薄层液基细胞制片(TCT)检测选取78例标本,对标本制备的细胞块连续切片经特殊染色PAS、免疫组化MUC5B、原位杂交念珠菌探针方法,对患者年龄、性别及健康状况的真菌阳性率进行数据分析,对PAS、MUC5B两种检测方法的相关性进行分析,比较传统及科研检测早期诊断真菌感染的方法差异性。结果 78例标本中三种检测方法在年龄组、性别组均无统计学差异(P>0.05),PAS在健康状况组无统计学差异(P>0.05),MUC5B、念珠菌探针在健康状况组中均有统计学差异(P<0.05);PAS与MUC5B表达的统计学分析有统计学差异,两者之间具有相关性(P<0.05,r=0.236),传统及科研检测早期诊断真菌感染的方法进行比较具有统计学差异(P<0.01)。结论通过数据统计健康状况较差的人群中真菌抗体MUC5B及念珠菌检出率高于健康状况良好的人群;MUC5B真菌阳性检出率显著高于PAS染色;本科研方法真菌阳性检出率明显高于传统真菌检测方法;采用PAS与MUC5B及念珠菌探针联合应用能提高真菌阳性检出率及达到对真菌的初步分类。     

荧光染色在鼻窦真菌快速诊断中的应用评价

目的评价荧光染色在快速诊断真菌性鼻-鼻窦炎中的应用效果。方法对96例2017年7月至2018年4月首都医科大学附属北京同仁医院临床诊断为真菌性鼻-鼻窦炎的患者术中留取少量真菌团块组织,拉片制成薄层涂片,滴适量荧光染料,加盖玻片,室温放置5 min,在荧光显微镜下从低倍至高倍观察真菌结构。常规进行乳酸酚棉蓝染色及1.79 mol/L KOH湿片处理,以真菌培养结果作为金标准。真菌培养阴性、镜检阳性的样本提取核酸通过ITS序列扩增,进行真菌成分的分子检测。结果荧光染色、乳酸酚棉蓝染色、1.79 mol/L KOH湿片标本一次镜检阳性率分别为95.83%(92/96),93.75%(90/96)及91.67%(88/96),差异无统计学意义;涂片阴性标本再次涂片染色镜检,除1.79 mol/L KOH漏检2例外,荧光及乳酸酚棉蓝染色均可捕捉到真菌结构。培养阳性的65例标本,荧光着色理想,可见清晰的真菌结构,尤其对曲霉菌属与暗色真菌属菌丝区分良好,直接荧光染色拟诊与培养结果一致。有3例经乳酸酚棉蓝染色及1.79 mol/L KOH湿片观察到特征性顶囊结构及分生孢子判断为烟曲霉及链格孢属,结果与培养一致,而荧光染色此类结构着色不清。31例镜检阳性、培养阴性的样本分子检测结果显示,黄曲霉9例、烟曲霉3例、杂色曲霉1例、产黄青霉1例、链格孢霉属2例、尖端赛多孢1例、近平滑假丝酵母菌1例,13例样本为阴性结果。结论荧光染色法可用于鼻窦真菌的快速拟诊,但在观察真菌特征性产孢及产色素结构上,与常规方法相比并无显著优势。     

真菌性角膜炎致病菌种的变迁及体外药物敏感试验研究

目的 回顾分析2000-2006年山东省真菌性角膜炎致病菌菌种的分布、变迁及部分常见致病菌时抗真菌药物的敏感性.方法 对真菌性角膜炎患者的溃疡组织刮片和角膜移植术中取下的病变角膜片标本进行真菌培养及菌种鉴定,分析致病菌的构成及其随年份的变化和山东省眼科研究所开展真菌体外药敏试验以来的试验结果 .结果 2000-2006年间,共有898例患者诊断为真菌性角膜炎,770例(85.7%)真菌培养阳性.其中首位的致病菌属为镰刀菌属(547例,71.0%),历年百分比分别为75.5%、72.8%、71.5%、75.2%、76%、68.8%和56.4%;曲霉菌属(84例,10.9%)是第2位的致病菌,历年所占百分比为15.1%、15.2%、13.1%、10.2%、10.4%、8.0%和6.9%;链格孢属(74例,9.6%)位居第3位,历年所占百分比分别为1.9%、3.3%、3.7%、6.6%、8.8%、12.0%和29.7%.镰刀菌属主要菌种为茄病镰刀菌(33.8%)、尖孢镰刀菌(28.2%)与串珠镰刀菌(27.4%);曲霉菌属主要菌种为黄曲霉(53.6%)与烟曲霉菌(39.3%).常见真菌对两性霉素B、特比萘芬、伊曲康唑、5-氟胞嘧啶和氟康唑MIC值的几何均数分别为0.647、0.714、1.624、15.108和27.070 μg/ml.镰刀菌属5种抗真菌药物MIC的几何均数分别为0.899、0.893、3.077、37.124和21.687 μg/ml;曲霉菌属分别为0.794、0.591、0.416、23.973和7.127 μg/ml;链格孢属分别为0.409、0.479、0.433、11.655和7.104 μg/ml.结论 镰刀菌属、曲霉菌属和链格孢属是山东省真菌性角膜炎前3位的致病菌属.2000至2006年间,镰刀菌属始终居于真菌性角膜炎致病菌的首位;其次为曲霉菌属,比例呈下降趋势;链格孢属居于第3位,比例呈逐年升高趋势.镰刀菌属对两性霉素B和特比萘芬MIC值的几何均数低,对伊曲康唑、5-氟胞嘧啶和氟康唑MIC值的几何均数高.曲霉菌属和链格孢属对5种抗真菌药物MIC值的几何均数较镰刀菌都低.     

胃上皮异型增生在印戒细胞癌发生中的作用

目的:探讨上皮异型增生在胃印戒细胞癌发生中的作用.方法:以42例早期胃印戒细胞癌为研究材料,AB-PAS(奥辛蓝-过碘酸雪夫)染色观察印戒细胞和癌旁异型增生所舍黏液的组织化学特性;免疫组化染色检测两者表达胃和肠上皮标志物MUC5AC,MUC6,MUC2,CD10的情况,并将印戒细胞和异型增生分为G型(胃型)、GI型(胃肠型)、I型(肠型)和U型(未分化型)四类,统计并比较印戒细胞、癌旁异型增生的类型.以20例早期肠型胃癌作为对照.结果:AB-PAS染色显示,印戒细胞所含的黏液主要为中性及混合性黏液,癌旁异型增生上皮分泌的黏液成分与印戒细胞一致;免疫组织化学染色显示,印戒细胞的分类以G型为主,癌旁异型增生G型更多见,而I型少见;G型、GI型异型增生可向印戒细胞癌移行,且在GI型异型增生移行为印戒细胞癌时,肠上皮标志物的表达逐渐下降.结论:印戒细胞癌的发生与上皮异型增生有关,而伴有胃型上皮分化的异型增生可能是印戒细胞癌的癌前病变.     

单侧上颌窦病变56例临床分析

目的:探讨单侧上颌窦混浊的病因与治疗方法.方法:回顾性分析以慢性鼻窦炎症状为主诉的56例患者,CT证实为单侧上颌窦混浊,所有患者术前及术后6个月进行生存质量、鼻内镜检查和鼻窦CT评分.结果:56例患者均实施鼻内镜手术,术后病理证实有24例慢性鼻窦炎不伴息肉,13例慢性鼻窦炎伴鼻息肉,9例真菌球型鼻窦炎,5例黏液囊肿,3例内翻乳头状瘤, 2例变应性真菌性鼻窦炎.结论:单侧上颌窦混浊相当普遍,乳头状瘤、黏液囊肿、真菌球型鼻窦炎和变应性真菌性鼻窦炎应尽早实施手术,慢性鼻窦炎(伴或不伴息肉)可早期实行保守治疗.     

鼻内镜下治疗非侵袭性真菌性鼻窦炎35例

目的探讨真菌性鼻窦炎的鼻内镜手术治疗、影像学诊断及其与鼻腔解剖异常之间的关系。方法分析35例经病理学确诊的真菌性鼻窦炎的术前诊断、术中所见和治疗结果。结果 CT扫描或鼻内镜检查显示35例患者鼻腔均有不同程度的解剖异常或病变及窦腔内病灶;全部病例病理学检查确诊为真菌病变(曲霉菌)。临床分型均属非侵袭性真菌性鼻窦炎。术后随访1～3年,一期治愈34例(97%)。结论鼻腔局部解剖结构异常及病变与真菌性鼻窦炎关系密切;鼻窦CT扫描结合鼻内镜检查是诊断真菌性鼻窦炎的重要方法;鼻内镜手术清除病灶是治疗非侵袭性真菌性鼻窦炎的有效方法。     

1050例鼻窦炎病原菌分析

目的 探讨引起鼻窦炎的病原微生物分布及与鼻窦炎感染类型的关系。为临床医生提供诊断和治疗的依据。方法 对2013-2017年诊治的1 050例鼻窦炎患者,通过鼻内窥镜手术所取的窦腔内容物行标本直接涂片镜检,普通细菌培养、真菌培养、厌氧菌培养和质谱仪菌种鉴定。结果 1 050例鼻窦炎患者分为急性鼻窦炎患者164例、慢性鼻窦炎患者384例和真菌性鼻窦炎患者502例。细菌直接涂片和培养结果一致,2013年~2016年真菌涂片镜检的总体阳性率66.5%,培养阳性率44.0%, 2017年改进了真菌培养前处理方法后培养阳性率87.1%,涂片镜检的阳性率68.8%,真菌涂片阳性率高于培养结果。经培养鉴定共检出1283株病原菌,排在前几位的细菌分别是：金黄色葡萄球菌177株（13.8%）、铜绿假单胞菌101株（7.9%）和流感嗜血杆菌78株（6.1%）为主,其次为链球菌属90株（7.0%）和克雷伯菌54株（4.2%）;厌氧菌主要为普雷沃菌14株（1.0%）、具核梭杆菌5株（0.1%）;真菌以曲霉菌200株（15.6%）为主,多伴有细菌的混合感染。急性鼻窦炎多为一种病原,慢性鼻窦炎多混合2种以上病原菌,急性和慢性鼻窦炎病原菌的种类和排序无明显差异。结论 急性和慢性鼻窦炎的致病细菌以金黄色葡萄球菌、铜绿假单胞菌和流感嗜血杆菌为主,厌氧菌多为普雷沃菌和具核梭杆菌;真菌性鼻窦炎以曲霉菌属为主,同时伴有细菌的混合感染;临床应根据细菌和真菌培养结果合理用药。     

34例鼻窦真菌感染的病原菌分析

目的探讨鼻窦部位真菌感染的致病菌种，同时为临床医生提供诊断依据。方法将３４份鼻窦腔内分泌物做涂片直接镜检、接种培养，鉴定菌种。结果直接镜检３３例阳性。真菌培养２２例阳性，其中曲霉菌１８例、尖端足分枝菌２例、波氏假性霉样真菌、链格孢菌各１例。结论鼻窦真菌感染的致病菌以曲霉菌为主     

甲状腺透明细胞型乳头状癌临床病理观察

目的探讨甲状腺透明细胞型乳头状癌的临床病理特征、免疫表型、诊断及鉴别诊断要点。方法对1例甲状腺肿瘤的临床病理资料进行光镜观察及免疫组化和AB-PAS染色,并复习相关文献。结果患者女性,60岁。肿瘤位于甲状腺峡部,大体呈结节状,似有完整包膜,切面五彩状,可见黏液及钙化。组织学见肿瘤由充满胶质或稀薄黏液的滤泡结构和实性片状区域构成,未见明确乳头结构,但可见泡状核、核沟及核内假包涵体,引人注目的是实性区域部分细胞胞质透明。免疫组化显示TTF-1、Tg、galectin-3和CK19(+),HBME-1、降钙素、CD10、RCC和vimentin(-)。特殊染色:AB-PAS(+)。结论甲状腺透明细胞型乳头状癌是甲状腺乳头状癌的罕见亚型,组织形态学易与转移性肾透明细胞癌混淆,免疫组化及PAS染色有助于二者的鉴别。     

微波辐射PAS染色显示声带鳞状细胞癌早期的基底膜改变

目的观察微波辐射PAS染色法显示声带鳞状细胞癌早期基底膜改变的效果。方法对89例声带早期鳞状细胞癌改变的病理切片进行微波辐射PAS染色和传统PAS染色,比较两者显示基底膜的效果,并通过层黏连蛋白的免疫组化EnVision二步法对两种PAS染色结果进行验证。结果两种PAS染色结果与层黏连蛋白的染色结果一致。HE染色怀疑有微小浸润者52例,其中PAS染色显示43例可疑微浸润灶周边基底膜样物质消失或部分缺失,证实有微浸润;9例疑似微浸润灶周边有完整的基底膜着色,证实为上皮脚横切或斜切面造成的假象。另外,微波辐射PAS染色时间为15 min,传统PAS染色时间为56 min,微波辐射PAS染色显示基底膜较传统PAS染色清晰(P<0.001)。结论微波辐射PAS染色显示声带鳞状细胞癌早期改变基底膜的结果可靠,并可显著缩短显示时间,提高传统PAS染色显示基底膜的效果。     

儿科患者中真菌分布及耐药监测

目的了解我院2000-2006年临床深部真菌感染分离的病原真菌种类及对抗真菌药物的耐药性变化。方法分析2000年1月～2006年12月年我院住院患儿所有送检真菌培养标本中分离出的菌株，药敏试验使用ATB-FUNGUS2INT酵母药敏试条，进行5-氟胞嘧啶、氟康唑和两性霉素B3种抗真菌药敏检测，严格按照2006年CLSIM27-A2规则及标准进行。结果分离出635株真菌中，念珠菌属572株（90．1％），曲霉属29株（4．6％），隐球菌属21株（3．3％），青霉属和酵母属各5株（0．8％），毛孢菌属2株（0．3％），毛霉属1株（0．2％）。念珠菌属中，前3位分离菌是白念珠菌418株（73．1％）；光滑念珠菌64株（11．2％）；热带念珠菌52株（9．1％）。白念珠菌对5-氟胞嘧啶、氟康唑和两性霉素B敏感率分别为97．6％，97．6％和98．4％。结论儿科患者中分离的真菌中以念珠菌属最多，并以白念珠菌为主，曲霉比率也在增多。5-氟胞嘧啶、氟康唑和两性霉素B均有较高的抗真菌活性。应加强真菌分离鉴定和耐药性监测，供合理选用抗真菌药物的参考。     

国产伏立康唑对临床分离病原真菌体外抗菌活性研究

目的了解国产伏立康唑对北京和我国其他地区临床分离的常见病原真菌体外抗菌活性。方法分别参照CLSIM27-A2和M38-A方案测定伏立康唑对144株酵母和82株产孢丝状真菌的抗菌活性。受试菌株包括念珠菌114株（含氟康唑获得性耐药白念珠菌）、新型隐球菌20株、阿萨希毛孢子菌10株、曲霉62株（含伊曲康唑耐药曲霉及两性霉素B不敏感曲霉）、镰刀菌10株、尖端赛多孢菌10株。结果伏立康唑对念珠菌（不包括氟康唑耐药和剂量依赖敏感白念珠菌）、新型隐球菌、阿萨希毛孢子菌的MIC50≤0．5mg／L、MIC90≤1mg／L；而对氟康唑获得性耐药白念珠菌MIC50和MIC90均〉16mg／L。对曲霉、尖端赛多孢菌的MIC50≤1mg／L、MIC90≤2mg／L，对镰刀菌的MIC50和MIC90分别为4mg／L和〉16mg／L。结论伏立康唑对多数酵母有较强的体外抗菌活性，尤其是对克柔念珠菌和光滑念珠菌等氟康唑天然耐药菌株。该药对多数产孢丝状真菌也有较好的体外抗菌作用，包括伊曲康唑耐药及两性霉素B不敏感的曲霉以及对多种抗真菌药物耐药的尖端赛多孢菌；但其对氟康唑获得性耐药白念珠菌有一定交叉耐药。     

Antifungal activity of saperconazole (R 66 905) in vitro

Saperconazole, a novel orally active triazole antifungal, inhibited Candida spp., Aspergillus spp. and dermatophyte fungi in vitro. Its minimal inhibitory concentrations for Candida spp. and dermatophytes were relatively high, like those of comparable triazole antifungals, but all of the Aspergillus isolates tested were inhibited by less than 0.1 mg/l. Relative inhibition factors of saperconazole were in the range 31-76% for Candida isolates, 6-18% for Aspergillus isolates and 5-10% for dermatophytes. These figures predict a good inhibitory activity of saperconazole for all the fungi tested, with particularly strong activity against Aspergillus spp. and dermatophytes. Saperconazole inhibited hyphal branch formation in C. albicans at concentrations as low as 10(8) M.     

In Vitro Antifungal Activity of Nikkomycin Z in Combination with Fluconazole or Itraconazole

Nikkomycins are nucleoside-peptide antibiotics produced by Streptomyces species with antifungal activities through the inhibition of chitin synthesis. We investigated the antifungal activities of nikkomycin Z alone and in combination with fluconazole and itraconazole. Checkerboard synergy studies were carried out by a macrobroth dilution procedure with RPMI 1640 medium at pH 6.0. At least 10 strains of the following fungi were tested: Candida albicans, other Candida spp., Cryptococcus neoformans, Coccidioides immitis, Aspergillus spp., and dematiacious fungi (including Exophiala jeanselmei, Exophiala spinifera, Bipolaris spicifera, Wangiella dermatitidis, Ochroconis humicola, Phaeoannellomyces werneckii, and Cladophialophora bantiana), and 2 strains each of Fusarium, Scedosporium, Paecilomyces, Penicillium, and Trichoderma spp. A total of 110 isolates were examined. Inocula of fungal elements were standardized by hemacytometer counting or spectrophotometrically. MICs and minimum lethal concentrations (MLCs) were determined visually by comparison of growth in drug-treated tubes with growth in drug-free control tubes. Additive and synergistic interactions between nikkomycin and either fluconazole or itraconazole were observed against C. albicans, Candida parapsilosis, Cryptococcus neoformans, and Coccidioides immitis. Marked synergism was also observed between nikkomycin and itraconazole against Aspergillus fumigatus and Aspergillus flavus. No antagonistic interaction between the drugs was observed with any of the strains tested.     

Effects of culture media on the in vitro susceptibility of selected opportunistic fungi to fluconazole and itraconazole.

The sensitivity of 23 isolates of opportunistic fungi, Aspergillus fumigatus (5), A. flavus (5), A. niger (5), Pseudallescheria boydii (5), Alternaria alternata (2) and Xylohypha bantiana (1), was investigated against fluconazole and itraconazole, using Sabouraud's dextrose broth (SD) and a high-resolution (HR) medium (Pfizer, Inc.). The procedure followed was a standard tube dilution (1 ml/tube) method. Candida albicans Y01 09 was included as reference strain to monitor quality and reproducibility. Results indicated that the minimal inhibitory concentrations (MICs) of fluconazole for all Aspergillus spp. and C. albicans were greater than or equal to 100 micrograms/ml in SD medium, whereas, for P. boydi, A. alternata and X. bantiana, the MICs were 50 micrograms/l. The MICs of itraconazole in SD medium were less than 0.195-1.56 micrograms/ml for the fungi tested. In HR medium, the MICs of fluconazole for the Aspergillus spp, were greater than or equal to 100 micrograms/ml, and those for P. boydii, A. alternata and X. bantiana were 0.78, 50 and 50 micrograms/ml, respectively. The MICs of itraconazole for all fungi ranged from less than 0.198 to 0.78 micrograms/ml in the HR medium. The values for the reference strain were 1.56 and 100 micrograms/ml in the HR medium for fluconazole and itraconazole, respectively. The HR medium was more suitable for testing P. boydii against fluconazole. This culture medium did not appear to significantly affect the MICs of itraconazole as compared to those of fluconazole, for the fungi investigated.     

The antifungal echinocandin caspofungin acetate kills growing cells of Aspergillus fumigatus in vitro

Caspofungin acetate is an antifungal antibiotic that inhibits synthesis of 1,3-beta-D-glucan, an essential component of the fungal cell wall. While caspofungin causes cell death in yeasts and dimorphic fungi such as Candida albicans, its effect on Aspergillus fumigatus is less well understood. We used the fluorescent dyes 5,(6)-carboxyfluorescein diacetate (CFDA) and bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC), which stain live and dead cells, respectively, to further characterize the antifungal activity of caspofungin. For comparison, compounds whose mode of action was either fungistatic (fluconazole, itraconazole) or fungicidal (amphotericin B) were also evaluated. A correlation between caspofungin-induced loss of viability, decreased CFDA staining, and increased DiBAC staining was established first with C. albicans. For A. fumigatus, caspofungin caused similar dye-staining changes, which were quantified by fluorimetric analysis of stained hyphae grown in a medium that promoted dispersed growth. The minimum concentration of caspofungin required to produce these changes also decreased the level of growth-dependent reduction of the indicator dye Alamar Blue. We observed a differential effect of caspofungin as a function of cell position: 88% of apical cells and 61% of subapical branching cells failed to stain with the viable dye CFDA, but only 24% of subapical cells were unstained. Complementary results were seen with germlings from DiBAC-stained, caspofungin-treated cultures. Extended incubation of A. fumigatus with a single dose of caspofungin affected the same proportion of apical and subapical branching cells for up to 72 h. The dye-staining patterns illustrate that the cells at the active centers for new cell wall synthesis within A. fumigatus hyphae are killed when they are exposed to caspofungin.     

Antifungal Activity of Tioconazole (UK-20,349), a New Imidazole Derivative

Tioconazole (UK-20,349), a new antifungal imidazole derivative, was compared with miconazole for activity in vitro against Candida spp., Torulopsis glabrata, Cryptococcus neoformans, Aspergillus spp., and dermatophyte fungi (Trichophyton spp. and Microsporum spp.). Tioconazole was more active than miconazole against all the fungal species examined except Aspergillus, against which both agents showed similar activity. Both tioconazole and miconazole inhibited the growth of all fungi examined at concentrations well below their quoted minimum inhibitory concentrations. Their activity against fungi in vivo was investigated in mice infected systemically with Candida albicans. Both agents significantly reduced the numbers of viable Candida cells recoverable from the kidneys of infected animals, with tioconazole producing a generally more marked reduction. After administration of a single oral dose (25 mg/kg) to beagle dogs or white mice, higher and more sustained circulating levels of bioactive drug were detectable of tioconazole than of miconazole. These observations suggest that tioconazole may have potential in the treatment of both superficial and systemic mycoses in humans.     

Enhanced fungicidal activity of N-chlorotaurine in nasal secretion

The antifungal activity of N-chlorotaurine (NCT), a long-lived oxidant produced by stimulated human leucocytes, was investigated. Incubation of Aspergillus spp., Candida spp., Fusarium spp., Penicillium spp. and Alternaria spp. in 1% NCT (55 mM) for 1-4 h produced a log10 reduction in cfu of between 1 and 4. In samples of nasal secretion, killing was significantly hastened (30 min), which may be explained by the formation of monochloramine by halogenation of ammonium, which was found at a concentration of 1 mM in these samples. For these reasons, NCT is of interest as a new agent for treatment of local inflammatory mycosis, e.g. eosinophilic fungal rhinosinusitis.     

侵袭性深部真菌感染45例临床和病原学分析

目的了解本院深部真菌感染的发病状况、病原菌特性及对常用抗真菌药的敏感度，为临床深部真菌感染的治疗药物选用提供依据。方法回顾性分析我院2004年1月1日12月31日血、无菌体腔液真菌培养阳性患者的病史，并对收集的病原菌进行体外药敏测定。结果根据诊断标准，确诊为深部真菌感染患者45例。其中社区获得性深部真菌感染22例，医院深部真菌感染23例。社区获得性深部真菌感染的部位以中枢神经系统最常见，共21例，占95．5％；其次为下呼吸道感染1例。医院深部真菌感染最常见的部位为血流感染，共15例，占65．2％；其次为中枢神经系统感染5例；下呼吸道感染2例；腹腔感染2例。社区获得性感染最常见的病原菌为新型隐球菌，共17株，占77．3％；其次为白念珠菌4株；烟曲霉1株。医院感染最常见的病原菌为白念珠菌，共8株；其次为其他念珠菌属。医院感染可能与住院天数较长、高龄、大手术、长时间应用广谱抗生素、深静脉置管等因素有关。结论我院2004年深部真菌感染确诊病例中，医院感染以白念珠菌所致的血流感染最常见；社区获得性感染以隐球菌性脑膜炎最多见。氟康唑仍是治疗敏感念珠菌属尤其是白念珠菌感染的有效药物。