曲古菌素A对三唑类药物体外抗白念珠菌活性的增效作用及机制研究
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摘要
第一部分曲古菌素A对唑类药物体外抗白念珠菌活性增效作用的研究
第一章曲古菌素A对唑类药物体外抗白念珠菌等常见病原真菌活性的影响
目的选择敏感性不同的白念珠菌菌株、组蛋白去乙酰化酶基因缺失株及其它常见病原酵母菌和丝状真菌,研究曲古菌素A对氟康唑、伊曲康唑和伏立康唑抗白念珠菌等常见病原真菌的活性是否有增效作用。方法微量稀释法检测0.25μg/m1曲古菌素A与氟康唑、伊曲康唑和伏立康唑分别合用时对白念珠菌敏感株、耐药株和常见病原真菌的最低抑菌浓度,并检测白念珠菌的最小杀菌浓度,检测组蛋白去乙酰化酶编码基因缺失株HDA1△和RPD3△对三种唑类药物的体外敏感性。结果0.25μg/ml曲古菌素A与氟康唑、伊曲康唑和伏立康唑合用可不同程度地减少白念珠菌的拖尾现象,或表现为生长孔菌量减少,少数菌株的24h最低抑菌浓度降低,对最小杀菌浓度无明显影响；曲古菌素A不影响其它常见病原酵母菌和丝状真菌与唑类药物的体外敏感性；与同源株比较,HDA1△和RPD3△,体外敏感性增加。结论曲古菌素A对唑类抗真菌药物体外抗白念珠菌活性有增效作用,对其体外杀菌作用无影响。曲古菌素A与唑类抗真菌药物合用对除白念珠菌外的常见病原酵母菌和丝状真菌的体外敏感性无增效作用。组蛋白去乙酰化酶编码基因HDA1和RPD3可能与白念珠菌体外敏感性相关。
第二章曲古菌素A对唑类药物体外增效作用的机制初探
目的研究白念珠菌组蛋白去乙酰化酶编码基因的表达水平,以及组蛋白去乙酰化酶编码基因和外排泵基因在体内外获得性耐药形成过程中表达水平的变化。应用罗丹明123(Rh123)检测曲古菌素A对白念珠菌外排泵功能的影响。方法体外诱导白念珠菌对氟康唑耐药,收集药物作用前的白念珠菌和氟康唑环境下的体内外获得性耐药的白念珠菌。Trizol法提取白念珠菌RNA,白念珠菌ACT1作为内参基因,荧光定量RT-PCR检测白念珠菌临床株组蛋白去乙酰化酶编码基因HDA1、RPD3、 Hos1、HOS2、HOS3的表达水平,以及组蛋白去乙酰化酶编码基因和外排泵基因CDR1、CDR2、MDR1和FLU1在体内外获得性耐药形成过程中表达水平的变化。应用荧光染料Rh123处理白念珠菌,荧光分光光度计检测白念珠菌临床株、体外诱导耐药菌株在曲古菌素A作用下的荧光变化,以检验白念珠菌外排泵功能的变化。结果药物作用前,白念珠菌的组蛋白去乙酰化酶编码基因有不同程度表达,与菌株自身敏感性和曲古菌素A对菌株的增效作用无关；体内外获得性耐药形成过程中HDA1、RPD3、HOS1、HOS2和HOS3表达水平有不同程度增高,外排泵基因CDR1、CDR2、MDR1表达水平呈不同程度增加,LU1表达水平变化不明显。曲古菌素A对白念珠菌临床株短时间作用后,外排泵功能无明显变化,氟康唑／曲古菌素A诱导组的Rh123荧光值高于氟康唑诱导组的Rh123荧光值。结论组蛋白去乙酰化修饰可能是白念珠菌外排泵基因水平变化的上游机制之一。
第二部分念珠菌对常见抗真菌药物的体外敏感性测定
第一章微量稀释法检测念珠菌对抗真菌药物敏感性的两种观察结果方法的比较
目的应用微量稀释法检测念珠菌体外抗真菌药物敏感性,比较肉眼观察和体视显微镜观察结果的一致性及优缺点。方法参考CLSI的微量稀释法M27-A3,检测203株念珠菌对4种唑类药物(咪康唑、酮康唑、益康唑、联苯苄唑)及4种非唑类药物(制霉菌素、利拉萘酯、萘替芬、特比萘芬)的体外敏感性,并同时应用肉眼和体视显微镜两种方法观察结果。结果1.唑类药物：咪康唑、酮康唑、益康唑和联苯苄唑的一致性范围为：87.68%～96.06%；2.非唑类药物：制霉菌素、利拉萘酯、萘替芬、特比萘芬的一致性范围为91.63%～99.51%。3.与肉眼观察比较,体视显微镜观察结果具有以下优点：成像有立体感；可以观察到肉眼看不见的微量菌生长；易于区分待测菌和污染菌生长；4.除利拉萘酯、萘替芬和联苯苄唑外,咪康唑、酮康唑等均对念珠菌有良好的体外抑菌作用。结论对于微量稀释法体外检测念珠菌的抗真菌药物敏感性,应用体视显微镜可以辅助观察结果,且与肉眼读取结果有较好一致性,两种方法结合有助于体外抗真菌药物敏感性结果的判断。
第二章卢立康唑及其它6种咪唑类抗真菌药物对常见念珠菌的体外活性检测
目的评价卢立康唑及其它6种咪唑类药物对临床分离常见念珠菌的体外敏感性。方法参考CLSI的微量稀释法M27-A3方案,检测5种共183株临床分离念珠菌对卢立康唑、酮康唑、咪康唑、益康唑、克霉唑、舍他康唑、联苯苄唑7种咪唑类药物的体外敏感性。结果酮康唑、咪康唑、益康唑、克霉唑、舍他康唑和联苯苄唑的体外最低抑菌浓度范围(几何均数)分别为0.03-8(0.067)μg/ml、0.03-16(0.071)μg/ml、0.03-8(0.207)μg/ml、0.03-8(0.061)μg/ml、0.03-16(0.187)μg/ml.和0.03～>16(1.050)μg/ml。抗真菌新药卢立康唑对5种念珠菌均有较好的体外敏感性,最低抑菌浓度范围0.03～8μg/ml,几何均数为0.087μg/ml, MIC50和MIC90分别为0.06μg/ml和0.5μg/ml。包括卢立康唑在内,各受试药物均有部分菌株相对不敏感。结论除联苯苄唑外,卢立康唑等其它6种咪唑类药物均对念珠菌有良好的体外抗菌活性,但存在少数菌株相对不敏感。
Part1In vitro study of enhance effect of trichostatin A on azoles againgst Candida albicans
Chapter1In vitro study of the effect of trichostatin A on the activities of azoles against Candida albicans and other common pathogenic fungi
Objective To choose Candida albicans strains of different susceptibilities, histone deacetylases mutant strains and other common pathogenic fungi, investigate the effect of trichostatin A on the in vitro activity of azoles against these pathogenic fungi. Methods According to microdilution method, test the in vitro susceptibility of0.25μg/ml trichostatin A combination with fluconazole, itraconazole, and voriconazole against Candida albicans susceptible strains, resistant strains and other common pathogenic fungi. Then test the minimum fungicide concentration of Candida albicans. Investigate the in vitro activities of azoles against histone deacetylases mutant strains HDA1△and RPD3△. Results Combination of0.25μg/ml trichostatin A with fluconazole, itraconazole, and voriconazole decreased the trailing growth of Candida albicans in different levels, reduced the growth quantity of strains, lower the24h MIC of few strains. However, there was no effect on minimum fungicide concentration. Compared with the homologous strain, HDA1△and RPD3△strains showed increase of in vitro susceptibility. Trichostatin A had no effect on in vitro susceptibilities of other common pathogenic fungi. Conclusion Trichostatin A had the in vitro effect to enhance the activity of azoles against Candida albicans, no effect on minimum fungicide concentration. Trichostatin A was fall to enhance the in vitro activity of azoles against other common pathogenic fungi. Maybe the histone deacetylases encode gene HDAIand RPD3related to the in vitro susceptibility of Candida albicans.
Capter2Preliminary study on mechanism of enhance effect by trichostatin A to azoles against Candida albicans
Objective Evaluate the expression of histone deacetylase encoding gene of Candida albicans and changes of the expression of histone deacetylase encoding gene and efflux pumps encoding gene during the formation of Candida albicans acquired drug-resistance. Application Rhodamine123to investigate the influence of trichostatin A on the efflux pumps function of Candida albicans. Methods Induce Candida albicans resistance to fluconazole in vitro and collect the in vitro and in vivo acquired resistant strains. Then, extraction of Candida albicans RNA with Trizol, ACT1as internal control gene, evaluate the expression level of histone deacetylase encoding genes HDA1、RPD3、 HOS1、HOS2.HOS3by fluorescent qualitative RT-PCR. Meanwhile the expression level of histone deacetylase encoding gene and efflux pumps encoding gene CDR1、CDR2、 MDR1、FLU1of in vitro and in vivo acquired drug-resistance Candida albicans were evaluated by fluorescent qualitative RT-PCR. Treat clinical strains and the induction resistant strains with Rhodamine123, to evaluate the efflux pumps function by test fluorescence of Candida albicans cells. Results Different expression levels of histone deacetylase encoding genes were found in Candida albicans strains before fluconazole choose, which is unrelated with in vitro sensitivity and the enchance effect by trichostatin A. The expression of HDA1、RPD3、HOS1、HOS2and HOS3rising to different levels during the progress of acquired drug-resistance. The expression of efflux pump gene CDR2、MDR1increased during the progress of in vitro acquired drug-resistance. After a short time contact with0.25μg/ml trichostatin A, the efflux pumps function of Candida albicans clinical strains had no significant changes. The fluorescence of fluconazole/trichostatin A group was higher than fluconazole group. Conclusion Candida albicans histone deacetylase modification is probably one of the upstream mechanisms of the efflux pumps encoding gene expression level changing.
Part2In vitro antifungal susceptibilities of common antifungals agents against Candida species
Capter1Comparison of two methods for determining MICs of Candida species by microdilution methods
Objective To evaluate the in vitro antifungal susceptibility of Candida species by microdilution methods and compare visual method and stereo microscope method to determining the MIC(minimal inhibitory concentration) results. Methods According to CLSI M27-A3microdilution method, in vitro susceptibility of203Candida isolates to4azoles antifungals (miconazole, ketoconazole, econazole and bifonazole) and4non-azoles antifungals (nystatin, liranaftate, naftifine and terbinafine) were measured, and reading MIC results by visual method and stereo microscope method at the same time. Results1. Azoles:the agreements between two reading MIC methods range from87.68%to96.06%.2. Non-azoles:the agreements between two reading MIC methods range from91.63%to99.51%.3. Compared with visual method, the advantages of stereo microscope include:could get a stereoscopic image; easy to observe the micro fungi growth; easy to distinguish the tested strains and contamination fungi.4. Except for liranaftate, naftifine and bifonazole, other tested antifungals has perfect in vitro fungistasis to Candida species. Conclusion Application of stereo microscope could assist to read MIC results of in vitro susceptibility test by microdilution method, it also has good agreements with visual reading results during Candida species testing. Combination of two methods is helpful for the determination of MICs of in vitro susceptibility research.
Capter2In vitro activity of luliconazole and other6imidazoles antifungals to common Candida species
Objective Evaluate the in vitro activity of luliconazole and other6imidazoles antifungals to common Candida species clinical isolates. Methods According to CLSI microdilution method M27-A3, test in vitro susceptibility of5kinds of183isolates of Candida species against luliconazole, ketoconazole, miconazole, econazole, clotrimazole, sertaconazole and bifonazole. Results The results showed that the minimal inhibitory concentration (geometric mean) of ketoconazole, miconazole, econazole, clotrimazole, sertaconazole and bifonazole were0.03～8(0.067) μg/ml、0.03～16(0.071)μg/ml、0.03～8(0.207)μg/ml、0.03～8(0.061)μg/ml、0.03～16(0.187)μg/ml and0.03～>16(1.050)μg/ml respectively. Luliconazole had superior in vitro activity to5kinds of Candida species, the range of MIC (minimal inhibitory concentration) was0.03～8μg/ml, geometric mean was0.087μg/ml, MIC50and MIC90were0.06μg/ml and0.5μg/ml, respectively. Including luliconazole, there were some relatively insensitive strains of each antifungals. Conclusion Except for bifonazole, including luliconazole, other6imidazoles have excellent in vitro activity to Candida species, but there also exist some relatively insensitive strains among these antfungals.
第一章曲古菌素A对唑类药物体外抗白念珠菌等常见病原真菌活性的影响
目的选择敏感性不同的白念珠菌菌株、组蛋白去乙酰化酶基因缺失株及其它常见病原酵母菌和丝状真菌,研究曲古菌素A对氟康唑、伊曲康唑和伏立康唑抗白念珠菌等常见病原真菌的活性是否有增效作用。方法微量稀释法检测0.25μg/m1曲古菌素A与氟康唑、伊曲康唑和伏立康唑分别合用时对白念珠菌敏感株、耐药株和常见病原真菌的最低抑菌浓度,并检测白念珠菌的最小杀菌浓度,检测组蛋白去乙酰化酶编码基因缺失株HDA1△和RPD3△对三种唑类药物的体外敏感性。结果0.25μg/ml曲古菌素A与氟康唑、伊曲康唑和伏立康唑合用可不同程度地减少白念珠菌的拖尾现象,或表现为生长孔菌量减少,少数菌株的24h最低抑菌浓度降低,对最小杀菌浓度无明显影响；曲古菌素A不影响其它常见病原酵母菌和丝状真菌与唑类药物的体外敏感性；与同源株比较,HDA1△和RPD3△,体外敏感性增加。结论曲古菌素A对唑类抗真菌药物体外抗白念珠菌活性有增效作用,对其体外杀菌作用无影响。曲古菌素A与唑类抗真菌药物合用对除白念珠菌外的常见病原酵母菌和丝状真菌的体外敏感性无增效作用。组蛋白去乙酰化酶编码基因HDA1和RPD3可能与白念珠菌体外敏感性相关。
第二章曲古菌素A对唑类药物体外增效作用的机制初探
目的研究白念珠菌组蛋白去乙酰化酶编码基因的表达水平,以及组蛋白去乙酰化酶编码基因和外排泵基因在体内外获得性耐药形成过程中表达水平的变化。应用罗丹明123(Rh123)检测曲古菌素A对白念珠菌外排泵功能的影响。方法体外诱导白念珠菌对氟康唑耐药,收集药物作用前的白念珠菌和氟康唑环境下的体内外获得性耐药的白念珠菌。Trizol法提取白念珠菌RNA,白念珠菌ACT1作为内参基因,荧光定量RT-PCR检测白念珠菌临床株组蛋白去乙酰化酶编码基因HDA1、RPD3、 Hos1、HOS2、HOS3的表达水平,以及组蛋白去乙酰化酶编码基因和外排泵基因CDR1、CDR2、MDR1和FLU1在体内外获得性耐药形成过程中表达水平的变化。应用荧光染料Rh123处理白念珠菌,荧光分光光度计检测白念珠菌临床株、体外诱导耐药菌株在曲古菌素A作用下的荧光变化,以检验白念珠菌外排泵功能的变化。结果药物作用前,白念珠菌的组蛋白去乙酰化酶编码基因有不同程度表达,与菌株自身敏感性和曲古菌素A对菌株的增效作用无关；体内外获得性耐药形成过程中HDA1、RPD3、HOS1、HOS2和HOS3表达水平有不同程度增高,外排泵基因CDR1、CDR2、MDR1表达水平呈不同程度增加,LU1表达水平变化不明显。曲古菌素A对白念珠菌临床株短时间作用后,外排泵功能无明显变化,氟康唑／曲古菌素A诱导组的Rh123荧光值高于氟康唑诱导组的Rh123荧光值。结论组蛋白去乙酰化修饰可能是白念珠菌外排泵基因水平变化的上游机制之一。
第二部分念珠菌对常见抗真菌药物的体外敏感性测定
第一章微量稀释法检测念珠菌对抗真菌药物敏感性的两种观察结果方法的比较
目的应用微量稀释法检测念珠菌体外抗真菌药物敏感性,比较肉眼观察和体视显微镜观察结果的一致性及优缺点。方法参考CLSI的微量稀释法M27-A3,检测203株念珠菌对4种唑类药物(咪康唑、酮康唑、益康唑、联苯苄唑)及4种非唑类药物(制霉菌素、利拉萘酯、萘替芬、特比萘芬)的体外敏感性,并同时应用肉眼和体视显微镜两种方法观察结果。结果1.唑类药物：咪康唑、酮康唑、益康唑和联苯苄唑的一致性范围为：87.68%～96.06%；2.非唑类药物：制霉菌素、利拉萘酯、萘替芬、特比萘芬的一致性范围为91.63%～99.51%。3.与肉眼观察比较,体视显微镜观察结果具有以下优点：成像有立体感；可以观察到肉眼看不见的微量菌生长；易于区分待测菌和污染菌生长；4.除利拉萘酯、萘替芬和联苯苄唑外,咪康唑、酮康唑等均对念珠菌有良好的体外抑菌作用。结论对于微量稀释法体外检测念珠菌的抗真菌药物敏感性,应用体视显微镜可以辅助观察结果,且与肉眼读取结果有较好一致性,两种方法结合有助于体外抗真菌药物敏感性结果的判断。
第二章卢立康唑及其它6种咪唑类抗真菌药物对常见念珠菌的体外活性检测
目的评价卢立康唑及其它6种咪唑类药物对临床分离常见念珠菌的体外敏感性。方法参考CLSI的微量稀释法M27-A3方案,检测5种共183株临床分离念珠菌对卢立康唑、酮康唑、咪康唑、益康唑、克霉唑、舍他康唑、联苯苄唑7种咪唑类药物的体外敏感性。结果酮康唑、咪康唑、益康唑、克霉唑、舍他康唑和联苯苄唑的体外最低抑菌浓度范围(几何均数)分别为0.03-8(0.067)μg/ml、0.03-16(0.071)μg/ml、0.03-8(0.207)μg/ml、0.03-8(0.061)μg/ml、0.03-16(0.187)μg/ml.和0.03～>16(1.050)μg/ml。抗真菌新药卢立康唑对5种念珠菌均有较好的体外敏感性,最低抑菌浓度范围0.03～8μg/ml,几何均数为0.087μg/ml, MIC50和MIC90分别为0.06μg/ml和0.5μg/ml。包括卢立康唑在内,各受试药物均有部分菌株相对不敏感。结论除联苯苄唑外,卢立康唑等其它6种咪唑类药物均对念珠菌有良好的体外抗菌活性,但存在少数菌株相对不敏感。
Part1In vitro study of enhance effect of trichostatin A on azoles againgst Candida albicans
Chapter1In vitro study of the effect of trichostatin A on the activities of azoles against Candida albicans and other common pathogenic fungi
Objective To choose Candida albicans strains of different susceptibilities, histone deacetylases mutant strains and other common pathogenic fungi, investigate the effect of trichostatin A on the in vitro activity of azoles against these pathogenic fungi. Methods According to microdilution method, test the in vitro susceptibility of0.25μg/ml trichostatin A combination with fluconazole, itraconazole, and voriconazole against Candida albicans susceptible strains, resistant strains and other common pathogenic fungi. Then test the minimum fungicide concentration of Candida albicans. Investigate the in vitro activities of azoles against histone deacetylases mutant strains HDA1△and RPD3△. Results Combination of0.25μg/ml trichostatin A with fluconazole, itraconazole, and voriconazole decreased the trailing growth of Candida albicans in different levels, reduced the growth quantity of strains, lower the24h MIC of few strains. However, there was no effect on minimum fungicide concentration. Compared with the homologous strain, HDA1△and RPD3△strains showed increase of in vitro susceptibility. Trichostatin A had no effect on in vitro susceptibilities of other common pathogenic fungi. Conclusion Trichostatin A had the in vitro effect to enhance the activity of azoles against Candida albicans, no effect on minimum fungicide concentration. Trichostatin A was fall to enhance the in vitro activity of azoles against other common pathogenic fungi. Maybe the histone deacetylases encode gene HDAIand RPD3related to the in vitro susceptibility of Candida albicans.
Capter2Preliminary study on mechanism of enhance effect by trichostatin A to azoles against Candida albicans
Objective Evaluate the expression of histone deacetylase encoding gene of Candida albicans and changes of the expression of histone deacetylase encoding gene and efflux pumps encoding gene during the formation of Candida albicans acquired drug-resistance. Application Rhodamine123to investigate the influence of trichostatin A on the efflux pumps function of Candida albicans. Methods Induce Candida albicans resistance to fluconazole in vitro and collect the in vitro and in vivo acquired resistant strains. Then, extraction of Candida albicans RNA with Trizol, ACT1as internal control gene, evaluate the expression level of histone deacetylase encoding genes HDA1、RPD3、 HOS1、HOS2.HOS3by fluorescent qualitative RT-PCR. Meanwhile the expression level of histone deacetylase encoding gene and efflux pumps encoding gene CDR1、CDR2、 MDR1、FLU1of in vitro and in vivo acquired drug-resistance Candida albicans were evaluated by fluorescent qualitative RT-PCR. Treat clinical strains and the induction resistant strains with Rhodamine123, to evaluate the efflux pumps function by test fluorescence of Candida albicans cells. Results Different expression levels of histone deacetylase encoding genes were found in Candida albicans strains before fluconazole choose, which is unrelated with in vitro sensitivity and the enchance effect by trichostatin A. The expression of HDA1、RPD3、HOS1、HOS2and HOS3rising to different levels during the progress of acquired drug-resistance. The expression of efflux pump gene CDR2、MDR1increased during the progress of in vitro acquired drug-resistance. After a short time contact with0.25μg/ml trichostatin A, the efflux pumps function of Candida albicans clinical strains had no significant changes. The fluorescence of fluconazole/trichostatin A group was higher than fluconazole group. Conclusion Candida albicans histone deacetylase modification is probably one of the upstream mechanisms of the efflux pumps encoding gene expression level changing.
Part2In vitro antifungal susceptibilities of common antifungals agents against Candida species
Capter1Comparison of two methods for determining MICs of Candida species by microdilution methods
Objective To evaluate the in vitro antifungal susceptibility of Candida species by microdilution methods and compare visual method and stereo microscope method to determining the MIC(minimal inhibitory concentration) results. Methods According to CLSI M27-A3microdilution method, in vitro susceptibility of203Candida isolates to4azoles antifungals (miconazole, ketoconazole, econazole and bifonazole) and4non-azoles antifungals (nystatin, liranaftate, naftifine and terbinafine) were measured, and reading MIC results by visual method and stereo microscope method at the same time. Results1. Azoles:the agreements between two reading MIC methods range from87.68%to96.06%.2. Non-azoles:the agreements between two reading MIC methods range from91.63%to99.51%.3. Compared with visual method, the advantages of stereo microscope include:could get a stereoscopic image; easy to observe the micro fungi growth; easy to distinguish the tested strains and contamination fungi.4. Except for liranaftate, naftifine and bifonazole, other tested antifungals has perfect in vitro fungistasis to Candida species. Conclusion Application of stereo microscope could assist to read MIC results of in vitro susceptibility test by microdilution method, it also has good agreements with visual reading results during Candida species testing. Combination of two methods is helpful for the determination of MICs of in vitro susceptibility research.
Capter2In vitro activity of luliconazole and other6imidazoles antifungals to common Candida species
Objective Evaluate the in vitro activity of luliconazole and other6imidazoles antifungals to common Candida species clinical isolates. Methods According to CLSI microdilution method M27-A3, test in vitro susceptibility of5kinds of183isolates of Candida species against luliconazole, ketoconazole, miconazole, econazole, clotrimazole, sertaconazole and bifonazole. Results The results showed that the minimal inhibitory concentration (geometric mean) of ketoconazole, miconazole, econazole, clotrimazole, sertaconazole and bifonazole were0.03～8(0.067) μg/ml、0.03～16(0.071)μg/ml、0.03～8(0.207)μg/ml、0.03～8(0.061)μg/ml、0.03～16(0.187)μg/ml and0.03～>16(1.050)μg/ml respectively. Luliconazole had superior in vitro activity to5kinds of Candida species, the range of MIC (minimal inhibitory concentration) was0.03～8μg/ml, geometric mean was0.087μg/ml, MIC50and MIC90were0.06μg/ml and0.5μg/ml, respectively. Including luliconazole, there were some relatively insensitive strains of each antifungals. Conclusion Except for bifonazole, including luliconazole, other6imidazoles have excellent in vitro activity to Candida species, but there also exist some relatively insensitive strains among these antfungals.
引文
[1]赵辩.中国临床皮肤病学[M].江苏：江苏科学技术出版社,2009：573-577.
[2]Badiee P, Alborzi A, Davarpanah MA, et al. Distributions and antifungal susceptibility of Candida species from mucosal sites in HIV positive patients[J]. Arch Iran Med,2010,13(4):282-287.
[3]Fera MT, La Camera E, De Sarro A. New triazoles and echinocandins:mode of action, in vitro activity and mechanisms of resistance [J]. Expert Rev Anti Infect Ther, 2009,7(8):981-998.
[4]Sanglard D, Coste A, Ferrari S. Antifungal drug resistance mechanisms in fungal pathogens from the perspective of transcriptional gene regulation[J]. FEMS Yeast Res,2009,9(7):1029-1050.
[5]Espinel-Ingroff A. Mechanisms of resistance to antifungal agents:Yeasts and filamentous fungi[J]. Rev Iberoam Micol,2008,25(2):101-106.
[6]Riddihough G, Zahn LM. Epigenetics.What is epigenetics? Introduction[J]. Science, 2010,330(6004):611.
[7]Bonasio R, Tu S, Reinberg D. Molecular signals of epigenetic states[J]. Science. 2010,330(6004):612-616.
[8]Kaminsky ZA, Tang T, Wang SC, et al. DNA methylation profiles in monozygotic and dizygotic twins[J]. Nat Genet,2009,41(2):240-245.
[9]Suzuki MM, Bird A. DNA methylation landscapes:provocative insights from epigenomics[J]. Nat Rev Genet,2008,9(6):465-476.
[10]Khan SN, Khan AU. Role of histone acetylation in cell physiology and diseases:An update[J]. Clin Chim Acta,2010,411(19-20):1401-1411.
[11]Beumer JH, Tawbi H. Role of histone deacetylases and their inhibitors in cancer biology and treatment[J]. Curr Clin Pharmacol,2010,5(3):196-208.
[12]Bernstein BE, Tong JK, Schreiber SL. Genomewide studies of histone deacetylase function in yeast[J]. Proc Natl Acad Sci USA,2000,97(25):13708-13713.
[13]Pfaller MA, Messer SA, Georgopapadakou N, et al. Activity of MGCD290, a Hos2 histone deacetylase inhibitor, in combination with azole antifungals against opportunistic fungal pathogens[J]. J Clin Microbiol,2009,47(12):3797-3804.
[14]Smith WL, Edlind TD. Histone deacetylase inhibitors enhance Candida albicans sensitivity to azoles and related antifungals:correlation with reduction in CDR and ERG upregulation[J]. Antimicrob Agents Chemother,2002,46(11):3532-3539.
[15]Hnisz D, Majer O, Frohner IE, et al. The Set3/Hos2 histone deacetylase complex attenuates cAMP/PKA signaling to regulate morphogenesis and virulence of Candida albicans[J]. PLoS Pathog,2010,6(5):e 1000889.
[16]Klar AJ, Srikantha T, Soll DR. A histone deacetylation inhibitor and mutant promote colony-type switching of the human pathogen Candida albicans[J]. Genetics,2001, 158(2):919-924.
[17]Nguyen MH, Yu CY. Influence of incubation time, inoculum size, and glucose concentrations on spectrophotometric endpoint determinations for amphotericin B, fluconazole, and itraconazole[J]. J Clin Microbiol,1999,37(1):141-145.
[18]Pfaller MA, Messer SA, Coffmann S. Comparison of visual and spectrophotometric methods of MIC endpoint determinations by using broth microdilution methods to test five antifungal agents, including the new triazole D0870[J]. J Clin Microbiol, 1995,33(5):1094-1097.
[19]Hui GW. Modification of the microtiter reading mirror for use in the standardized micro complement fixation test[J]. Appl Microbiol,1971,21(6):1093-1094.
[20]Pfaller MA, Messer SA, Hollis RJ, et al. Multisite reproducibility of MIC results by the Sensititre Yeast One colorimetric antifungal susceptibility panel[J]. Diagn Microbiol Infect Dis,1998,31(4):543-547.
[21]Anaissie E, Paetznick V, Bodey GP. Fluconazole susceptibility testing of Candida albicans:microtiter method that is independent of inoculum size, temperature, and time of reading[J]. Antimicrob Agents Chemother,1991,35(8):1641-1646.
[22]Espinel-Ingroff A, Barchiesi F, Cuenca-Estrella M, et al. Comparison of visual 24-hour and spectrophotometric 48-hour MICs to CLSI reference microdilution MICs of fluconazole, itraconazole, posaconazole, and voriconazole for Candida spp.: a collaborative study[J]. J Clin Microbiol,2005,43(9):4535-4540.
[23]Alp S, Sancak B, Hascelik G, et al. Influence of different susceptibility testing methods and media on determination of the relevant fluconazole minimum inhibitory concentrations for heavy trailing Candida isolates with low-high phenotype[J]. Mycoses,2010,53(6):475-480.
[24]Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard CLSI document M27-A3[S]. Clinical and Laboratory Standards Institute, Wayne, PA,2008.
[25]Clinical and Laboratory Standards Institute. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts. Third Informaitonal Supplement. CLSI Document M27-S3[S]. Clinical and Laboratory Standards Institute, Wayne, PA, 2008.
[26]Lee MK, Williams LE, Warnock DW, et al. Drug resistance genes and trailing growth in Candida albicans isolates[J]. J Antimicrob Chemother,2004, 53(2):217-224.
[27]Arthington-Skaggs BA, Lee-Yang W, Ciblak MA et al. Comparison of visual and spectrophotometric methods of broth microdilution MIC endpoint determination and evaluation of a sterol quantitation method for in vitro susceptibility testing of fluconazole and itraconazole against trailing and nontrailing Candida isolates[J]. Antimicrob Agents Chemother,2002,46:2477-2481.
[28]Coenye T, De Vos M, Vandenbosch D, et al. Factors influencing the trailing endpoint observed in Candida albicans susceptibility testing using the CLSI procedure[J]. Clin Microbiol Infect,2008,14(5):495-497.
[29]Zhang H, Gao A, Li F, et al. Mechanism of action of tetrandrine, a natural inhibitor of Candida albicans drug efflux pumps[J].Yakugaku Zasshi,2009,129(5):623-630.
[30]Sharma SV, Lee DY, Li B, et al. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations[J]. Cell,2010,141(1):69-80.
[31]Morschhauser J. Regulation of multidrug resistance in pathogenic fungi[J]. Fungal Genet Biol,2010,47(2):94-106.
[32]Mai A, Rotili D, Massa S, et al. Discovery of uracil-based histone deacetylase inhibitors able to reduce acquired antifungal resistance and trailing growth in Candida albicans[J]. Bioorg Med Chem Lett,2007,17(5):1221-1225.
[33]Canton E, Peman J, Gobernado M, et al. Synergistic activities of fluconazole and voriconazole with terbinafine against four Candida species determined by checkerboard, time-kill, and Etest methods [J]. Antimicrob Agents Chemother,2005, 49(4):1593-1596.
[34]Quan H, Cao YY, Xu Z, et al. Potent in vitro synergism of fluconazole and berberine chloride against clinical isolates of Candida albicans resistant to fluconazole[J]. Antimicrob Agents Chemother,2006,50(3):1096-1099.
[35]Guo XL, Leng P, Yang Y, et al. Plagiochin E, a botanic-derived phenolic compound, reverses fungal resistance to fluconazole relating to the efflux pump[J].J Appl Microbiol,2008,104(3):831-838.
[36]Maesaki S, Marichal P, Hossain MA, et al. Synergic effects of tactolimus and azole antifungal agents against azole-resistant Candida albican strains[J]. J Antimicrob Chemother,1998,42(6):747-753.
[37]Liu L, Chen B, Qin S, et al. A novel histone deacetylase inhibitor Chidamide induces apoptosis of human colon cancer cells[K]. Biochem Biophys Res Commun,2010, 392(2):190-195.
[38]Montero A, Beierle JM, Olsen CA, et al. Design, synthesis, biological evaluation, and structural characterization of potent histone deacetylase inhibitors based on cyclic alpha/beta-tetrapeptide architectures [J]. J Am Chem Soc,2009, 131(8):3033-3041.
[39]Clinical Laboratory Standards Institute Reference Method for Broth Dilution Antifungal Susceptibility Testing of Conidium-Forming Filamentous Fungi: Approved Standard M38-A[S]. Clinical and Laboratory Standards Institute, Wayne, PA,2002.
[40]Simonetti G, Passariello C, Rotili D, et al. Histone deacetylase inhibitors may reduce pathogenicity and virulence in Candida albicans[J]. FEMS Yeast Res,2007, 7(8):1371-1380.
[41]Yu LH, Wei X, Ma M, et al. Possible inhibitory molecular mechanism of farnesol on the development of fluconazole resistance in Candida albicans biofilm[J]. Antimicrob Agents Chemother,2012,56(2):770-775.
[42]White TC, Pfaller MA, Rinaldi MG, et al. Stable azole drug resistance associated with a substrain of Candida albicans from an HIV-infected patient[J]. Oral Dis, 1997, Suppl 1:S102-109.
[43]虞丽华,马鸣,陈晓君等.白色念珠菌人工诱导耐药模型的建立及鉴定方法的研究[J].口腔生物医学,2011,2(2)：75-77.
[44]White TC. Increased mRNA levels of ERG16, CDR, and MDR1 correlate with increases in azole resistance in Candida albicans isolates from a patient infected with human immunodeficiency virus[J]. Antimicrob Agents Chemother,1997, 41(7):1482-1487.
[45]Lopez-Ribot JL, McAtee RK, Lee LN, et al. Distinct patterns of gene expression associated with development of fluconazole resistance in serial Candida albicans isolates from human immunodeficiency virus-infected patients with oropharyngeal candidiasis[J]. Antimicrob Agents Chemother,1998,42(11):2932-2937.
[46]Lopes da Rosa J, Kaufman PD. Chromatin-mediated Candida albicans virulence[J]. Biochim Biophys Acta,2012,1819(3-4):349-355.
[47]Hnisz D, Schwarzmuller T, Kuchler K. Transcriptional loops meet chromatin:a dual-layer network controls white-opaque switching in Candida albicans[J]. Mol Microbiol,2009,74(1):1-15.
[48]Hnisz D, Bardet AF, Nobile CJ, et al. A histone deacetylase adjusts transcription kinetics at coding sequences during Candida albicans morphogenesis[J], PLoS Genet,2012,8(12):e1003118.
[49]Srikantha T, Tsai L, Daniels K, et al. The histone deacetylase genes HDA1 and RPD3 play distinct roles in regulation of high-frequency phenotypic switching in Candida albicans[J]. J Bacteriol,2001,183(15):4614-4625.
[50]Zacchi LF, Schulz WL, Davis DA. HOS2 and HDA1 encode histone deacetylases with opposing roles in Candida albicans morphogenesis[J]. PLoS One,2010, 5(8):e12171.
[51]Tebarth B, Doedt T, Krishnamurthy S, et al. Adaptation of the Efglp morphogenetic pathway in Candida albicans by negative autoregulation and PKA-dependent repression of the EFG1 gene[J]. J Mol Biol,2003,329(5):949-962.
[52]Lyons CN, White TC. Transcriptional analyses of antifungal drug resistance in Candida albicans[J]. Antimicrob Agents Chemother,2000,44(9):2296-2303.
[53]Jain P, Akula I, Edlind T. Cyclic AMP signaling pathway modulates susceptibility of candida species and Saccharomyces cerevisiae to antifungal azoles and other sterol biosynthesis inhibitors [J]. Antimicrob Agents Chemother,2003,47(10):3195-3201.
[54]Clark FS, Parkinson T, Hitchcock CA, et al. Correlation between rhodamine 123 accumulation and azole sensitivity in Candida species:possible role for drug efflux in drug resistance [J]. Antimicrob Agents Chemother,1996,40(2):419-425.
[55]Sharma M, Manoharlal R, Shukla S, et al. Curcumin modulates efflux mediated by yeast ABC multidrug transporters and is synergistic with antifungals[J]. Antimicrob Agents Chemother,2009,53(8):3256-3265.
[56]韩旭东,张永信.主动外排系统与白念珠菌耐药关系研究[J].中华传染病杂志,2004,22(4)：229-233.
[57]乔建军,刘伟,万喆,等.米卡芬净对分离自中国的念珠菌和曲霉临床株体外抑菌活性的研究[J].中国真菌学杂志,2007,2(1)：5-9.
[58]Cuenca-Estrella M, Lee-Yang W, Ciblak MA, et al. Comparative evaluation of NCCLS M27-A and EUCAST broth microdilution procedures for antifungal susceptibility testing of candida species[J]. Antimicrob Agents Chemother,2002, 46(11):3644-3647.
[59]Meletiadis J, Mouton JW, Meis JF, et al. Comparison of spectrophotometric and visual readings of NCCLS method and evaluation of a colorimetric method based on reduction of a soluble tetrazolium salt,2,3-bis [2-methoxy-4-nitro-5-[(sulfenylamino) carbonyl]-2H-tetrazolium-hydroxide], for antifungal susceptibility testing of Aspergillus species[J]. J Clin Microbiol,2001,39(12):4256-4263.
[60]Llop C, Pujol I, Aguilar C, et al. Comparison of three methods of determining MICs for filamentous fungi using different end point criteria and incubation periods [J]. Antimicrob Agents Chemother,2000,44(2):239-242.
[61]Koga H, Nanjoh Y, Makimura K, et al. In vitro antifungal activities of luliconazole, a new topical imidazole[J]. Med Mycol,2009,47(6):640-647.
[62]Watanabe S, Takahashi H, Nishikawa T, et al. Dose-finding comparative study of 2 weeks of luliconazole cream treatment for tinea pedis--comparison between three groups (1%,0.5%,0.1%) by a multi-center randomised double-blind study[J]. Mycoses,2007,50(1):35-40.
[63]Watanabe S, Takahashi H, Nishikawa T, et al. A comparative clinical study between 2 weeks of luliconazole 1% cream treatment and 4 weeks of bifonazole 1% cream treatment for tinea pedis[J]. Mycoses,2006,49(3):236-241.
[64]中华医学会皮肤性病学分会.门诊就诊患者足部真菌感染的调查[J].中华皮肤科杂志,2002,35(5)：404-405.
[65]Uchida K, Tanaka T, Yamaguchi H. Achievement of complete mycological cure by topical antifungal agent NND-502 in guinea pig model of tinea pedis[J]. Microbiol Immunol,2003,47(2):143-146.
[66]Niwano Y, Kuzuhara N, Goto Y, et al. Efficacy of NND-502, a novel imidazole antimycotic agent, in experimental models of Candida albicans and Aspergillus fumigatus infections [J]. Int J Antimicrob Agents,1999,12(3):221-228.
[67]Uchida K, Nishiyama Y, Tanaka T, et al. In vitro activity of novel imidazole antifungal agent NND-502 against Malassezia species[J]. Int J Antimicrob Agents, 2003,21(3):234-238.
[68]Koga H, Tsuji Y, Inoue K, et al. In vitro antifungal activity of luliconazole against clinical isolates from patients with dermatomycoses[J]. J Infect Chemother,2006, 12(3):163-165.
[69]Uchida K, Nishiyama Y, Yamaguchi H. In vitro antifungal activity of luliconazole (NND-502), a novel imidazole antifungal agent[J]. J Infect Chemother,2004, 10(4):216-219.
[70]Ghannoum MA, Long L, Kim HG, et al. Efficacy of terbinafine compared to lanoconazole and luliconazole in the topical treatment of dermatophytosis in a guinea pig model[J]. Med Mycol,2010,48(3):491-497.
[71]Carrillo-Munoz AJ, Torres-Rodriguez JM. In-vitro antifungal activity of sertaconazole, econazole, and bifonazole against Candida spp[J], J Antimicrob Chemother,1995,36(4):713-716.
[1]Khan SN, Khan AU. Role of histone acetylation in cell physiology and diseases:An update[J]. Clin Chim Acta,2010,411(19-20):1401-1411.
[2]Wagner JM, Hackanson B, Lubbert M, et al. Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy[J]. Clin Epigenetics,2010,1(3-4):117-136.
[3]谢华峰,陆涛.抗肿瘤药物组蛋白去乙酰化酶抑制剂的研究进展(上)[J].中国药师,2010,13(6)：805-807.
[4]谢华峰,陆涛.抗肿瘤药物组蛋白去乙酰化酶抑制剂的研究进展(下)[J].中国药师,2010,13(6)：808-810.
[5]Yang XJ, Seto E. The Rpd3/Hdal family of lysine deacetylases:from bacteria and yeast to mice and men[J]. Nat Rev Mol Cell Biol,2008,9(3):206-218.
[6]Liu L, Chen B, Qin S, et al. A novel histone deacetylase inhibitor Chidamide induces apoptosis of human colon cancer cells[J]. Biochem Biophys Res Commun,2010, 392(2):190-195.
[7]Bernstein BE, Tong JK, Schreiber SL. Genomewide studies of histone deacetylase function inyeast[J]. Proc Natl Acad Sci USA,2000,97(25):13708-13713.
[8]Lopes da Rosa J, Kaufman PD. Chromatin-mediated Candida albicans virulence[J].Biochim Biophys Acta,2012,1819(3-4):349-355.
[9]Hnisz D, Majer O, Frohner IE, et al. The Set3/Hos2 histone deacetylase complex attenuates cAMP/PKA signaling to regulate morphogenesis and virulence of Candida albicans[J]. PLoS Pathog,2010,6(5):e1000889.
[10]Hnisz D, Schwarzmuller T, Kuchler K. Transcriptional loops meet chromatin:a dual-layer network controls white-opaque switching in Candida albicans[J]. Mol Microbiol,2009,74(1):1-15.
[11]Hnisz D, Bardet AF, Nobile CJ, et al. A histone deacetylase adjusts transcription kinetics at coding sequences during Candida albicans morphogenesis[J]. PLoS Genet,2012,8(12):e1003118.
[12]Klar AJ, Srikantha T, Soll DR. A histone deacetylation inhibitor and mutant promote colony-type switching of the human pathogen Candida albicans[J]. Genetics,2001, 158(2):919-924.
[13]Srikantha T, Tsai L, Daniels K, et al. The histone deacetylase genes HDA1 and RPD3 play distinct roles in regulation of high-frequency phenotypic switching in Candida albicans[J]. J Bacteriol,2001,183(15):4614-4625.
[14]Zacchi LF, Schulz WL, Davis DA. HOS2 and HDA1 encode histone deacetylases with opposing roles in Candida albicans morphogenesis [J]. PLoS One,2010, 5(8):e12171.
[15]Simonetti G, Passariello C, Rotili D, et al. Histone deacetylase inhibitors may reduce pathogenicity and virulence in Candida albicans[J]. FEMS Yeast Res,2007, 7(8):1371-1380.
[16]Tebarth B, Doedt T, Krishnamurthy S, et al. Adaptation of the Efglp morphogenetic pathway in Candida albicans by negative autoregulation and PKA-dependent repression of the EFG1 gene[J]. J Mol Biol,2003,329(5):949-962.
[17]Mai A, Rotili D, Massa S, et al. Discovery of uracil-based histone deacetylase inhibitors able to reduce acquired antifungal resistance and trailing growth in Candida albicans[J]. Bioorg Med Chem Lett,2007,17(5):1221-1225.
[18]Pfaller MA, Messer SA, Georgopapadakou N, Martell LA, Besterman JM, Diekema DJ. Activity of MGCD290, a Hos2 histone deacetylase inhibitor, in combination with azole antifungals against opportunistic fungal pathogens [J]. J Clin Microbiol, 2009,47(12):3797-3804.
[19]Smith WL, Edlind TD. Histone deacetylase inhibitors enhance Candida albicans sensitivity to azoles and related antifungals:correlation with reduction in CDR and ERG upregulation[J]. Antimicrob Agents Chemother,2002,46(11):3532-3539.
[20]Tribus M, Bauer I, Galehr J, et al. A novel motif in fungal class 1 histone deacetylases is essential for growth and development of Aspergillus[J]. Mol Biol Cell,2010,21(2):345-353.
[1]Laupland KB, Gregson DB, Church DL, et al. Invasive Candida species infections:a 5 year population-based assessment[J]. J Antimicrob Chemother,2005, 56(3):532-537.
[2]Lin JJ, Wu CT, Hsia SH, et al. Pneumocephalus:a rare presentation of Candida sphenoid sinusitis[J]. Pediatr Neurol,2009,40(5):398-400.
[3]Guillen Fiel G, Gonzalez-Granado LI, Mosqueda R, et al. Arthritis caused by Candida in an immunocompetent infant with a history of systemic candidiasis in the neonatal period[J]. An Pediatr (Bare),2009,70(4):383-385.
[4]Leibowitz JM, Montone KT, Basu D. Warthin tumor presenting as a fungal abscess in an immunocompetent host:case report and review of the literature[J]. Head Neck, 2010,32(1):133-136.
[5]Lima R, Shams W, Kalra S, et al. Candida glabrata liver abscess and fungemia complicating severe calculus cholecystitis in an immunocompetent nondiabetic host[J]. South Med J,2010,103(3):245-247.
[6]Enache-Angoulvant A, Torti F, Tassart M, et al. Candidal abscess of the parotid gland due to Candida glabrata:report of a case and literature review[J]. Med Mycol, 2010,48(2):402-405.
[7]Safdar A, Bannister TW, Safdar Z. The predictors of outcome in immunocompetent patients with hematogenous candidiasis [J]. Int J Infect Dis,2004,8(3):180-186.
[8]Lee CH, Oh JM, Oh SR, et al. Candida Arthritis after Arthroscopic Arthroplasty in a Patient without Predisposing Factors[J]. Open Rheumatol J,2010,11;4:7-9.
[9]Matthew R. Lammi, Darilyn Moyer. Candida krusei Lung Abscess in an Immunocompetent Man[J]. Infect Dis Clin Pract,2009,17(1):58-60.
[10]M Jimenez-Palop, M Corteguera, R Ibanez, et al. Olecranon bursitis due to Candida parapsilosis in an immunocompetent adult[J]. Ann Rheum Dis,2002,61:279-281.
[11]Sanguinetti M, Posteraro B, Fiori B, et al. Mechanisms of azole resistance in clinical isolates of Candida glabrata collected during a hospital survey of antifungal resistance[J]. Antimicrob Agents Chemother,2005,49(2):668-679.
[12]Kothavade RJ, Kura MM, Valand AG, et al. Candida tropicalis:its prevalence, pathogenicity and increasing resistance to fluconazole[J]. J Med Microbiol,2010, 59(Pt 8):873-880.
[13]Henry LR, Packer MD, Brennan J. Airway-obstructing laryngeal candidiasis in an immunocompetent host[J]. Otolaryngol Head Neck Surg,2005,133(5):808-810.
[14]Nunes FP, Bishop T, Prasad ML, et al. Laryngeal candidiasis mimicking malignancy[J]. Laryngoscope,2008,118(11):1957-1959.
[15]Kobayashi T, Miyazaki Y, Yanagihara K, et al. A probable case of aspiration pneumonia caused by Candida glabrata in a non-neutropenic patient with candidemia[J]. Intern Med,2005,44(11):1191-1194.
[16]Hsu HH, Chang YL, Chen JS, et al. An esophageal mass with coexistent Mycobacterium chelonae and Candida albicans infections in an immunocompetent adult[J]. J Infect,2006,52(3):e77-79.
[17]Hasosah MY, Showail M, Al-Sahafi A, et al. Esophageal candidiasis in an immunocompetent girl[J]. World J Pediatr,2009,5(2):152-154.
[18]Hong XY, Chou YC, Lazareff JA. Brain stem candidiasis mimicking cerebellopontine angle tumor[J]. Surg Neurol,2008,70(1):87-91.
[19]Vardakas KZ, Michalopoulos A, Kiriakidou KG, et al. Candidaemia:incidence, risk factors, characteristics and outcomes in immunocompetent critically ill patients[J]. Clin Microbiol Infect,2009,15(3):289-292.
[20]Carra Dalliere C, Thouvenot E, Baptista G, et al. Meningomyeloradiculitis in an immunocompetent patient[J]. Rev Neurol (Paris),2010,166(8-9):741-744.
[21]Posteraro B, Tumbarello M, La Sorda M, et al. Azole resistance of Candida glabrata in a case of recurrent fungemia[J]. J Clin Microbiol,2006,44(8):3046-3047.
[22]Barth T, Broscheit J, Bussen S, et al. Maternal sepsis and intrauterine fetal death resulting from Candida tropicalis chorioamnionitis in a woman with a retained intrauterine contraceptive device[J]. Acta Obstet Gynecol Scand,2002, 81(10):981-982.
[23]Rath S, Kar S, Sahu SK, et al. Fungal periorbital necrotizing fasciitis in an immunocompetent adult[J]. Ophthal Plast Reconstr Surg,2009,25(4):334-335.
[24]Lezrek M, Nadah M, El Moussaif H, et al. Postoperative Candida Iris nodules:report of a case[J]. Bull Soc Belge Ophtalmol,2009, (313):45-48.
[25]Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis:2009 update by the Infectious Diseases Society of America[J]. Clin Infect Dis,2009,48(5):503-535.
[2]Badiee P, Alborzi A, Davarpanah MA, et al. Distributions and antifungal susceptibility of Candida species from mucosal sites in HIV positive patients[J]. Arch Iran Med,2010,13(4):282-287.
[3]Fera MT, La Camera E, De Sarro A. New triazoles and echinocandins:mode of action, in vitro activity and mechanisms of resistance [J]. Expert Rev Anti Infect Ther, 2009,7(8):981-998.
[4]Sanglard D, Coste A, Ferrari S. Antifungal drug resistance mechanisms in fungal pathogens from the perspective of transcriptional gene regulation[J]. FEMS Yeast Res,2009,9(7):1029-1050.
[5]Espinel-Ingroff A. Mechanisms of resistance to antifungal agents:Yeasts and filamentous fungi[J]. Rev Iberoam Micol,2008,25(2):101-106.
[6]Riddihough G, Zahn LM. Epigenetics.What is epigenetics? Introduction[J]. Science, 2010,330(6004):611.
[7]Bonasio R, Tu S, Reinberg D. Molecular signals of epigenetic states[J]. Science. 2010,330(6004):612-616.
[8]Kaminsky ZA, Tang T, Wang SC, et al. DNA methylation profiles in monozygotic and dizygotic twins[J]. Nat Genet,2009,41(2):240-245.
[9]Suzuki MM, Bird A. DNA methylation landscapes:provocative insights from epigenomics[J]. Nat Rev Genet,2008,9(6):465-476.
[10]Khan SN, Khan AU. Role of histone acetylation in cell physiology and diseases:An update[J]. Clin Chim Acta,2010,411(19-20):1401-1411.
[11]Beumer JH, Tawbi H. Role of histone deacetylases and their inhibitors in cancer biology and treatment[J]. Curr Clin Pharmacol,2010,5(3):196-208.
[12]Bernstein BE, Tong JK, Schreiber SL. Genomewide studies of histone deacetylase function in yeast[J]. Proc Natl Acad Sci USA,2000,97(25):13708-13713.
[13]Pfaller MA, Messer SA, Georgopapadakou N, et al. Activity of MGCD290, a Hos2 histone deacetylase inhibitor, in combination with azole antifungals against opportunistic fungal pathogens[J]. J Clin Microbiol,2009,47(12):3797-3804.
[14]Smith WL, Edlind TD. Histone deacetylase inhibitors enhance Candida albicans sensitivity to azoles and related antifungals:correlation with reduction in CDR and ERG upregulation[J]. Antimicrob Agents Chemother,2002,46(11):3532-3539.
[15]Hnisz D, Majer O, Frohner IE, et al. The Set3/Hos2 histone deacetylase complex attenuates cAMP/PKA signaling to regulate morphogenesis and virulence of Candida albicans[J]. PLoS Pathog,2010,6(5):e 1000889.
[16]Klar AJ, Srikantha T, Soll DR. A histone deacetylation inhibitor and mutant promote colony-type switching of the human pathogen Candida albicans[J]. Genetics,2001, 158(2):919-924.
[17]Nguyen MH, Yu CY. Influence of incubation time, inoculum size, and glucose concentrations on spectrophotometric endpoint determinations for amphotericin B, fluconazole, and itraconazole[J]. J Clin Microbiol,1999,37(1):141-145.
[18]Pfaller MA, Messer SA, Coffmann S. Comparison of visual and spectrophotometric methods of MIC endpoint determinations by using broth microdilution methods to test five antifungal agents, including the new triazole D0870[J]. J Clin Microbiol, 1995,33(5):1094-1097.
[19]Hui GW. Modification of the microtiter reading mirror for use in the standardized micro complement fixation test[J]. Appl Microbiol,1971,21(6):1093-1094.
[20]Pfaller MA, Messer SA, Hollis RJ, et al. Multisite reproducibility of MIC results by the Sensititre Yeast One colorimetric antifungal susceptibility panel[J]. Diagn Microbiol Infect Dis,1998,31(4):543-547.
[21]Anaissie E, Paetznick V, Bodey GP. Fluconazole susceptibility testing of Candida albicans:microtiter method that is independent of inoculum size, temperature, and time of reading[J]. Antimicrob Agents Chemother,1991,35(8):1641-1646.
[22]Espinel-Ingroff A, Barchiesi F, Cuenca-Estrella M, et al. Comparison of visual 24-hour and spectrophotometric 48-hour MICs to CLSI reference microdilution MICs of fluconazole, itraconazole, posaconazole, and voriconazole for Candida spp.: a collaborative study[J]. J Clin Microbiol,2005,43(9):4535-4540.
[23]Alp S, Sancak B, Hascelik G, et al. Influence of different susceptibility testing methods and media on determination of the relevant fluconazole minimum inhibitory concentrations for heavy trailing Candida isolates with low-high phenotype[J]. Mycoses,2010,53(6):475-480.
[24]Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard CLSI document M27-A3[S]. Clinical and Laboratory Standards Institute, Wayne, PA,2008.
[25]Clinical and Laboratory Standards Institute. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts. Third Informaitonal Supplement. CLSI Document M27-S3[S]. Clinical and Laboratory Standards Institute, Wayne, PA, 2008.
[26]Lee MK, Williams LE, Warnock DW, et al. Drug resistance genes and trailing growth in Candida albicans isolates[J]. J Antimicrob Chemother,2004, 53(2):217-224.
[27]Arthington-Skaggs BA, Lee-Yang W, Ciblak MA et al. Comparison of visual and spectrophotometric methods of broth microdilution MIC endpoint determination and evaluation of a sterol quantitation method for in vitro susceptibility testing of fluconazole and itraconazole against trailing and nontrailing Candida isolates[J]. Antimicrob Agents Chemother,2002,46:2477-2481.
[28]Coenye T, De Vos M, Vandenbosch D, et al. Factors influencing the trailing endpoint observed in Candida albicans susceptibility testing using the CLSI procedure[J]. Clin Microbiol Infect,2008,14(5):495-497.
[29]Zhang H, Gao A, Li F, et al. Mechanism of action of tetrandrine, a natural inhibitor of Candida albicans drug efflux pumps[J].Yakugaku Zasshi,2009,129(5):623-630.
[30]Sharma SV, Lee DY, Li B, et al. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations[J]. Cell,2010,141(1):69-80.
[31]Morschhauser J. Regulation of multidrug resistance in pathogenic fungi[J]. Fungal Genet Biol,2010,47(2):94-106.
[32]Mai A, Rotili D, Massa S, et al. Discovery of uracil-based histone deacetylase inhibitors able to reduce acquired antifungal resistance and trailing growth in Candida albicans[J]. Bioorg Med Chem Lett,2007,17(5):1221-1225.
[33]Canton E, Peman J, Gobernado M, et al. Synergistic activities of fluconazole and voriconazole with terbinafine against four Candida species determined by checkerboard, time-kill, and Etest methods [J]. Antimicrob Agents Chemother,2005, 49(4):1593-1596.
[34]Quan H, Cao YY, Xu Z, et al. Potent in vitro synergism of fluconazole and berberine chloride against clinical isolates of Candida albicans resistant to fluconazole[J]. Antimicrob Agents Chemother,2006,50(3):1096-1099.
[35]Guo XL, Leng P, Yang Y, et al. Plagiochin E, a botanic-derived phenolic compound, reverses fungal resistance to fluconazole relating to the efflux pump[J].J Appl Microbiol,2008,104(3):831-838.
[36]Maesaki S, Marichal P, Hossain MA, et al. Synergic effects of tactolimus and azole antifungal agents against azole-resistant Candida albican strains[J]. J Antimicrob Chemother,1998,42(6):747-753.
[37]Liu L, Chen B, Qin S, et al. A novel histone deacetylase inhibitor Chidamide induces apoptosis of human colon cancer cells[K]. Biochem Biophys Res Commun,2010, 392(2):190-195.
[38]Montero A, Beierle JM, Olsen CA, et al. Design, synthesis, biological evaluation, and structural characterization of potent histone deacetylase inhibitors based on cyclic alpha/beta-tetrapeptide architectures [J]. J Am Chem Soc,2009, 131(8):3033-3041.
[39]Clinical Laboratory Standards Institute Reference Method for Broth Dilution Antifungal Susceptibility Testing of Conidium-Forming Filamentous Fungi: Approved Standard M38-A[S]. Clinical and Laboratory Standards Institute, Wayne, PA,2002.
[40]Simonetti G, Passariello C, Rotili D, et al. Histone deacetylase inhibitors may reduce pathogenicity and virulence in Candida albicans[J]. FEMS Yeast Res,2007, 7(8):1371-1380.
[41]Yu LH, Wei X, Ma M, et al. Possible inhibitory molecular mechanism of farnesol on the development of fluconazole resistance in Candida albicans biofilm[J]. Antimicrob Agents Chemother,2012,56(2):770-775.
[42]White TC, Pfaller MA, Rinaldi MG, et al. Stable azole drug resistance associated with a substrain of Candida albicans from an HIV-infected patient[J]. Oral Dis, 1997, Suppl 1:S102-109.
[43]虞丽华,马鸣,陈晓君等.白色念珠菌人工诱导耐药模型的建立及鉴定方法的研究[J].口腔生物医学,2011,2(2)：75-77.
[44]White TC. Increased mRNA levels of ERG16, CDR, and MDR1 correlate with increases in azole resistance in Candida albicans isolates from a patient infected with human immunodeficiency virus[J]. Antimicrob Agents Chemother,1997, 41(7):1482-1487.
[45]Lopez-Ribot JL, McAtee RK, Lee LN, et al. Distinct patterns of gene expression associated with development of fluconazole resistance in serial Candida albicans isolates from human immunodeficiency virus-infected patients with oropharyngeal candidiasis[J]. Antimicrob Agents Chemother,1998,42(11):2932-2937.
[46]Lopes da Rosa J, Kaufman PD. Chromatin-mediated Candida albicans virulence[J]. Biochim Biophys Acta,2012,1819(3-4):349-355.
[47]Hnisz D, Schwarzmuller T, Kuchler K. Transcriptional loops meet chromatin:a dual-layer network controls white-opaque switching in Candida albicans[J]. Mol Microbiol,2009,74(1):1-15.
[48]Hnisz D, Bardet AF, Nobile CJ, et al. A histone deacetylase adjusts transcription kinetics at coding sequences during Candida albicans morphogenesis[J], PLoS Genet,2012,8(12):e1003118.
[49]Srikantha T, Tsai L, Daniels K, et al. The histone deacetylase genes HDA1 and RPD3 play distinct roles in regulation of high-frequency phenotypic switching in Candida albicans[J]. J Bacteriol,2001,183(15):4614-4625.
[50]Zacchi LF, Schulz WL, Davis DA. HOS2 and HDA1 encode histone deacetylases with opposing roles in Candida albicans morphogenesis[J]. PLoS One,2010, 5(8):e12171.
[51]Tebarth B, Doedt T, Krishnamurthy S, et al. Adaptation of the Efglp morphogenetic pathway in Candida albicans by negative autoregulation and PKA-dependent repression of the EFG1 gene[J]. J Mol Biol,2003,329(5):949-962.
[52]Lyons CN, White TC. Transcriptional analyses of antifungal drug resistance in Candida albicans[J]. Antimicrob Agents Chemother,2000,44(9):2296-2303.
[53]Jain P, Akula I, Edlind T. Cyclic AMP signaling pathway modulates susceptibility of candida species and Saccharomyces cerevisiae to antifungal azoles and other sterol biosynthesis inhibitors [J]. Antimicrob Agents Chemother,2003,47(10):3195-3201.
[54]Clark FS, Parkinson T, Hitchcock CA, et al. Correlation between rhodamine 123 accumulation and azole sensitivity in Candida species:possible role for drug efflux in drug resistance [J]. Antimicrob Agents Chemother,1996,40(2):419-425.
[55]Sharma M, Manoharlal R, Shukla S, et al. Curcumin modulates efflux mediated by yeast ABC multidrug transporters and is synergistic with antifungals[J]. Antimicrob Agents Chemother,2009,53(8):3256-3265.
[56]韩旭东,张永信.主动外排系统与白念珠菌耐药关系研究[J].中华传染病杂志,2004,22(4)：229-233.
[57]乔建军,刘伟,万喆,等.米卡芬净对分离自中国的念珠菌和曲霉临床株体外抑菌活性的研究[J].中国真菌学杂志,2007,2(1)：5-9.
[58]Cuenca-Estrella M, Lee-Yang W, Ciblak MA, et al. Comparative evaluation of NCCLS M27-A and EUCAST broth microdilution procedures for antifungal susceptibility testing of candida species[J]. Antimicrob Agents Chemother,2002, 46(11):3644-3647.
[59]Meletiadis J, Mouton JW, Meis JF, et al. Comparison of spectrophotometric and visual readings of NCCLS method and evaluation of a colorimetric method based on reduction of a soluble tetrazolium salt,2,3-bis [2-methoxy-4-nitro-5-[(sulfenylamino) carbonyl]-2H-tetrazolium-hydroxide], for antifungal susceptibility testing of Aspergillus species[J]. J Clin Microbiol,2001,39(12):4256-4263.
[60]Llop C, Pujol I, Aguilar C, et al. Comparison of three methods of determining MICs for filamentous fungi using different end point criteria and incubation periods [J]. Antimicrob Agents Chemother,2000,44(2):239-242.
[61]Koga H, Nanjoh Y, Makimura K, et al. In vitro antifungal activities of luliconazole, a new topical imidazole[J]. Med Mycol,2009,47(6):640-647.
[62]Watanabe S, Takahashi H, Nishikawa T, et al. Dose-finding comparative study of 2 weeks of luliconazole cream treatment for tinea pedis--comparison between three groups (1%,0.5%,0.1%) by a multi-center randomised double-blind study[J]. Mycoses,2007,50(1):35-40.
[63]Watanabe S, Takahashi H, Nishikawa T, et al. A comparative clinical study between 2 weeks of luliconazole 1% cream treatment and 4 weeks of bifonazole 1% cream treatment for tinea pedis[J]. Mycoses,2006,49(3):236-241.
[64]中华医学会皮肤性病学分会.门诊就诊患者足部真菌感染的调查[J].中华皮肤科杂志,2002,35(5)：404-405.
[65]Uchida K, Tanaka T, Yamaguchi H. Achievement of complete mycological cure by topical antifungal agent NND-502 in guinea pig model of tinea pedis[J]. Microbiol Immunol,2003,47(2):143-146.
[66]Niwano Y, Kuzuhara N, Goto Y, et al. Efficacy of NND-502, a novel imidazole antimycotic agent, in experimental models of Candida albicans and Aspergillus fumigatus infections [J]. Int J Antimicrob Agents,1999,12(3):221-228.
[67]Uchida K, Nishiyama Y, Tanaka T, et al. In vitro activity of novel imidazole antifungal agent NND-502 against Malassezia species[J]. Int J Antimicrob Agents, 2003,21(3):234-238.
[68]Koga H, Tsuji Y, Inoue K, et al. In vitro antifungal activity of luliconazole against clinical isolates from patients with dermatomycoses[J]. J Infect Chemother,2006, 12(3):163-165.
[69]Uchida K, Nishiyama Y, Yamaguchi H. In vitro antifungal activity of luliconazole (NND-502), a novel imidazole antifungal agent[J]. J Infect Chemother,2004, 10(4):216-219.
[70]Ghannoum MA, Long L, Kim HG, et al. Efficacy of terbinafine compared to lanoconazole and luliconazole in the topical treatment of dermatophytosis in a guinea pig model[J]. Med Mycol,2010,48(3):491-497.
[71]Carrillo-Munoz AJ, Torres-Rodriguez JM. In-vitro antifungal activity of sertaconazole, econazole, and bifonazole against Candida spp[J], J Antimicrob Chemother,1995,36(4):713-716.
[1]Khan SN, Khan AU. Role of histone acetylation in cell physiology and diseases:An update[J]. Clin Chim Acta,2010,411(19-20):1401-1411.
[2]Wagner JM, Hackanson B, Lubbert M, et al. Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy[J]. Clin Epigenetics,2010,1(3-4):117-136.
[3]谢华峰,陆涛.抗肿瘤药物组蛋白去乙酰化酶抑制剂的研究进展(上)[J].中国药师,2010,13(6)：805-807.
[4]谢华峰,陆涛.抗肿瘤药物组蛋白去乙酰化酶抑制剂的研究进展(下)[J].中国药师,2010,13(6)：808-810.
[5]Yang XJ, Seto E. The Rpd3/Hdal family of lysine deacetylases:from bacteria and yeast to mice and men[J]. Nat Rev Mol Cell Biol,2008,9(3):206-218.
[6]Liu L, Chen B, Qin S, et al. A novel histone deacetylase inhibitor Chidamide induces apoptosis of human colon cancer cells[J]. Biochem Biophys Res Commun,2010, 392(2):190-195.
[7]Bernstein BE, Tong JK, Schreiber SL. Genomewide studies of histone deacetylase function inyeast[J]. Proc Natl Acad Sci USA,2000,97(25):13708-13713.
[8]Lopes da Rosa J, Kaufman PD. Chromatin-mediated Candida albicans virulence[J].Biochim Biophys Acta,2012,1819(3-4):349-355.
[9]Hnisz D, Majer O, Frohner IE, et al. The Set3/Hos2 histone deacetylase complex attenuates cAMP/PKA signaling to regulate morphogenesis and virulence of Candida albicans[J]. PLoS Pathog,2010,6(5):e1000889.
[10]Hnisz D, Schwarzmuller T, Kuchler K. Transcriptional loops meet chromatin:a dual-layer network controls white-opaque switching in Candida albicans[J]. Mol Microbiol,2009,74(1):1-15.
[11]Hnisz D, Bardet AF, Nobile CJ, et al. A histone deacetylase adjusts transcription kinetics at coding sequences during Candida albicans morphogenesis[J]. PLoS Genet,2012,8(12):e1003118.
[12]Klar AJ, Srikantha T, Soll DR. A histone deacetylation inhibitor and mutant promote colony-type switching of the human pathogen Candida albicans[J]. Genetics,2001, 158(2):919-924.
[13]Srikantha T, Tsai L, Daniels K, et al. The histone deacetylase genes HDA1 and RPD3 play distinct roles in regulation of high-frequency phenotypic switching in Candida albicans[J]. J Bacteriol,2001,183(15):4614-4625.
[14]Zacchi LF, Schulz WL, Davis DA. HOS2 and HDA1 encode histone deacetylases with opposing roles in Candida albicans morphogenesis [J]. PLoS One,2010, 5(8):e12171.
[15]Simonetti G, Passariello C, Rotili D, et al. Histone deacetylase inhibitors may reduce pathogenicity and virulence in Candida albicans[J]. FEMS Yeast Res,2007, 7(8):1371-1380.
[16]Tebarth B, Doedt T, Krishnamurthy S, et al. Adaptation of the Efglp morphogenetic pathway in Candida albicans by negative autoregulation and PKA-dependent repression of the EFG1 gene[J]. J Mol Biol,2003,329(5):949-962.
[17]Mai A, Rotili D, Massa S, et al. Discovery of uracil-based histone deacetylase inhibitors able to reduce acquired antifungal resistance and trailing growth in Candida albicans[J]. Bioorg Med Chem Lett,2007,17(5):1221-1225.
[18]Pfaller MA, Messer SA, Georgopapadakou N, Martell LA, Besterman JM, Diekema DJ. Activity of MGCD290, a Hos2 histone deacetylase inhibitor, in combination with azole antifungals against opportunistic fungal pathogens [J]. J Clin Microbiol, 2009,47(12):3797-3804.
[19]Smith WL, Edlind TD. Histone deacetylase inhibitors enhance Candida albicans sensitivity to azoles and related antifungals:correlation with reduction in CDR and ERG upregulation[J]. Antimicrob Agents Chemother,2002,46(11):3532-3539.
[20]Tribus M, Bauer I, Galehr J, et al. A novel motif in fungal class 1 histone deacetylases is essential for growth and development of Aspergillus[J]. Mol Biol Cell,2010,21(2):345-353.
[1]Laupland KB, Gregson DB, Church DL, et al. Invasive Candida species infections:a 5 year population-based assessment[J]. J Antimicrob Chemother,2005, 56(3):532-537.
[2]Lin JJ, Wu CT, Hsia SH, et al. Pneumocephalus:a rare presentation of Candida sphenoid sinusitis[J]. Pediatr Neurol,2009,40(5):398-400.
[3]Guillen Fiel G, Gonzalez-Granado LI, Mosqueda R, et al. Arthritis caused by Candida in an immunocompetent infant with a history of systemic candidiasis in the neonatal period[J]. An Pediatr (Bare),2009,70(4):383-385.
[4]Leibowitz JM, Montone KT, Basu D. Warthin tumor presenting as a fungal abscess in an immunocompetent host:case report and review of the literature[J]. Head Neck, 2010,32(1):133-136.
[5]Lima R, Shams W, Kalra S, et al. Candida glabrata liver abscess and fungemia complicating severe calculus cholecystitis in an immunocompetent nondiabetic host[J]. South Med J,2010,103(3):245-247.
[6]Enache-Angoulvant A, Torti F, Tassart M, et al. Candidal abscess of the parotid gland due to Candida glabrata:report of a case and literature review[J]. Med Mycol, 2010,48(2):402-405.
[7]Safdar A, Bannister TW, Safdar Z. The predictors of outcome in immunocompetent patients with hematogenous candidiasis [J]. Int J Infect Dis,2004,8(3):180-186.
[8]Lee CH, Oh JM, Oh SR, et al. Candida Arthritis after Arthroscopic Arthroplasty in a Patient without Predisposing Factors[J]. Open Rheumatol J,2010,11;4:7-9.
[9]Matthew R. Lammi, Darilyn Moyer. Candida krusei Lung Abscess in an Immunocompetent Man[J]. Infect Dis Clin Pract,2009,17(1):58-60.
[10]M Jimenez-Palop, M Corteguera, R Ibanez, et al. Olecranon bursitis due to Candida parapsilosis in an immunocompetent adult[J]. Ann Rheum Dis,2002,61:279-281.
[11]Sanguinetti M, Posteraro B, Fiori B, et al. Mechanisms of azole resistance in clinical isolates of Candida glabrata collected during a hospital survey of antifungal resistance[J]. Antimicrob Agents Chemother,2005,49(2):668-679.
[12]Kothavade RJ, Kura MM, Valand AG, et al. Candida tropicalis:its prevalence, pathogenicity and increasing resistance to fluconazole[J]. J Med Microbiol,2010, 59(Pt 8):873-880.
[13]Henry LR, Packer MD, Brennan J. Airway-obstructing laryngeal candidiasis in an immunocompetent host[J]. Otolaryngol Head Neck Surg,2005,133(5):808-810.
[14]Nunes FP, Bishop T, Prasad ML, et al. Laryngeal candidiasis mimicking malignancy[J]. Laryngoscope,2008,118(11):1957-1959.
[15]Kobayashi T, Miyazaki Y, Yanagihara K, et al. A probable case of aspiration pneumonia caused by Candida glabrata in a non-neutropenic patient with candidemia[J]. Intern Med,2005,44(11):1191-1194.
[16]Hsu HH, Chang YL, Chen JS, et al. An esophageal mass with coexistent Mycobacterium chelonae and Candida albicans infections in an immunocompetent adult[J]. J Infect,2006,52(3):e77-79.
[17]Hasosah MY, Showail M, Al-Sahafi A, et al. Esophageal candidiasis in an immunocompetent girl[J]. World J Pediatr,2009,5(2):152-154.
[18]Hong XY, Chou YC, Lazareff JA. Brain stem candidiasis mimicking cerebellopontine angle tumor[J]. Surg Neurol,2008,70(1):87-91.
[19]Vardakas KZ, Michalopoulos A, Kiriakidou KG, et al. Candidaemia:incidence, risk factors, characteristics and outcomes in immunocompetent critically ill patients[J]. Clin Microbiol Infect,2009,15(3):289-292.
[20]Carra Dalliere C, Thouvenot E, Baptista G, et al. Meningomyeloradiculitis in an immunocompetent patient[J]. Rev Neurol (Paris),2010,166(8-9):741-744.
[21]Posteraro B, Tumbarello M, La Sorda M, et al. Azole resistance of Candida glabrata in a case of recurrent fungemia[J]. J Clin Microbiol,2006,44(8):3046-3047.
[22]Barth T, Broscheit J, Bussen S, et al. Maternal sepsis and intrauterine fetal death resulting from Candida tropicalis chorioamnionitis in a woman with a retained intrauterine contraceptive device[J]. Acta Obstet Gynecol Scand,2002, 81(10):981-982.
[23]Rath S, Kar S, Sahu SK, et al. Fungal periorbital necrotizing fasciitis in an immunocompetent adult[J]. Ophthal Plast Reconstr Surg,2009,25(4):334-335.
[24]Lezrek M, Nadah M, El Moussaif H, et al. Postoperative Candida Iris nodules:report of a case[J]. Bull Soc Belge Ophtalmol,2009, (313):45-48.
[25]Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis:2009 update by the Infectious Diseases Society of America[J]. Clin Infect Dis,2009,48(5):503-535.