五倍子鞣质提取物对白假丝酵母的抗菌活性研究

目的 研究五倍子鞣质提取物对白假丝酵母的体外抗茵活性.方法 通过超声波提取五倍子有效成分鞣质,福林-酚比色法检测鞣质含量,采用微量稀释法检测五倍子鞣质提取物对白假丝酵母的最低抑菌浓度(MIC)和最低杀菌浓度(MFC),以最低抑茵浓度药物作用白假丝酵母6、12、24h,通过普通光学显微镜直接观察白假丝酵母形态结构的变化,并用吖啶橙/溴化乙锭染色,通过荧光显微镜观察白假丝酵母的死亡方式.结果 五倍子鞣质提取物对白假丝酵母的最低抑菌浓度为10.76 mg/mL,最低杀菌浓度为21.52mg/mL;五倍子鞣质提取物可导致白假丝酵母细胞变形,形态结构改变,最终导致其死亡;同时抑制细胞发芽和假菌丝的形成.结论 五倍子鞣质提取物对白假丝酵母有抑制和杀灭作用.     

Antibacterial and antifungal compounds. VIII. Synthesis and antifungal activity of pyrrol derivatives similar to trichostatin A

Some p-methylbenzolpyrrole acrylic acids and related compounds were synthesized. The new pyrrole derivatives have structural features in common with trichostatin A, an antifungal antibiotic. The above acids and derivatives were tested against Candida albicans and Candida sp in comparison with miconazole, pyrrolnitrin and amphotericin B and showed very weak antifungal activities. Occasionally some activity was found against a few strains of Candida albicans and against Candida pseudotropicalis.     

Synthesis and antimicrobial activity of some new 4-hydroxy-2H- 1,4-benzoxazin-3(4H)-ones

Some 4-hydroxy-2H-1,4-benzoxazin-3(4H)-ones were synthesized and evaluated for their antimicrobial activities against Staphylococcus aureus, Escherichia coli and Candida albicans. Compounds 9, and 10 exhibited the best activity against Candida albicans.     

Differential effects of the combination of caspofungin and terbinafine against Candida albicans, Candida dubliniensis and Candida kefyr

The activity of caspofungin (CSP) combined with terbinafine (TRB) against Candida dubliniensis, Candida kefyr and azole-resistant Candida albicans was evaluated in vitro by checkerboard analysis. The combination of CSP with TRB resulted in positive interactive effects in vitro against C. albicans and C. kefyr but not against C. dubliniensis. Moreover, true synergism was observed only against TRB resistant strains which became susceptible to this drug in the presence of CSP. In contrast, indifference was observed against strains that were already sensitive to TRB indicating that CSP may inhibit resistance to TRB.     

氟康唑协同土槿皮甲酸抗白念珠菌活性研究

摘要：目的 研究体外土槿皮甲酸(PAA)与氟康唑(FLC)联合应用对白念珠菌的抗菌活性。方法 采用微量稀释法和棋盘 微量稀释法测定PAA与FLC单独应用及联合应用于对临床分离的22株白念珠菌的最低抑菌浓度(MIC),并以部分抑菌浓度指数 (FICI)判断两药联合抑菌效应,以CAR3和CA10为目标菌株,采用时间-杀菌曲线动态监测两药体外抑菌效果。结果 PAA单独 作用于白念珠菌时,无论是对FLC耐药菌株还是对FLC敏感菌株,均呈现较好的抑菌效果,其中位MIC范围为4~16μg/mL。当 PAA与FLC联用对抗耐药白念珠菌时,可将FLC的单用浓度范围从256~512μg/mL降至为1~2μg/mL。根据FICI测定,11株对FLC 耐药菌株FICI介于0.039~0.253之间,均表现出协同抑菌作用;而11株对FLC敏感菌株,仅有2株(18.2%)FICI范围为0.312~0.375, 呈现出协同抑菌作用,剩余9株(81.8%)FICI介于0.625~1.125之间,两种药物呈现出无关作用。时间-杀菌曲线也证实,与氟康唑 单用相比,PAA与FLC联用24h后,CAR3、CA10菌株的lgCFU/mL分别下降了2.22个单位和1.57个单位,耐药菌株表现出协同作 用,而敏感菌株表现出无关作用。结论 PAA对白念珠菌表现出较好的抑菌效力,与低浓度FLC联用对耐药白念珠菌具有体外 协同抑菌作用,能显著提高FLC对耐药白念珠菌的抗菌活性。     

Regulation of Candida albicans morphogenesis by tumor necrosis factor-alpha and potential for treatment of oral candidiasis

BACKGROUND: Endogenous tumor necrosis factor-alpha (TNF-alpha) has a beneficial effect as an activation mediator of host defense against infection by the fungus Candida albicans (C. albicans). However, it is unclear whether exogenous TNF-alpha has a beneficial or detrimental effect against Candida. MATERIALS AND METHODS: The direct effect of TNF-alpha on CO2-induced morphological transformation of C. albicans blastoconidia was examined in vitro and the effect of TNF-alpha was determined in a mouse model of oral candidiasis. RESULTS: TNF-alpha suppressed hyphal formation from C. albicans blastoconidia directly and dose-dependently, whereas it did not affect the fungal budding rate at concentrations ranging from 0.01 to 10 microg/ml. In vivo, the oral administration of TNF-alpha significantly reduced the C. albicans CFU in tongue tissues of treated mice. Histopathologically, there was a decrease in the number and size of C. albicans fungi in the tongue tissues. CONCLUSION: Since orally administered TNF-alpha suppressed fungal burden in the tongue tissue without significant detrimental effects, TNF-alpha has potential as a therapeutic agent against Candida.     

In vitro activity of micafungin combined with itraconazole against Candida spp

The in vitro activity of the combination micafungin + itraconazole was evaluated against 105 strains of six species of Candida. The highest percentage of synergy was obtained against Candida albicans (50%) and the lowest against Candida tropicalis (0%).     

1-{2-[(4-取代苯基)甲氧基]-2-(取代苯基)乙基}-1H-氮唑类化合物的合成及抗真菌活性

根据氮唑类抗真菌化合物的构效关系和作用机理,设计合成了29个1-{2-[(4-取代苯基)甲氧基]-2-(取代苯基)乙基}-1H-氮唑类化合物,其中九个为首次报道。初步体外抑菌试验结果表明,大多数目标化合物对八种试验菌株都有不同程度的抗真菌活性。化合物14对白念珠菌的活性与克霉唑及益康唑相当,对其它七种试验菌株的活性明显强于克霉唑及益康唑。化合物4,12对白念珠菌活性差,对其它七种试验菌株的活性也强于克霉唑和益康唑。化合物5,6和23除对白念珠菌外,对其它七种试验菌株,也有较强活性。     

FR901469, a novel antifungal antibiotic from an unidentified fungus No.11243. II. In vitro and in vivo activities

FR901469 is a water-soluble macrocyclic lipopeptidolactone (C71H116N14O23) that has inhibitory activity against 1,3-beta-glucan synthase and exhibits in vitro and in vivo antifungal activity against both Candida albicans and Aspergillus fumigatus. The MICs of FR901469 against Candida albicans FP633 and Aspergillus fumigatus FP1305 in a micro-broth dilution test were 0.63 and 0.16 microg/ml, respectively. FR901469 showed excellent efficacy by subcutaneous injection against both Candida albicans and Aspergillus fumigatus in a murine systemic infection mode, with ED50s of 0.32 and 0.2 mg/kg, respectively. This compound also showed potent anti-Pneumocystis activity in the nude mice model with experimental Pneumocystis pneumonia. The hemolytic activity of FR901469 towards mouse red blood cells, is about 30-fold weaker than that of amphotericin B.     

Screening of plants used by North American indians for antifungal,bactericidal, larvicidal and molluscicidal activities

Nineteen plant species from fourteen families used in the traditional medicine of North American Indians have been tested for their fungicidal (Cladosporium cucumerinum, Candida albicans), bactericidal (Bacillus subtilis, Escherichia coli), larvicidal (Aedes aegypti) and molluscicidal (Biomphalaria glabrata) activities. Of the species investigated, 9 were active against Cladosporium cucumerinum, 9 against Candida albicans, 12 against Bacillus subtilis, 18 against Escherichia coli, 3 against Aedes aegypti, and 11 against Biomphalaria glabrata.     

Screening of Indonesian Plants for Antifungal and Free Radical Scavenging Activities

A total of 204 crude extracts of Indonesian plants (77 species from 43 families) have been screened for their fungicidal (Cladosporium cucumerinum, Candida albicans) and free radical scavenging [2,2-diphenyl-1-picrylhydrazyl (DPPH) radical] activities. Of the species investigated, 20 were active against Cladosporium cucumerinum, nine against Candida albicans and 24 exhibited radical scavenging properties.     

Synthesis and antimicrobial activity of some new benzimidazole carboxylates and carboxamides.

Some benzimidazole carboxylates and carboxamides were synthesized and evaluated for their antimicrobial activities against Staphylococcus aureus, Escherichia coli and Candida albicans. Among the investigated compounds 2d exhibited best activity against C. albicans.     

卡泊芬净对生物膜态白色念珠菌体外抑菌作用的试验研究

目的:检测卡泊芬净对生物膜态白色念珠菌分离株的抑菌作用,探讨临床治疗其相关感染的最适治疗剂量。方法:分别测定卡泊芬净对10株白色念珠菌临床株游离态及生物膜态的半数抑菌浓度(MIC50),并对比观察不同浓度卡泊芬净作用下白色念珠菌的增殖活性。结果:卡泊芬净对游离态白色念珠菌的MIC50为0.125～0.5mg.L-1,对生物膜态白色念珠菌的MIC50为0.25～256mg.L-1,当卡泊芬净浓度高于白色念珠菌MIC50时,全部游离态白色念珠菌的增殖活性几乎完全受到抑制,但有7株生物膜态白色念珠菌的增殖活性再次增强,且大于阳性对照的50%。结论:卡泊芬净对生物膜态白色念珠菌有抑菌作用,但并不呈浓度依赖性,当其用于治疗生物膜态白色念珠菌相关感染时的最适治疗剂量有待临床研究验证。     

PF1163A and B, new antifungal antibiotics produced by Penicillium sp. I. Taxonomy of producing strain, fermentation, isolation and biological activities

Two novel antifungal antibiotics, PF1163A and B, were isolated from the fermentation broth of Penicillium sp. They were purified from the solid cultures of rice media using ethyl acetate extraction, silica gel and Sephadex LH-20 column chromatographies. PF1163A and B showed potent growth inhibitory activity against pathogenic fungal strain Candida albicans but did not show cytotoxic activity against mammalian cells. These compounds inhibited the ergosterol biosynthesis in Candida albicans.     

Antimycotic 2-alkyldithio, 2-aralkyldithio, 2-aryldithiobenzamides

Some 2-alkyldithio, 2-aralkyldithio, 2-aryldithio benzoic acids, their methyl esters and N-monosubstituted amides were prepared and tested in vitro against Candida albicans and Trichophyton mentagrophytes. Some N-monosubstituted amides displayed activities similar to those of clotrimazole and pyrrolnitrin. Against Candida albicans, N-monosubstituted amides exhibited a generally higher activity than the corresponding N-monosubstituted amides of 2,2'-dicarboxydiphenyldisulfide.     

氨基丁酸联合卡泊芬净的体外抗白色假丝酵母菌协同作用研究

目的探讨氨基丁酸联合卡泊芬净体外抗白色假丝酵母菌的协同作用。方法采用CLSI公布的M27-A方案微量棋盘液基稀释法测定氨基丁酸单用以及联合卡泊芬净对白色假丝酵母菌标准株SC5314的MIC80值和FICI值。采用抗真菌试管敏感性实验,考察给药24h后,卡泊芬净单用以及氨基丁酸联合卡泊芬净对白色假丝酵母菌SC5314生长的影响。采用生长曲线实验,测定氨基丁酸联合卡泊芬净抗白色假丝酵母菌SC5314的生长曲线。结果氨基丁酸单用对白色假丝酵母菌SC5314的MIC80>20μmol·L-1,说明氨基丁酸单用对SC5314没有抑菌作用;但1.25μmol·L-1氨基丁酸与卡泊芬净合用的FICI<0.5,说明氨基丁酸与卡泊芬净合用表现出协同关系。另外,在抗真菌试管敏感性实验中,1.25μmol·L-1的氨基丁酸联合0.012 5μg·mL-1的卡泊芬净与0.012 5μg·mL-1的卡泊芬净单用组相比,可以直观地观察到试管内浑浊程度明显减弱,SC5314的生长受到抑制。在生长曲线实验中,1.25μmol·L-1氨基丁酸联合0.012 5μg·mL-1卡泊芬净的生长曲线显著低于同浓度下两药单用的生长曲线(P<0.05)。结论氨基丁酸本身对白色假丝酵母菌标准株SC5314没有抑菌作用,但氨基丁酸能显著增强卡泊芬净对白色假丝酵母菌SC5314的杀菌作用。     

妊娠中晚期妇女阴道假丝酵母菌病病原学特点

目的 了解天津市中心妇产科医院门诊中晚期妊娠妇女外阴阴道假丝酵母菌病(vulvovaginal candidiasis ,VVC) 的致病菌种及病原学特点。方法 对2007 年7月15日至2008年1 月30日天津市中心妇产科医院产科门诊294例有症状的中晚期妊娠妇女进行VVC 发病情况调查和常规实验室检查,并对病原体进行分类及体外抗真菌药物敏感试验。结果 294例患者中,真菌培养阳性196例（66.67 %）。悬滴法阳性率67.35%（132/196）,涂片法阳性率72.69%（143/196）,差异无统计学意义（P＞0.05）。白色假丝酵母菌感染率为95.41%（187/196）,非白色假丝酵母菌为4.59%（9/196）。悬滴法检出白色假丝酵母菌131例（70.05%）,涂片法检出137例（73.26%）,差异无统计学意义（P＞0.05）。悬滴法检出非白色假丝酵母菌1例（11.11%）,涂片法检出6例（66.67%）,差异无统计学意义（P＞0.05）。白色假丝酵母菌对常用抗真菌药物有不同程度的耐药,160例对特比萘芬耐药率。非白色假丝酵母菌对克霉唑的耐药率为66.67%（6/9）,而白色假丝酵母菌对克霉唑的耐药率仅为2.67%（5/187）,差异显著（P＜0.01）。结论 白色假丝酵母菌是妊娠中晚期VVC的主要致病菌,涂片法检出率较高。白色假丝酵母菌对常用抗真菌药物存在不同程度的耐药现象,非白色假丝酵母菌对克霉唑的耐药率高于白色假丝酵母菌。     

聚乙烯亚胺单独及与三种抗菌药物联用对白念珠菌的体外抗菌活性

目的评估多支链的阳离子高分子聚合物——聚乙烯亚胺(PEI)单独及与三种不同类别的常规抗菌药物(两性霉素B、氟康唑和多黏菌素B)联合使用对白念珠菌(MY7245和MY7238)的两种临床分离物的抗真菌活性。方法通过体外实验测定不同分子质量聚乙烯亚胺单独及与三种不同类别的常规抗菌药物联合使用对两株白念珠菌的最小抑菌浓度和杀灭时间,确定PEI单独及联合使用的体外抗真菌活性。结果分子量在2～745ku范围内的PEI均对这两种白念珠菌产生很好的抗真菌活性,且分子量小的PEI比分子量大的PEI的抗菌作用更显著。与单独作用的PEI相比,分子量较大的PEI与常规药物联合使用时可产生较强的协同作用。在体外致死研究实验中可以看到,PEI-两性霉素B和PEI-氟康唑结合物可以提高抑菌作用,但PEI-多黏菌素B结合物却拮抗抑菌作用。结论PEI单独与联合使用均对白念珠菌产生很好的抗菌效果。     

大蒜素联合氟康唑对假丝酵母体外抗菌活性的影响

目的 研究大蒜素与氟康唑体外联合应用对临床分离假丝酵母联合抗菌效应的影响。方法 采用棋盘法设计，微量稀释法测定不同浓度组合的大蒜素及大蒜素和氟康唑联合应用分别对65 株假丝酵母的最低抑菌浓度，并计算FIC 指数，判定联合抗菌效应；用10% 的小牛血清-RPMI1640 培养基诱导菌丝形成，检测大蒜素与氟康唑联合应用对假丝酵母芽管率和菌丝形成的影响。结果 大蒜素与氟康唑联合对假丝酵母的敏感菌株和耐药菌株的MIC50 均降低，较单用氟康唑和大蒜素分别降低8 倍和5 倍( 分别为由64μg/mL 降至0.25μg/mL、由32μg/mL 降至2μg/mL)；FIC 指数分布：FIC ≤ 0.5 占100%，表现为协同作用；大蒜素能加强氟康唑抑制菌丝的形成。结论 大蒜素与氟康唑联用后，对假丝酵母表现为协同抗菌作用，能显著提高氟康唑对假丝酵母的杀菌活性。     

In vitro activity of terpenes against Candida biofilms

The antibiofilm activity of 10 terpenes was tested in vitro against three Candida species by 24-h treatment of biofilms aged 1-5 days. Treatment of 24-h-old Candida albicans biofilms with carvacrol, geraniol or thymol (0.06%) resulted in >80% inhibition. Carvacrol (0.03%) inhibition was > or =75% independent of the age of the C. albicans biofilm. Carvacrol (0.125%) inhibition was >75% against Candida glabrata and Candida parapsilosis biofilms. Geraniol (> or =0.125%) and thymol (0.06% or 0.125%) inhibition was >75% against C. parapsilosis biofilms whatever their age. This study demonstrates the antibiofilm activity of terpenes and points out the exceptional efficiency of carvacrol, geraniol and thymol, which could represent candidates in the treatment of candidiasis associated with medical devices.