天津市公安特警总队特警足部红色毛癣菌体外药敏试验

目的 本课题通过对从公安特警总队特警足部浅表真菌病分离鉴定的红色毛癣菌进行药敏试验,为公安特警中足部浅表真菌病的治疗提供依据。 [方法] 以患有足部浅表真菌病的天津市区特警总队特警为研究对象,使用M38-A2方案进行红色毛癣菌抗真菌药物敏感性研究：测定氟康唑、伊曲康唑、特比萘芬对所分离的红色毛癣菌的最低抑菌浓度(MIC)。[结果] 红色毛癣菌体外抗真菌药物敏感性研究显示氟康唑、伊曲康唑和特比萘酚对红色毛癣菌MIC值具有显著性差异。[结论] 体外抗真菌药物敏感性研究显示氟康唑、伊曲康唑和特比萘酚对红色毛癣菌MIC值具有显著性差异。     

外阴阴道念珠菌对抗真菌药物的敏感性

目的 :了解外阴阴道念珠菌对抗真菌药物的敏感性 ,为临床治疗外阴阴道念珠菌病提供依据。方法 :采用API法对分离自临床外阴阴道念珠菌病患者的 12 0株念珠菌进行种间鉴定 ;参照美国国家实验室标准委员会 (NCCLS)M - 2 7A方案( 1997) ,采用微量法检测 12 0株临床试验菌株、5株参考株及 1株质量控制株对 3种抗真菌药物的敏感性。结果 :氟康唑、伊曲康唑及特比萘芬对 12 0株临床菌株的最小抑菌浓度 (MIC)均数分别为 :( 7.2± 1.9) ,( 0 .2 6± 0 .0 5 )和 ( 10 .2± 3 .6) ( μg·ml-1)。结论 :氟康唑、伊曲康唑对外阴阴道念珠菌显示较高的敏感性 ,而特比萘芬对其敏感性欠佳。     

我院2005～2006年519例真菌耐药性分析

目的:了解我院真菌感染的特点及药物敏感情况。方法:常规培养分离真菌,用VITEK全自动微生物分析仪鉴定到种,药敏试验采用Rosco抗真菌药敏纸片扩散法及NCCLSM27-A肉汤稀释法。结果:519株真菌全为酵母菌属,白色念珠菌占70.3%。制霉菌素敏感性最好,其次为两性霉素B,氟康唑、伊曲康唑敏感性不理想。结论:当前临床常用抗真菌药耐药菌株明显增多,进行真菌药敏监测势在必行。     

感染念珠菌对常用抗真菌药物的体外敏感实验

目的；了解本院内感染所分离的念珠菌流行情况以及对常用抗真菌药物的敏感性。方法：采用1997年NCCLS推荐的药敏试验方案微量稀释法检测124株临床分离的念珠菌对氟康唑、两性霉素B，伊曲康唑和酮康唑的敏感性。结果：氟康唑对念珠菌的敏感性下降(85．5％)。伊曲康唑对念珠菌的抗菌语与氟康唑类似，耐药菌株亦明显增多，敏感性为82．3％。部分菌株对氟康唑和伊曲康唑的药敏结果呈现“拖尾”现象。结论：念珠菌巳成为院内感染的常见病源菌之一，其中非白色念珠菌的比例明显升高。部分菌株对氟康唑和伊曲康唑耐药。     

特比萘芬与氟康唑或伊曲康唑体外联合抗白念珠菌的作用

目的探讨特比萘芬与氟康唑或伊曲康唑体外联合抗白念珠菌的作用。方法采用微量液体稀释法测定特比萘芬、氟康唑、伊曲康唑对生殖器部位分离的36株白念珠菌药敏试验，应用棋盘微量稀释法测定特比萘芬与氟康唑或伊曲康唑对36株白念珠菌的联合药敏试验。结果白念珠菌菌株对氟康唑、伊曲康唑、特比萘芬耐药株分别为3株（8．33％）、4株（11．11％）、6株（16．67％）。特比萘芬和氟康唑联用MIC几何平均数较其单独应用均显著降低（t=3．590，P〈0．05；t=3．252，P〈0．05），15株有协同作用（42％），18株有相加作用（50％），3株无关作用（8％）；特比萘芬和伊曲康唑联用后的MIC几何平均数较其单独应用均显著降低（t=3．849，P〈0．001；t=2．409，P〈0．05），表现为协同作用有14株（39％），相加作用的有17株（47％），无关作用的有5株（14％）；均未发现拮抗作用。结论特比萘芬与氟康唑或伊曲康唑联合应用对大部分白念珠菌能产生协同作用和相加作用，提示特比萘芬与氟康唑或伊曲康唑联合应用能增强抗白念珠菌的作用。     

不同抗真菌药治疗白念珠菌性阴道炎模型小鼠的疗效比较

目的 比较特比萘芬、氟康唑、伊曲康唑等抗真菌药治疗小鼠白念珠菌性阴道炎的疗效。方法构建ICR小鼠白念珠菌性阴道炎模型，应用特比萘芬、氟康唑、伊曲康唑灌服治疗，并在灌药后不同时间动态观察阴道灌洗液真菌载量。结果 特比萘芬组在不同时间点其小鼠阴道灌洗液真菌载量明显高于氟康唑组及伊曲康唑组（P＜0.01），连续灌药1周后其真菌载量仍处于较高水平。氟康唑组与伊曲康唑组从灌服药物后第2天开始其阴道灌洗液真菌载量明显减少，灌服药物后第3天开始阴道灌洗液真菌载量即处于极低水平，表明两组疗效显著，但两者之间疗效差异无显著性（P＞0.05）。结论 特比萘芬治疗小鼠白念珠菌性阴道炎的疗效欠佳，而氟康唑与伊曲康唑治疗小鼠白念珠菌性阴道炎疗效显著。     

3种抗真菌药治疗甲真菌病药物经济学分析

目的对伊曲康唑、特比萘芬、氟康唑3种不同抗真菌药物治疗120例甲真菌病患者的成本效果分析。方法选择120例病例,随机分为3组,分别给予伊曲康唑、特比萘芬、氟康唑治疗,观察各组疗效并运用药物经济学方法进行分析。结果3种药物均有较好的抗真菌疗效,特比萘芬疗效优于伊曲康唑及氟康唑,伊曲康唑疗效优于氟康唑。平均成本-效果比分别为8.9,8.0,11.7。结论药物经济学分析结果为特比萘芬治疗甲真菌病最优。     

NCCLS M27-A微量法测定白色念珠菌对伊曲康唑的药物敏感性

目的体外分析医院临床分离获得的致病性白色念珠菌对伊曲康唑的药物敏感性。方法采用美国国家临床实验室标准化委员会(NCCLS)推荐的M27-A方案微量法测定白色念珠菌对伊曲康唑的MIC80值,观察伊曲康唑体外抗真菌效果。结果共收集白色念珠菌33株,药敏结果敏感率显示,敏感为66.66%(22/33),剂量敏感为27.27%(9/33),耐药为6.06%(2/33)。结论部分白色念珠菌对伊曲康唑敏感性降低;M27-A微量法操作方便,准确性高,检测结果对指导临床合理用药具有重要意义。     

卡泊芬净联合伏立康唑、伊曲康唑或两性霉素B对尖端赛多孢子菌体外抑菌活性

目的 观察卡泊芬净(棘白霉素类抗真菌药)联合伏立康唑、伊曲康唑(三唑素)或两性霉素B(多烯类).作用于15株尖端赛多孢子菌的体外抑菌活性.方法 参照美国国家临床和实验室标准研究所(CLSI)的M38-A方案,药物间相互作用用分数抑菌浓度(FIC值)表示.结果 体外单独用药时,伏立康唑的MIC值的几何均数(GM)显著低于其他药物.在15株受试菌中,卡泊芬净与伊曲康唑联合时,全部菌株显示为协同作用;卡泊芬净与两性霉素B联合时,有27%的菌株显示为协同作用;卡泊芬净与伏立康唑联合时,均表现为无关作用.结论 卡泊芬净可增强伊曲康唑的体外抗真菌活性,卡泊芬净与伊曲康唑联合用药有望作为临床上治疗尖端赛多孢子菌感染的一种有效方法.     

特比萘芬治疗真菌病现状

特比萘芬是一种丙烯胺类的抗真菌药物 ,具有广谱抗真菌活性 ,临床上有口服和外用制剂。广泛用于治疗浅部真菌病 ,结果显示特比萘芬治疗浅部真菌病疗程短、疗效高、不良反应少、复发率低。尤其对甲真菌病进行短程连续疗法、冲击疗法、短程隔日疗法比较 ,以短程连续疗法疗效最好。对由皮肤癣菌引起的甲真菌病特比萘芬比灰黄霉素、伊曲康唑和氟康唑疗效要好。除此之外 ,特比萘芬还有效治疗了一些曲霉病、孢子丝菌病和着色芽生菌病。     

比较国产与进口伏立康唑注射剂的体外抗真菌活性

目的观察血清和溶媒对伏立康唑(抗真菌药)注射制剂体外抑菌活性的影响。方法国产与进口伏立康唑注射液分别用专用溶媒和蒸馏水溶解,参照美国临床和实验室标准化研究所(CLSI)的微量液基稀释法,测定并比较2种制剂的体外抗真菌活性。在培养基中加入人血清(10%),比较2者抗真菌活性的差异。受试菌株包括114株念珠菌,20株新生隐球菌,10株阿萨希毛孢子菌,62株曲霉,10镰刀菌以及10株尖端赛多孢子菌。结果在体外,2种制剂的溶媒对常见致病真菌的抗真菌活性无明显差异;在有血清存在的条件下,2种制剂的抗真菌活性一致。结论国产与进口伏立康唑的体外抗真菌活性无明显差异。     

Neo-Sensitab纸片扩散法与NCCL SM27-A微量稀释法测定97株酵母对抗真菌药物敏感性的比较

目的比较Neo-Sensitab纸片扩散法和NCCLS微量稀释法的一致性,评价该商品化方案的稳定性。方法同时采用NCCLSM27-A微量稀释法和Neo-Sensitab纸片扩散法测定临床分离的97株酵母对两性霉素B(AMB)、氟康唑(FCZ)、5-氟胞嘧啶(5-FC)、酮康唑(KCZ)和伊曲康唑(ITC)等五种常用抗真菌药物的敏感性。结果两种方法的药敏结果一致率分别为AMB100%,FCZ94.8%,5-FC93.8%,KCZ75.3%和ITC84.5%。结论纸片扩散法和微量稀释法药敏测试结果一致率较高,以FCZ、AMB和5-FC最佳,该方法检测敏感株的准确率较高,而在区分耐药株和中介株方面有所不足。     

Antifungal susceptibility testing of yeasts: uses and limitations

With recent developments in the field of mycology, such as increased incidence of fungal infections, the introduction of newer, safer antifungals, and the emergence of resistance, the need for clinically relevant antifungal susceptibility testing methods is obvious. Studies performed over the past decade have allowed the National Committee for Clinical Laboratory Standards Subcommittee on Antifungal Testing to achieve consensus on a new standardized broth dilution method for in vitro susceptibility testing of yeasts (NCCLS M27-A). Once the reproducibility of the M27-A document was established, tentative breakpoints for fluconazole and itraconazole were derived. The availability of a standardized procedure for determining the minimum inhibitory concentrations (MICs) of antifungal agents is an important tool in drug discovery and development. In addition, it provides means for detection of resistant strains and, in the case of oropharyngeal candidiasis, means for patient management.     

Update on Clinical Antifungal Susceptibility Testing for Candida Species

With the emergence of fungi as important nosocomial pathogens, increasing reports of antifungal resistance, and expanding drug therapy options, the need for clinically relevant antifungal susceptibility testing is evident. Over the last decade, the National Committee for Clinical Laboratory Standards (NCCLS) worked to standardize procedures for in vitro susceptibility testing of Candida species against fluconazole, itraconazole, 5-fluorocytosine, and amphotericin B. With the establishment of a reproducible methodology, correlation of antifungal susceptibility in vitro with clinical outcome is a priority. The NCCLS proposed susceptibility breakpoints for the three agents against Candida species, with breakpoints for amphotericin B forthcoming. These breakpoints could provide useful guidance in some clinical situations involving azole or 5-fluorocytosine therapy; however, routine susceptibility testing of fungal isolates should be discouraged.     

Voriconazole activity against clinical yeast isolates: a multicentre Italian study

The activity of voriconazole was tested in vitro against 1996 clinical yeast isolates collected in 20 Italian microbiology laboratories. Voriconazole susceptibility testing was carried out with the broth microdilution (NCCLS M27-A2), Etest and disk diffusion methods. The minimum inhibitory concentrations at which 90% of the isolates were inhibited (MIC90) obtained with the NCCLS method were 0.03 mg/L for Candida albicans, 0.5 mg/L for Candida non-albicans and 0.25 mg/L for other genera; those obtained with Etesting were, respectively, 0.032 mg/L, 0.125 mg/L and 0.125 mg/L. With the disk diffusion method, the majority of isolates (92.3%) showed inhibition zone diameters between 21 mm and 40 mm. Using a tentative MIC cut-off of 1mg/L as indicative of in vitro susceptibility, 98.1% of the isolates tested in our study would be classified as susceptible, and only 28 (1.4%) of the isolates, with MICs higher than 2mg/L, would be classified as resistant to the drug. Our findings confirm the broad-spectrum in vitro activity of voriconazole against yeasts, including Candida species that are generally less susceptible to other azoles.     

In vitro antifungal and antibacterial activities of pentacycloundecane tetra-amines

The antifungal and antimicrobial activities of three pentacycloundecane (PCU) tetra-amine derivatives are reported herein. The in vitro activity of these PCU derivatives against yeasts (Candida albicans and non-albicans species) and filamentous fungi was evaluated using the Clinical and Laboratory Standards Institute (CLSI) M27-A2 and M38-A2 guidelines and the 2H-tetrazolium salt, (MTS) colorimetric method. The minimum inhibitory concentration against most of the tested clinical fungal strains for GKM8 and GKM9 derivatives ranges from 15.6 to 62.5 μg/mL while GKM11 ranged from 3.9 to 7.8 μg/mL. The GKM11 derivative was also active against fluconazole-resistant strains of fungi. The GKM11 derivative also exhibited promising activity against filamentous fungi in that it was 2.5 times more active than amphotericin B against Sporothrix schenckii. Antibacterial activity was determined using the broth microdilution method (BMM) and the iodonitrotetrazolium chloride (INT) colorimetric method. The GKM11 derivative was mainly active against Gram-positive bacteria with MIC ranging from 3.9 to 7.8 μg/mL. Activity against Gram-negative bacteria tested was limited to Escherichia coli and Elizabethkingia meningoseptica (MIC of 31 μg/mL).     

Antifungal activity of xanthones: evaluation of their effect on ergosterol biosynthesis by high-performance liquid chromatography

The increasing resistance of pathogenic fungi to antifungal compounds and the reduced number of available drugs led to the search for therapeutic alternatives among natural products, including xanthones. The antifungal activity of 27 simple oxygenated xanthones was evaluated by determination of their minimal inhibitory concentration on clinical and type strains of Candida, Cryptococcus, Aspergillus and dermatophytes, and their preponderance on the dermatophytic filamentous fungi was observed. Furthermore, a simple and efficient HPLC method with UV detection to study the effect of the active xanthones on the biosynthesis of ergosterol was developed and validated. Using this methodology, the identification and quantification of fungal sterols in whole cells of Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, and Trichophyton mentagrophytes were accomplished. In summary, 1,2-dihydroxyxanthone was found to be the most active compound against all strains tested, showing its effect on sterol biosynthesis by reducing the amount of ergosterol detected.     

海娜花抗真菌有效成分的提取工艺优化与抑菌效力研究

目的 研究海娜花抗真菌有效成分的提取工艺优化与抑菌效力。方法 分别采用回流提取法与超声提取法提取海娜花。采用高效液相色谱作定量分析,流动相A为磷酸二氢铵30 mmol/L、B为甲醇（用磷酸调pH=3）,梯度洗脱,温度为30℃,进样量为20μL,色谱柱为Agilent Zorbax SB-C18柱（250 mm×4.6 mm,5μm）。考察溶剂、温度、时间对有效成分提取效果的影响,确定最佳提取工艺。采用美国临床实验室标准化委员会（NCCLS）产孢丝状真菌抗真菌药敏试验方案M38-A,以白色念珠菌为模型菌,对海娜花提取物的抗真菌效力进行初步研究。结果与结论 回流提取法的最佳工艺条件为10倍量70%乙醇溶液,100℃下回流提取1.0 h,共提取3次。超声提取法的最佳工艺条件为10倍量70%乙醇溶液,50℃下超声提取1.5 h,共提取3次。海娜花提取物对白色念珠菌的最低抑菌浓度（MIC）为320～640μg/mL。     

In vitro antifungal activity of amorolfine, a new morpholine antimycotic agent

In vitro antifungal activities of amorolfine (MT-861), a newly developed morpholine antimycotic agent, against a wide range of pathogenic fungal strains were investigated using an agar-dilution method with an imidazole antifungal agent, clotrimazole (CTZ), as the reference drug. The results showed that MT-861 had a broad antifungal spectrum, and was active against all of the pathogenic fungi tested except nonpigmented filamentous fungi such as aspergilli and penicillia. Dermatophytes and Malassezia furfur was the most highly susceptible to MT-861. Antifungal activities of MT-861 against most strains of these fungi as well as those against most strains of dimorphic fungi were higher than those of CTZ. By contrast, MT-861 showed lower activities against pathogenic yeasts such as Candida albicans than CTZ. Several assay conditions, such as inoculum size of fungi, incubation time, media pH and compositions including serum supplementation, affected MT-861 activities against C. albicans and, to lesser extents, those against Trichophyton mentagrophytes. MIC values of MT-861 against C. albicans and other Candida spp., were the lowest on casitone agar. MT-861 exerted fungicidal actions toward susceptible fungi such as T. mentagrophytes and Sporothrix schenckii at relatively low concentrations, and these activities were increased when the time of incubation was extended beyond 24 hours after inoculation of testing organisms. Susceptibilities of any strains of C. albicans and C. glabrata to MT-861 were not reduced by as many as 15 successive transfers in MT-861 containing media.