共查询到20条相似文献,搜索用时 15 毫秒
1.
Li AP 《Chemico-biological interactions》2007,168(1):16-29
The recent developments in the isolation, culturing, and cryopreservation of human hepatocytes, and the application of the cells in drug development are reviewed. Recent advances include the improvement of cryopreservation procedures to allow cell attachment, thereby extending the use of the cells to assays that requires prolong culturing such as enzyme induction studies. Applications of human hepatocytes in drug development include the evaluation of metabolic stability, metabolite profiling and identification, drug-drug interaction potential, and hepatotoxic potential. The use of intact human hepatocytes, because of the complete, undisrupted metabolic pathways and cofactors, allows the development of data more relevant to humans in vivo than tissue fractions such as human liver microsomes. Incorporation of key in vivo factors with the intact hepatocytes in vitro may help predictive human in vivo drug properties. For instance, evaluation of drug metabolism and drug-drug interactions with intact human hepatocytes in 100% human serum may eliminate the need to determine in vivo intracellular concentrations for the extrapolation of in vitro data to in vivo. Co-culturing of hepatocytes and nonhepatic primary cells from other organs in the integrated discrete multiple organ co-culture (IdMOC) may allow the evaluation of multiple organ interactions in drug metabolism and drug toxicity. In conclusion, human hepatocytes represent a critical experimental model for drug development, allowing early evaluation of human drug properties to guide the design and selection of drug candidates with a high probability of clinical success. 相似文献
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脑膜炎败血伊丽莎白菌(Elizabethkingia meningoseptica, EM)可引起肺部感染、新生儿脑膜炎、菌血症等疾病,医院重症监护病房检出率较高,是院内感染的重要病原体之一。随着抗菌药物的广泛使用,EM对β-内酰胺类、氨基糖苷类、氟喹诺酮类等临床常用抗菌药物呈多重耐药,给临床治疗带来极大困难。目前EM的耐药机制研究主要集中于产生药物灭活酶、药物作用靶位改变、外排泵、形成生物膜等方面。EM可同时携带多个耐药基因,如GOB、BlaB、CME等,从而介导多重耐药。本文就国内外EM耐药现状、耐药机制进行综述,旨在为预防和控制EM的医院内感染提供参考。 相似文献
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The prevalence of gentamicin 2'-N-acetyltransferase in the Proteeae and its role in the O-acetylation of peptidoglycan 总被引:1,自引:0,他引:1
Abstract The prevalence of aac(2')-Ia , a gene coding for gentamicin 2'-JV-acetyltransferase in Providenda stuartii , among species of the Proteeae was investigated to determine if it is a common resistance factor and whether the correlation observed in P. stuartii between its expression and the levels of peptidoglycan O -acetylation represents a general feature of bacteria producing this form of modified peptidoglycan. An evaluation of the MICs of gentamicin for each of the species of the Proteeae did not reveal any apparent relationship between resistance and the degree of O-acetylation of peptidoglycan. The entire aac(2')-Ia gene was used as a probe in Southern hybridization experiments against genomic DNA from each species of the Proteeae. A sequence with strong homology to aac(2')-Ia was present only in Proteus penneri while weak hybridization was also observed to the restriction digested DNA from Providenda rettgeri . Other bacteria that O -acetylate peptidoglycan were also screened with this probe and a homologous DNA sequence was only found in Neisseria subflava . These data suggest that AAC(2')-Ia may contribute to the rO -acetylation of peptidoglycan in P. stuartii , but a more specific enzyme must also be produced for this function. 相似文献
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Philip James Kijak Jean Jackson Badar Shaikh 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1997,691(2):669
A method capable of separating and quantifying the three major and one minor components of gentamicin in milk has been developed. The method is capable of detecting 15 ng/ml gentamicin, based on a total of the four components. Milk samples are centrifuged at 4°C, the fat layer removed, and the samples deproteinated with 30% trichloracetic acid. After a second centrifugation, the supernatant is passed through a C18 solid-phase extraction column. The column is washed with water, water-methanol (50:50) and methanol. Ammonium hydroxide (16%) in methanol is used to elute the gentamicin. The eluent is evaporated to near dryness and taken up with water. An aliquot of the sample is then mixed with an ion-pairing reagent for chromatography. Separation is achieved using pentanesulfonic acid in a water-methanol mobile phase on a C18 reversed-phase column. The o-phthalaldehyde fluorescence derivatives of gentamicin are formed post-column and are detected with excitation at 340 nm and emission at 430 nm. The percent recovery of gentamicin averaged 72, 78 and 88% from milk samples fortified at 15, 30 and 60 ng/ml, respectively. 相似文献
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Fluorodensitometric evaluation of gentamicin from plasma and urine by high-performance thin-layer chromatography 总被引:1,自引:0,他引:1
Chhanda P Bhogte V.B Patravale Padma V Devarajan 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1997,694(2):1246
High-performance thin-layer chromatographic (HPTLC) analysis of gentamicin by in situ fluorodensitometric evaluation of its 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) derivative is presented. The aminoglycoside components separated on silica gel plates using chloroform–methanol–20% ammonium hydroxide (2.4:2.2:1.5, v/v/v) as the mobile phase were reacted with NB-Cl to yield highly fluorescent derivatives. The calibration curves of gentamicin in water, plasma and urine were linear in the range 40–200 ng. The mean values of intercept, slope and correlation coefficient were 16.82±0.473, 6.83±0.015 and 0.9968±0.0017 for standard curves in water, 17.35±0.375, 6.85±0.018 and 0.9941±0.0012 for standard curves in plasma and 14.35±0.286, 6.86±0.002 and 0.9933+0.0011 for standard curves in urine respectively. The analytical technique was validated for within-day and day-to-day variation. The results indicate that HPTLC, coupled with in situ fluorodensitometry, is a reliable and valuable technique for quantitative analysis of the bulk drug gentamicin and gentamicin from urine and plasma. 相似文献
7.
肠球菌为革兰阳性(G+)球菌,广泛分布于自然环境及人和动物消化道内,既往认为肠球菌是对人类无害的共栖菌。自20世纪80年代以来,肠球菌严重感染的发生率和病死率明显升高,肠球菌成为了院内感染的重要病原菌,不仅可引起尿路感染,皮肤软组织感染,甚至危及生命的腹腔感染、败血症、心内膜炎、脑膜炎等,在败血症中肠球菌为第三位的病原菌,仅次于凝固酶阴性葡萄球菌和金黄色葡萄球菌。由于肠球菌对多种抗菌药物具有天然耐药(固有耐药)和获得性耐药的特性,许多常用抗菌药物活性降低,往往造成临床治疗失败。为此,相研究对有关肠球菌的耐药机制的相关文献进行综述,以利于同道们进一步研究。 相似文献
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目的:探讨多重耐药鲍曼不动杆菌(MDR-Ab)的耐药性及其耐药基因,为临床合理选择抗菌药物提供依据。方法:回顾性分析2018年1月至2018年12月鲍曼不动杆菌感染的住院患者信息。使用VITEK-32微生物分析仪/梅里埃药敏卡片GN13鉴定MDR-Ab 95株。采用聚合酶链式反应(多重PCR)检测MDR-Ab携带相关耐药基因。结果:95株MDR-Ab对头孢类抗菌药物耐药率为100%。对氨苄西林-舒巴坦和头孢哌酮-舒巴坦耐药率分别为95.79%和81.05%,对美罗培南和亚胺培南耐药率分别为56.84%和57.89%,对庆大霉素和阿米卡星耐药率均为88.42%,对环丙沙星和左氧氟沙星耐药率分别为100%和88.42%,对四环素、米诺环素、替加环素耐药率分别为87.37%、16.84%和9.47%,对多粘菌素B耐药率为1.05%。95株MDR-Ab中携带β-内酰胺酶中A类酶耐药基因TEM、PER分别95株和25株,D类酶耐药基因OXA-51、carO和adeB各95株,OXA-23基因90株。携带消毒剂耐药基因qacE 60株。携带16S r RNA甲基化酶耐药基因armA 75株。每株MDR-Ab除携带TEM+carO+adeB+OXA-51四种基因外,另同时携带四种基因20株(21.05%),三种基因38株(40.00%)。结论:MDR-Ab对多种抗菌药物的耐药率较高,携带的耐药基因型主要为TEM、carO、adeB及OXA-51。携带多种耐药基因是MDR-Ab耐药重要原因。加强医院感染防控、合理应用抗菌药物对于延缓泛鲍曼不动杆菌耐药性发展具有重要的临床意义。 相似文献
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HIV抗药性的产生严重阻碍了HIV疾病的治疗进程,因此开发新的抗HIV药物以及对病毒进行抗药性分析对于提高HIV疾病的治疗效果非常重要。将利用HIV假病毒构建的抗HIV药物评价系统及病毒抗药性分析系统应用于药物筛选及耐药性分析具有常规方法无法替代的优点。介绍了目前常用的几种类型HIV假病毒的特点和构建方法,同时介绍了假病毒感染细胞的系统及其在细胞水平筛选抗HIV药物和对HIV临床分离株进行耐药性分析这两方面的应用,并通过与常规方法进行比较来分析利用假病毒技术进行研究的优势及局限性, 还通过总结大量学者的研究成果证明了利用假病毒技术进行药物筛选和抗药性分析具有准确、安全和高效的特点。 相似文献
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目的了解长沙地区临床分离金黄色葡萄球菌(以下简称金葡菌)对常用抗菌药物的耐药现状,探讨金黄色葡萄球菌对甲氧西林的耐药水平。方法收集长沙地区11家医院2009年11月至2010年11月临床分离的非重复金葡菌279株,应用Vitek-2全自动微生物分析系统进行鉴定,K-B法检测金葡菌对24种药物的敏感性,产色头孢菌素试验检测β-内酰胺酶以及D试验检测诱导型克林霉素耐药。应用头孢西丁和苯唑西林纸片扩散法筛查耐甲氧西林的金葡菌(MRSA),琼脂稀释法检测头孢西丁和苯唑西林的最低抑菌浓度(MIC)。结果在被检测的24种药物中,敏感率〉50%的药物为9种,未发现对万古霉素、替考拉宁和利奈唑胺耐药菌株;耐药率〉50%的抗菌药物有11种,其中以青霉素和氨苄西林的耐药率最高(均为97.1%)。MRSA的分离率达54.5%,且对常用的16种抗菌药物的耐药率均显著高于甲氧西林敏感金黄色葡萄球菌(MSSA)。279株金葡菌中,β-内酰胺酶阳性250株(89.6%);红霉素耐药而克林霉素敏感或中介的30株中,D试验阳性22株(73.3%)。苯唑西林(OXA)和头孢西丁(FOX)MIC范围分别为0.125~〉256μg/mL和2~〉256μg/mL,苯唑西林的MIC50和MIC90分别为128μg/mL和256μg/mL,头孢西丁的MIC50和MIC90分别为64μg/mL和256μg/mL。结论长沙地区临床分离金葡菌对常用抗菌药物呈多重耐药;MRSA不仅分离率高,而且对甲氧西林呈高水平耐药。 相似文献
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细菌药物耐受(Drug tolerance)是指在没有发生耐药突变的情况下细菌耐受抗生素杀菌的能力,表现为细菌群体难以或不能被杀菌型药物清除。细菌药物耐受的调控机制包括群体异质性和压力应答两种途径。药物耐受性的本质是细菌通过调控或遗传突变的方式改变生理代谢状态,从而抵制药物引起的细胞死亡途径。比如,处于缓慢生长或生长停滞生理状态的细菌往往能够抵抗药物的杀菌作用。临床研究发现细菌药物耐受是导致持续性感染疾病迁延难愈、复发率高的病原学机制之一。同时,研究证明耐受性的形成是细菌耐药性(Drug resistance)产生的进化途径之一。因此,揭示细菌药物耐受的机制将有助于人们深入了解抗生素的杀菌机理,以及细菌耐药性形成的适应性进化机制,并为新型杀菌药物以及药物增效剂靶标的发现和抗生素合理使用策略的开发奠定理论基础。 相似文献
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Since the introduction of antiretroviral therapy(ART),the lifespan and quality of life of patients infected with HIV have been significantly improved.But treatment efficacy was compromised eventually by the development of resistance to antiretroviral drugs,and more new anti-HIV drugs with lower toxicity and higher activity were needed.Based on the experience and lessons learned from the treatment in the developed countries,US FDA suggested that more pharmacodynamical researches should be considered ahead of the clinical trials.To facilitate the anti-HIV drug research and development,we reviewed a few specialized issues that should be focused on drug evaluations in vitro,including: 1)Mechanism of action studies,demonstrating the candidate drug's efficacy to specifically inhibit viral replication or a virus-specific function and confirm the drug target.2)Drug resistance studies,selecting the drug-resistant variants in vitro and determining the activities inhibiting HIV isolates resistant to approved antiretroviral drugs of the same class.3)Antiviral activity in vitro in the presence of serum proteins,ascertaining whether an investigational product is significantly bound by serum proteins.4)Combination activity analysis,evaluating in vitro antiviral activity of an investigational product in two-drug combinations with other drugs approved. 相似文献
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目的 检测多重耐药伤寒沙门菌对抗菌药物的敏感性及其耐药基因携带情况,为伤寒沙门菌引起的腹泻治疗提供科学依据。 方法 采用微量肉汤稀释的方法测定大连地区临床分离的78株伤寒沙门菌对12种抗生素的敏感性;用PCR方法检测TEM型β内酰胺酶基因、catA和catB氯霉素乙酰基转移酶基因以及cmlA氯霉素外排泵蛋白基因、aac(6′)Ⅰb和aac3Ⅱ型氨基糖苷类修饰酶基因、qacEΔ1sul1耐消毒剂和磺胺基因、多重耐药外排基因acrB等8种耐药基因。 结果 78株沙门菌对12种药物有不同程度耐药(1.28%~74.35%)。得到9株多重耐药菌株,其中5株检出TEM型β内酰胺酶基因;7株耐氯霉素的伤寒沙门菌菌株中,2株仅检出catA基因,1株仅检出catB基因,1株仅检出cmlA氯霉素外排泵蛋白基因,2株同时检出catA基因和cmlA氯霉素外排泵蛋白基因;2株检出aac(6′)Ⅰb基因,1株检出aac3Ⅱ型氨基糖苷类修饰酶基因;4株检出耐消毒剂和磺胺基因qacEΔ1sul1;6株检出多重耐药外排基因acrB。 结论 大连地区临床分离的伤寒沙门菌存在严峻的耐药现象,多种耐药基因存在于耐药伤寒沙门菌中,可能是导致菌株对多种抗菌药物耐药的原因。 相似文献
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目的 监测与分析医院近三年鲍曼不动杆菌分布及对常用抗菌药物的耐药性。方法 对2012-2014年门诊及住院部各科室送检标本进行分离培养,用VITEK2-Compact全自动细菌分析仪进行细菌的鉴定及药敏分析,应用SPSS 13.0软件进行数据统计分析。结果 近三年鲍曼不动杆菌共分离出2 217株,主要来源于痰液标本,占65.27%;且主要分布于重症医学科,其次是NICU及呼吸内科。2012-2014年鲍曼不动杆菌的分离率差异有统计学意义(2=266.1,P50.0%。结论 近三年来医院鲍曼不动杆菌的检出率高,对多种药物耐药率高,多重耐药严重,医院应加强对鲍曼不动杆菌感染性疾病特别是呼吸道感染的预防与控制及抗生素使用的管理,指导抗生素的合理使用,以降低医院感染率和病死率。 相似文献
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目的了解宁波市妇儿医院主要病原菌的临床分布及耐药性分析。方法血液培养采用法国生物梅里埃公司的BacT/Alert3D,菌株鉴定采用法国生物梅里埃公司的VITEK 60分析仪,药敏试验采用K-B法,纸片扩散确证试验检测ESBLs。结果前10位细菌构成比依次是大肠埃希菌(13.4%)、白色念珠菌(8.7%)、阴道加德纳菌(7.8%)、表皮葡萄球菌(6.9%)、金黄色葡萄球菌(5.6%)、肺炎克雷伯菌(4.9%)、鲍曼复合醋酸钙不动杆菌(3.9%)、粪肠球菌(D群)(3.1%)、铜绿假单胞菌(2.7%)和溶血葡萄球菌(2.0%)。大肠埃希菌539株中产ESBLs阳性率为52.5%,肺炎克雷伯菌195株中产ESBLs阳性率为45.2%。大肠埃希菌主要分离于尿液,其次是脓液/切口。肺炎克雷伯菌在痰及咽拭子中所占比例最高。46株铜绿假单胞菌和11株鲍曼复合醋酸钙不动杆菌对亚胺培南耐药。结论对产ESBLs的肺炎克雷伯菌和大肠埃希菌、耐甲氧西林金黄色葡萄球菌(MRSA)和耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)、耐亚胺培南的鲍曼复合醋酸钙不动杆菌和铜绿假单胞菌,应加强隔离预防,控制在医院内的扩散,减少耐药菌株产生。 相似文献
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对安贞医院革兰阴性杆菌的耐药趋势调查 总被引:1,自引:1,他引:1
目的分析安贞医院感染菌中,居前5位的革兰阴性杆菌的耐药趋势,为临床合理使用抗生素提供必要依据。方法对2000~2002年该院分离的医院感染菌株中,居前5位的革兰阴性杆菌的耐药性,进行回顾性分析。结果革兰阴性杆菌中前5位细菌,对3代头孢菌素的耐药性增高。大多数细菌对亚胺培南和美洛培南敏感。阿米卡星的耐药性有所下降。大肠埃希菌对喹诺酮类抗生素耐药率在85%以上。结论不规范使用抗生素,使细菌的耐药性越来越高,交替使用抗生素可能是降低细菌对抗生素耐药性的有效方法。医院应宏观控制使用抗生素。 相似文献
18.
目的了解湖州市中心医院嗜麦芽寡养单胞菌临床分布特征与耐药性。方法采用常规方法分离,用VITE-COMPACT2全自动微生物分析仪进行菌种鉴定,用K—B法进行药敏试验。结果分离到嗜麦芽寡养单胞菌810株,复方新诺明耐药菌株48株(分离率5.9%)。标本来源主要来自ICU室,其次呼吸科,大部分来自痰液标本(约占89.2%),年龄段以中老年人比率最高。嗜麦芽寡养单胞菌对亚胺培南、美罗培南、头孢吡肟、哌拉西彬他坐巴坦、庆大霉素、妥布霉素、阿米卡星高度耐药;头孢他啶、替卡西林/克拉维酸、环丙沙星耐药率为33.7%~58.2%;头孢哌酮/舒巴坦、左氧氟沙星、米诺环素、复方新诺明耐药率低于30.0%。复方新诺明耐药菌株对头孢哌酮/舒巴坦、左氧氟沙星和米诺环素耐药率分别为60.4%、91.7%和2.0%,对其余抗菌药物耐药率达100.0%。复方新诺明耐药菌株与复方新诺明敏感菌株相比,耐药情况更严重,其中对三、四代头孢菌素、喹诺酮类耐药率显著高于复方新诺明敏感菌株(P〈0.01);对碳青霉烯类、青霉素类、氨基糖苷类抗菌药物耐药率与复方新诺明敏感菌株相比,差异无统计学意义(P〉0.05)。结论嗜麦芽寡养单胞菌呈高度耐药,对头孢哌酮/舒巴坦、左氧氟沙星、米诺环素、复方新诺明尚敏感,但对复方新诺明耐药的嗜麦芽寡养单胞菌耐药现象更严重。应重视嗜麦芽寡养单胞菌引起的院内感染,尽量减少不必要的侵人性操作,加强抗菌药物的合理规范使用。 相似文献
19.
Yasuo Igarashi Yoshihiro Sanbongi Masaharu Ishii Tohru Kodama 《FEMS microbiology letters》1988,49(2):179-182
Abstract Hydrogenobacter thermophilus is an extremely thermophilic and obligately autotrophic hydrogen-oxidising bacterium with various unusual properties and believed to occupy a unique taxonomic position. Inhibitory patterns of various antibiotics on the cell growth of H. thermophilus strain TK-6 clearly showed that the bacterium possessed prokaryote-type systems of DNA, RNA and protein syntheses. Effect of ionophore antibiotics supported that the bacterium was a Gram-negative bacterium, but high sensitivities against macrolide and some other antibiotics and insensitivity against polymyxin B were unusual as a Gram-negative eubacterium.
Growth inhibition by cell wall synthesis inhibitors revealed the existence of peptidoglycan on the surface of H. thermophilus , but ineffectiveness of cell wall lytic enzymes (lysozyme and lysostaphin) on intact cells and purified cell wall strongly suggested the uniqueness of the cell wall structure of the bacterium. 相似文献
Growth inhibition by cell wall synthesis inhibitors revealed the existence of peptidoglycan on the surface of H. thermophilus , but ineffectiveness of cell wall lytic enzymes (lysozyme and lysostaphin) on intact cells and purified cell wall strongly suggested the uniqueness of the cell wall structure of the bacterium. 相似文献
20.
我国鱼类病原——嗜水气单胞的耐药性研究 总被引:20,自引:0,他引:20
采用琼脂扩散法和稀释法研究26株嗜水气单胞菌对21种菌药物的敏感性,分析了其耐药状况。结果表明:从不同地区分离收集到的26株嗜水气单胞菌(Aeromonas hydrophila)对青霉素类和头孢菌素类药物全部具耐药性,对万古霉素多数不敏感。21种药物中最敏感的是氟哌酸、氯霉素、呋喃呋酮,总体耐药率分别为7.7%、7.7%和11.5%。氨基糖甙类药物和四环素类药物的耐药频率介于其间,对磺胺药的耐药菌比例也很高,高达73.1%的A.hydrophila对磺胺及复方磺胺其有耐药性,但耐磺胺比耐复方磺胺的现象更为普遍,对3种常用药物具有耐药性的菌株比例最高。同时对鱼类病原菌耐药性的判定标准以及两种方法在鱼类病原菌耐药性研究中的适用性问题进行了讨论。 相似文献