糖尿病足复发感染病原菌的分布及耐药性分析

目的对糖尿病足复发感染病原菌的分布及耐药性进行分析。方法选取杭州师范大学附属医院2014年6月至2015年6月收治的且符合纳入标准的糖尿病足复发感染患者120例。对所有患者糖尿病足复发感染病原菌的分布及耐药性进行分析。结果 120例糖尿病足复发感染患者共检出病原菌145株,其中18例为混合细菌感染。145株细菌中革兰阳性菌91株(62.8%),前三位的分别为金黄色葡萄球菌、粪肠球菌、链球菌,分别占28.3%、24.8%、6.2%;革兰阴性菌41株(28.3%),以大肠埃希菌、绿脓假单胞菌属、奇异变形杆菌为主,分别占6.9%、6.2%、5.5%。不同病原菌对常用抗菌药物呈现不同程度的耐药;革兰阳性球菌对青霉素、红霉素耐药严重,而对头孢曲松、万古霉素较为敏感,对万古霉素未出现耐药情况。革兰阴性菌对亚胺培南、美罗培南均敏感,其次对阿米卡星较敏感,对氨苄西林耐药率最高。结论糖尿病足患者复发感染病原菌分布广泛,应根据药物敏感性试验结果及时调整抗菌药物,以利于促进创面早期愈合。     

泌尿外科住院患者泌尿系感染病原菌分布及其耐药性分析

了解泌尿外科住院患者泌尿系感染病原菌的分布及其对常用抗菌药物的耐药情况。对泌尿外科泌尿系感染住院患者的消毒中段尿培养结果进行回顾性分析,尿培养菌株的鉴定、药敏分析和统计分析采用VITEK2全自动微生物仪。3 a中泌尿外科泌尿系感染住院患者共分离到细菌1 233株,其中革兰阴性杆菌772株,占62.61%,革兰阳性球菌353株,占28.63%,真菌82株,占6.65%。菌株数居前5位的细菌依次为:大肠埃希菌、肠球菌属、洋葱伯克霍尔德菌、假丝酵母菌属和变形杆菌。分离大肠埃希菌产ESBLs率为66.18%,粪肠球菌中未发现VRE菌株,屎肠球菌VRE为0.8%。未发现对美洛培南耐药的大肠埃希菌,对肠埃希菌耐药率在10%以下的有亚胺培南、阿米卡星、哌拉西林/他唑巴坦和呋喃妥因。洋葱伯克霍尔德菌和铜绿假单胞菌对所监测的抗菌药物均有不同程度的耐药。未发现对万古霉素、替考拉宁及氨苄西林耐药的粪肠球菌。泌尿系感染的病原菌以大肠埃希菌和肠球菌为主,非发酵革兰阴性杆菌及假丝酵母菌所占比例超过20%,不容忽视,病原菌的耐药率较高,临床医生应根据尿培养和药敏试验结果合理使用抗菌药物。     

糖尿病患者足部溃疡感染的病原菌分布及药敏性分析

目的:研究糖尿病患者足部溃疡感染的病原菌分布及药敏性。方法:选取2016年2月至2017年2月我院收治的糖尿病足患者102例作为研究对象,采用全自动细菌鉴定仪和Kirby-Baure(K-B)法分别检测所有患者足部溃疡分泌物中病原菌分布和药敏性。结果:96例成功分离出菌株的糖尿病患者足部溃疡分泌物中共分离出107株菌株,其中革兰阴性菌61株(57.01%)、革兰阳性菌43株(40.19%)和真菌3株(2.80%),占总菌株百分比前三位的病原菌分别为金黄色葡萄球菌22株(20.56%)、奇异变形杆菌14株(13.08%)和肺炎克雷伯菌10株(9.35%);前三位革兰阴性菌(奇异变形杆菌、肺炎克雷伯菌和大肠埃希菌)对亚胺培南、美罗培南、头孢哌酮及阿米卡星的敏感性较高(高于90.00%);金黄色葡萄球菌和表皮葡萄球菌对万古霉素、利奈唑胺及利福平敏感性较高(高于95.00%);粪肠球菌对红霉素、氨苄西林、万古霉素及利奈唑胺敏感性较高(高于90.00%)。结论:糖尿病患者足部溃疡感染的病原菌以金黄色葡萄球菌和奇异变形杆菌为主,耐药情况严峻,临床诊疗过程中应根据药敏结果规范使用抗菌药物。     

糖尿病足感染的细菌学调查及耐药性分析

目的 了解临床糖尿病足患者感染的细菌分布及耐药性分析.方法 2009年至2010年,共调查135例糖尿病足患者.结果 检出细菌株数为107株,其中革兰阳性菌44株,占41.1％;革兰阴性菌57株,占53.3％;真菌6株,占5.6％.需氧菌感染80例,检出率59.3％.以金葡菌、链球菌、变形杆菌和大肠埃希菌为主要感染菌.金黄色葡萄球菌的耐药率明显低于其他葡萄球菌.大肠埃希菌治疗以亚胺培南首选,也可选用β-内酰胺类加酶抑制剂.结论 检出革兰阴性菌57株,革兰阳性菌44株,应根据药敏情况合理应用抗菌素.     

外科血培养标本中病原菌分布及耐药性分析

目的了解中山大学附属第一医院外科血标本中病原菌的菌种分布及常见菌株的耐药性。方法血标本用Bact/A lert-120全自动血培养仪进行血培养,阳性血培养转种后用VITEK-60 AMS细菌鉴定仪鉴定,用K-B法进行药敏试验。结果2002年1月至2005年12月血培养标本中共分离出病原菌256株,阳性率为10.6%。122株(47.7%)为革兰阴性杆菌,其中肠杆菌科细菌占72.1%(88/122),非发酵菌占27.9%(34/122);113株(44.1%)为革兰阳性球菌,其中葡萄球菌属占51.3%(58/113),肠球菌占38.1%(43/113);真菌21株(8.2%)。血培养中的革兰阴性杆菌对亚胺培南、美洛培南治疗敏感;革兰阳性球菌对万古霉素和替考拉宁敏感。结论肠杆菌科细菌和葡萄球菌是外科血培养中的主要病原菌,其耐药现象严重,宜根据药敏结果选用敏感抗菌药物治疗。     

女性泌尿道感染常见细菌菌群分布及耐药性分析

目的了解中山大学第一附属医院近5年住院及门诊女性尿路感染致病菌菌群分布及耐药性情况,为临床合理使用抗生素提供依据。方法选择2002年1月至2006年4月门诊及住院女性尿培养阳性的尿路感染患者,分析其细菌培养结果及对抗生素的耐药性。结果共分离出876株病原细菌,革兰阴性菌占76.7%(672株),其中大肠埃希菌占49.2%(431株),肺炎克雷伯菌占7.9%(70株);革兰阳性菌占23.3%(204株),其中粪肠球菌占7.5%(66株),屎肠球菌占5.4%(47株)。主要的革兰阴性菌及革兰阳性菌对喹诺酮类的耐药性均高达50%~80%以上,革兰阴性菌敏感的抗菌药包括亚胺培南、阿米卡星、头孢他啶、哌拉西林/他唑巴坦;革兰阳性菌敏感的抗菌药包括万古霉素、替考拉宁。结论女性泌尿道感染仍以大肠埃希菌为主,耐药菌株不断增多,临床治疗应参考药敏结果合理选用抗菌药。     

239株脑脊液标本非重复分离株病原学分布与药物敏感试验结果分析

目的通过回顾性分析脑脊液培养结果的病原菌分布与药物敏感试验结果,分析中枢神经系统感染相关细菌的耐药性及其变化趋势。方法选取西安交通大学医学院第一附属医院2012年1月至2014年9月期间从临床患者脑脊液标本中分离培养出的细菌,所有菌株均采用全自动微生物分析仪进行鉴定,仪器法与纸片法检测其对抗生素的敏感性。用WHONET 5.6软件进行数据统计分析。结果本研究共包含非重复分离菌株239株,其中革兰阳性菌175株(74%),革兰阴性菌59株(24%),真菌5株(2%)。革兰阳性菌主要为葡萄球菌属、肠球菌属与链球菌属细菌,其中表皮葡萄球菌最为常见。革兰阴性菌主要为肠杆菌科细菌与非发酵革兰阴性杆菌,其中鲍曼不动杆菌、肺炎克雷伯杆菌、大肠埃希菌最为常见。真菌均为新型隐球菌。分离菌株中革兰阳性菌与革兰阴性菌均有不同程度的耐药现象,革兰阳性菌仅对利奈唑胺、替考拉宁、万古霉素敏感率为100%,革兰阴性菌中肠杆菌仅对阿米卡星、美洛培南、哌拉西林/他唑巴坦、亚胺培南敏感率为90%以上,而鲍曼不动杆菌对各类抗生素耐药率均在80%以上。结论中枢神经系统感染以革兰阳性菌为主,表皮葡萄球菌为最常见的分离菌株。多重耐药菌的出现,使中枢神经系统感染的治疗面临巨大挑战,提示临床合理使用抗生素进行抗感染治疗至关重要。     

主要医院感染病原菌与社区感染株耐药性比较

目的比较主要医院感染(HAI)病原菌与社区感染(CAI)株的耐药性,指导合理使用抗菌药物。方法收集永康市第一人民医院2003年1月至2006年6月所有标本中分离的主要HAI菌及其CAI株,分别统计其药物敏感试验。采用美国Dade Behring Microscan Walkaway 40全自动细菌鉴定及药敏测试仪及其配套药敏鉴定板测定MIC值。全国医院感染监测网软件和χ2统计分析。结果主要HAI菌为前4种革兰阳性(G )菌依次是金黄色葡萄球菌、表皮葡萄球菌、屎肠球菌、溶血葡萄球菌,前5种革兰阴性(G-)菌依次是大肠埃希菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌、阴沟肠杆菌。HAI株耐药率普遍高于CAI株,不同的细菌耐药率各具特点。不论HAI株还是CAI株,G 菌对万古霉素的耐药率最低,G-菌对亚胺培南的耐药率均较低,且两者耐药率差异均无显著性。金黄色葡萄球菌、大肠埃希菌、肺炎克雷伯菌、鲍曼不动杆菌4种HAI株对大多数抗菌药物的耐药率明显高于CAI株,其余5种细菌HAI株仅对少数抗菌药物的耐药率高于CAI株。结论HAI菌株耐药性比CAI菌株强,临床应区分感染性质合理使用抗菌药物,有针对性控制感染,从而减少抗菌药物的滥用和细菌耐药性的产生。     

细菌菌群的分布及耐药性分析

目的：了解本院临床分离致病菌菌群的分布及耐药情况,给临床经验用药提供可靠依据。方法：按《全国临床微生物检验操作规程》培养分离菌种,用美国BD公司的Sceptor半自动细菌鉴定仪或法国梅里埃公司的Vitek-60细菌鉴定仪进行鉴定及药物敏感实验,结果：临床分离 的致病菌中革兰阳性球菌占39．6％,革兰阴性杆菌占60．4％,前5位细菌分别为铜绿假单胞菌188株（17．0％）,大肠埃希菌143株（13．0％）,表皮葡萄球菌140株（12．7％）,肠球菌115株（10．7％）,金黄色葡萄球菌109株（9．9％）,药敏结果显示,苯唑西林耐药葡萄球菌（MRS）的耐药率明显高于苯唑西林敏感葡萄球菌109株（9．9％）,药敏结果显示,苯唑西林耐药葡萄球菌（MRS）的耐药率明显高于苯唑西林敏感葡萄球菌（MSS）,球菌中未分离出万古霉素耐药的菌株,但肠球菌中检测出有对万古霉素中介的菌株;肠杆菌科细菌对亚胺培南的耐药率最低,铜绿假单胞菌对头孢他啶,头孢哌酮,氨曲南,丁胺卡那霉素,亚胺培南的耐药率亦较低。结论：革兰阴性杆菌分离率高于革兰阳性球菌;革兰阳性球菌对万古霉素敏感率最高,肠杆菌科对亚胺培南敏感率最高,非发酵菌对亚胺培南,氨基糖甙类,头孢他啶,头孢哌酮药蓄亦较低。     

舟山地区2688例胆汁培养病原菌分布及耐药性分析

目的通过分析2007年到2010年舟山医院2 688例胆汁标本中病原菌的分布及耐药状况,为临床合理用药提供实验依据。方法对2 688例胆汁标本进行细菌培养、鉴定和药敏分析。结果 2 688例胆汁标本中共检出阳性标本611例(阳性率22.7%),其中革兰阴性菌占82.2%(502/611),革兰阳性菌占13.3%(81/611),真菌占4.6%(28/611)。主要的病原菌为大肠埃希菌(40.3%)、肺炎克雷伯菌(15.4%)、肠球菌(11.3%);阴沟肠杆菌(4.7%)等。大肠埃希菌和肺炎克雷伯菌的ESBLs阳性菌株的比例达到了21.0%和5.9%,其中ESBLs阴性菌株对头孢他啶、头孢吡肟、美罗培南和阿米卡星等药物较为敏感,而ESBLs阳性菌株只对美罗培南和亚胺培南敏感;革兰阳性菌对万古霉素、氨苄西林较敏感。结论舟山地区胆道感染以革兰阴性菌为主,大肠埃希菌产ESBLs的菌株有较高的比例,临床应加强对抗生素的合理使用。     

量子点在新药开发中的应用

由于具有优异的光学特性,量子点在生物医学领域内的研究和应用取得了一些有意义的进展,同时也引起了新药开发人员的兴趣.本文概述了量子点在新药开发中所具有的优势,分析了量子点在药物传输、药物筛选和药靶确证方面的潜在应用,进一步讨论了当前量子点应用于新药开发存在的问题和不足.     

现代生物学对药物发现的影响

随着后基因组时代的到来,药物发现研究领域不断涌现出一系列新思路、新技术、新方法,从而迅速推进药物发现的多元化发展。一方面,基因组学、蛋白质组学、转录组学、代谢组学、生物信息学、系统生物学等新兴学科的崛起与发展,为药物发现提供更为广泛而深刻的理论基础;另一方面,计算机辅助药物设计、高通量筛选、高内涵筛选、生物芯片、转基因和RNA干扰等高新技术的发展和完善,为药物发现提供了新的技术手段和有力工具,极大地拓宽了药物发现的途径。本文结合近年来现代生物学的研究进展,综述现代生物学对药物发现过程的影响。     

Recent Advances in Drug Repositioning for the Discovery of New Anticancer Drugs

Drug repositioning (also referred to as drug repurposing), the process of finding new uses of existing drugs, has been gaining popularity in recent years. The availability of several established clinical drug libraries and rapid advances in disease biology, genomics and bioinformatics has accelerated the pace of both activity-based and in silico drug repositioning. Drug repositioning has attracted particular attention from the communities engaged in anticancer drug discovery due to the combination of great demand for new anticancer drugs and the availability of a wide variety of cell- and target-based screening assays. With the successful clinical introduction of a number of non-cancer drugs for cancer treatment, drug repositioning now became a powerful alternative strategy to discover and develop novel anticancer drug candidates from the existing drug space. In this review, recent successful examples of drug repositioning for anticancer drug discovery from non-cancer drugs will be discussed.     

从创新药物申报角度探讨中美新药评审制度的异同

创新药物研发是国家医药产业发展的原动力,美国作为全球新药研发能力最强的国家,这与其食品药品管理局在新药审批过程中给 予的技术支持和政策鼓励密不可分。通过分析比较我国与美国的新药评审相关政策的异同,学习和借鉴美国的成功经验,为我国创新药物 注册审评制度的调整与完善提供参考。     

壳聚糖作为药物缓释控释载体的研究进展

壳聚糖因其具有良好的生物学特性而成为多种药物载体研究的热点。药物经过壳聚糖负载后,不仅能够达到缓释控释的目的,还能够改变药物的给药方式,以此减少给药次数,降低药物不良反应,提高药物生物利用度。本文就壳聚糖和改性壳聚糖作为普通药物和生物大分子药物载体的研究进展作一综述。     

人Toll样受体靶向药物研究进展

Toll样受体(TLR)是一类模式识别受体,通过多种信号传递改善免疫系统功能,活化NF-κB信号通路,调节TNF-α、ILs和IFN-α等多种细胞因子分泌,在天然免疫系统中发挥重要作用,在免疫学及药物研究领域受到广泛关注。TLR种类众多,配体广泛,可以作为治疗微生物感染、炎症、自身免疫性疾病、 肿瘤及放射损伤等疾病的药物靶点,是免疫治疗的重要切入点。研究人员已经对数十种TLR靶向药物进行了研究。对TLR结构特征、信号传递以及靶向药物的特点和研究现状进行综述,分析其在免疫治疗方面的优劣势,也为下一步药物研究提供一定的理论依据。     

Applications of primary human hepatocytes in the evaluation of pharmacokinetic drug-drug interactions: Evaluation of model drugs terfenadine and rifampin

The utility of primary human hepatocytes in the evaluation of drug-drug interactions is being investigated in our laboratories. Our initial approach was to investigate whether drug-drug interactions observed in humans in vivo could be reproduced in vitro using human hepatocytes. Two model drugs were studied: terfenadine and rifampin, representing compounds subjected to drug-drug interactions via inhibitory and induction mechanisms, respectively. Terfenadine was found to be metabolized by human hepatocytes to C-oxidation and N-dealkylation products as observed in humans in vivo. Metabolism by human hepatocytes was found to be inhibited by drugs which are known to be inhibitory in vivo, Ki values for the various inhibitors were derived from the in vitro metabolism data, resulting in the following ranking of inhibitory potency: For the inhibition of C-oxidation, ketoconazole > itraconazole > cyclosporin ~ troleandomycin > erythromycin > naringenin. For the inhibition of N-dealkylation, itraconazole ketoconazole > cyclosporin naringenin erythromycin troleandomycin. Rifampin induction of CYP3A, a known effect of rifampin in vivo, was also reproduced in primary human hepatocytes. Induction of CYP3A4, measured as testosterone 6-hydroxylation, was found to be dose-dependent, treatment duration-dependent, and reversible. The induction effect of rifampin was observed in hepatocytes isolated from all 7 human donors studied, with ages ranging from 1.7 to 78 years. To demonstrate that the rifampin-induction of testosterone 6-hydroxylation could be generalized to other CYP3A4 substrates, we evaluated the metabolism of another known substrate of CYP3A4, lidocaine. Dose-dependent induction of lidocaine metabolism by rifampin is observed. Our results suggest that primary human hepatocytes may be a useful experimental system for preclinical evaluation of drug-drug interaction potential during drug development, and as a tool to evaluate the mechanism of clinically observed drug-drug interactions.     

Mutagenesis of the putative nucleotide-binding domains of the multidrug resistance associated protein (MRP). Analysis of the effect of these mutations on MRP mediated drug resistance and transport

Studies were conducted to examine the functional role of the nucleotide-binding domains of MRP in drug resistance and drug transport in isolated membrane vesicles. In vivo studies were conducted by preparing stable transfectants of HeLa cells with wild-type MRP cDNA or MRP cDNAs which had been mutated at certain nucleotide binding domains (NBD). Stable transfectants producing equivalent amounts of the MRP encoded protein P190 were used in this study. The results demonstrated that deletions in the C-motif of NBD1 or the A-motif of NBD2 have a pronounced effect in reducing resistance levels to chemotherapeutic agents. Certain single-site mutations in lysines in these same motifs also reduce IC₅₀ values. It has also been observed that mutation of the MRP NBDs results in an increase in drug accumulation and a reduction in drug efflux. Additional studies have been carried out in which recombinant baculovirus containing either wild-type MRP or MRP containing mutated NBDs was prepared and used to infect SF21 insect cells. Using this system we have analyzed the effects of these mutations on in vitro transport of leukotriene C₄ (LTC₄) 17 β-estradiol 17 (β-D-glucuronide)(E₂17βG) and daunomycin in membrane vesicles prepared from baculovirus infected cells. The results demonstrate that deletions and site-specific mutations in MRP NBDs greatly reduce the ATP dependent transport of all three substrates. The results of these studies conducted both in vivo and in vitro demonstrate that the NBDs of MRP function in a cooperative manner and are critical for the transport activity of the MRP encoded protein P190. These studies also identify specific lysines in NBD1 and NBD2 which are important for optimal MRP activity. This revised version was published online in August 2006 with corrections to the Cover Date.     

Comparison of the Ames assay and the induction of sister chromatid exchanges: Results with ten pharmaceuticals and five selected agents

Seven antischistosomal drugs, two antimalarial drugs, and one antiamoebic drug were tested in all five Ames strains for induction of mutation, as well as for induction of cytotoxicity, inhibition of cellular progression, and the induction of sister chromatid exchanges in two cultured mammalian cell lines. We found that two agents shown to be negative in the Ames test were positive for sister chromatid exchange induction. Based on qualitative and quantitative evaluation, we find that all but three of the pharmaceuticals should be considered to be potential human carcinogens.Abbreviations AA 2-aminoanthracene - 9AACC 9-aminoacridine - AM amoscanate - BrdUU bromodeoxyuridine - CA chloroquine diphosphate - CHO Chinese hamster ovary - CQ chloroquine - DAPI 46-diamidino-2-phenylindole - DHY dehydroemetine - DMSO dimethyl sulfoxide - EB ethidium bromide - FCS fetal calf serum - FN 4-fluoro-3-nitrophenyl azide - HY hycanthone - ICP inhibiting cell progression - LU lucanthone - MEM minimal essential medium - 2NF 2-nitrofurantoin - 4NPD 4-nitro-O-phenylenediamine - NZ niridazole - OL oltipraz - OX oxaminiquine - PBS phosphate buffered saline - PQ primaquine - PZ praziquantel - SA sodium azide - SCE sister chromatid exchange     

Pharmacogenetics of cardiovascular drugs.

Pharmacogenetics is a field aimed at understanding the genetic contribution to inter-patient variability in drug efficacy and toxicity. Treatment of cardiovascular disease is, in most cases, guided by evidence from well-controlled clinical trials. Given the solid scientific basis for the treatment of most cardiovascular diseases, it is common for patients with a given disease to be treated in essentially the same manner. Thus, the clinical trials have been very informative about treating large groups of patients with a given disease, but are slightly less informative about the treatment of individual patients. Pharmacogenetics and pharmacogenomics have the potential of taking the information derived from large clinical trials and further refining it to select the drugs with the greatest likelihood for benefit, and least likelihood for harm, in individual patients, based on their genetic make-up. In this paper, the current literature on cardiovascular pharmacogenetics is emphasised, and how the use of pharmacogenetic/pharmacogenomic information may be particularly useful in the future in the treatment of cardiovascular diseases is also highlighted.