大肠埃希菌对氨基糖苷类抗生素的耐药谱及其产ESBLs的研究

目的了解临床分离的54株大肠埃希菌对氨基糖类苷类抗生素的耐药谱及产ESBLs情况,分析氨基糖苷类修饰酶AAC(3)-II的检出率及该酶的一些特征。方法采用MIC法测定临床分离的54株大肠埃希菌对7种氨基糖苷类抗生素的耐药谱,用NCCLS推荐的酶抑制剂增强纸片扩散法检测产ESBLs菌株,并通过聚合酶链反应、克隆测序和测定重组菌耐药谱对aac(3)-II基因进行研究。结果54株大肠埃希菌对阿米卡星、庆大霉素、卡那霉素、妥布霉素、链霉素、大观霉素和奈替米星的耐药率分别为14.8%、77.8%、59.3%、66.7%、68.5%、61.1%、22.2%;共检测出产ESBLs菌株34株,占63.0%;aac(3)-II基因在54株大肠埃希菌中检出率为88.5%;质粒转化菌产ESBLs且同时检出aac(3)-II基因。重组菌BL21(DE3)/pET26::aac(3)-II对庆大霉素和卡那霉素有耐药性,对其余5种氨基糖苷类抗生素没有表现出耐药性。结论大肠埃希菌对庆大霉素的耐药率最高,对阿米卡星的耐药率最低;耐氨基糖苷类抗生素的大肠埃希菌与其产ESBLs有相关性;重组菌BL21(DE3)/pET26::aac(3)-II仅对庆大霉素和卡那霉素产生耐药。     

对氨基糖苷类的新的耐药机制

日本的研究者已鉴定出对氨基糖苷类的新的耐药机制,在铜绿假单胞菌中对所有临床有效的氨基糖苷类均显示高水平耐药。1997年从临床样品中分离出了铜绿假单胞菌AR2。研究者克隆并测定了耐药基因,把氨基糖苷耐药基因称为rmtA ,该基因可编码与16SrRNA甲基化酶非常相似的蛋白质。在他们的研究中,大肠埃希氏菌转移过度表达rmtA基因显示明显的对氨基糖苷类(包括阿米卡星、妥布霉素、异帕米星、阿贝米星、卡那霉素和庆大霉素)的耐药性,其典型的MIC为>10 2 4mg/L ,也显示阿贝卡星的耐药性可通过接合迅速地从AR2菌株转移至铜绿假单胞菌10 5 ,而…     

氨基糖苷类抗生素在儿科领域中的应用问题

氨基糖苷类抗生素（Aminoglycosides）自１９４４年链霉素发现以来，已有半个多世纪，从它们的来源可分为三类：（１）源于链霉菌属培养液，如链霉素、新霉素、卡那霉素、妥布霉素、核糖霉素；（２）源于小单包菌属培养液，如庆大霉素、西索霉素、小诺霉素等；（３）人工合成，如阿米卡星、奈替米星、依替米星等。氨基糖苷类抗生素在儿科领域中如何合理使用，必须从疗效和安全性两方面去分析。１抗菌作用特点１．１对革兰阴性杆菌作用范围大、强而持久本类药物对大多数革兰阴性杆菌如大肠杆菌、克雷白菌属、肠杆菌属，变形杆菌属、志贺菌属…     

慢性阻塞性肺疾病患者医院革兰氏阴性杆菌肺炎的分布及耐药性分析

目的 分析慢性阻塞性肺疾病(COPD)患者医院革兰氏阴性杆菌肺炎病原菌分布及耐药性。方法 回顾性分析120例COPD患者医院感染的临床资料,分析病原菌培养、药敏实验结果及诊治预后情况。结果 120例医院感染革兰氏阴性杆菌肺炎患者共计分离136株病原菌,革兰氏阳性菌4株占2.94%,革兰氏阴性菌132株占97.06%,革兰氏阴性菌中非发酵菌和肠杆菌属占比接近,非发酵菌以铜绿假单胞菌、鲍曼溶血不动杆菌为主,肠杆菌属中以大肠埃希菌、肺炎克雷伯菌为主。铜绿假单胞菌、鲍曼溶血不动杆菌对亚胺培南、头孢哌酮/舒巴坦、阿奇霉素、阿莫西林/克拉维酸的耐药率均低于10%,而对头孢唑林、头孢哌酮、头孢噻肟、哌拉西林、环丙沙星、头孢他啶耐药率则高于50%,对阿米卡星、庆大霉素、左氧氟沙星、头孢曲松的耐药率介于10%～50%之间;大肠埃希菌、肺炎克雷伯菌对亚胺培南、头孢哌酮/舒巴坦、阿奇霉素的耐药率均为0,对阿莫西林/克拉维酸耐药率低于10%,对头孢他啶、头孢唑林、头孢哌酮、环丙沙星的耐药率均高于50%,对阿米卡星、庆大霉素、左氧氟沙星、头孢曲松、哌拉西林、头孢噻肟的耐药率介于10%～50%之间。120例医院革...     

旋光法测定硫酸阿米卡星滴耳液的含量

硫酸阿米卡星的抗菌谱是氨基糖苷类中最广的，对多数细菌的抗菌作用强，且对多种氨基糖苷类钝化酶稳定，特别对耐庆大霉素、妥布霉素等的耐药菌株有很强活性。临床上主要用于对庆大霉素、妥布霉素、卡那霉素耐药菌株所致的各种严重感染。其滴眼液、滴耳液及其他溶液剂是眼科和耳鼻喉科的常用制剂，主要用于眼结膜炎、角膜炎、急慢性鼻     

甲氧苄啶与3种氨基糖苷类抗生素联用的抗生素后效应

目的:探讨甲氧苄啶 (TMP)与 3种氨基糖苷类抗生素 (庆大霉素、阿米卡星、妥布霉素 )的联合抗生素后效应 (PAE).方法:临床分离大肠埃希氏菌、肺炎克雷伯氏菌各 5株,将 8倍 MIC TMP分别与不同浓度 (1, 2, 4倍 MIC)的 3种抗生素联用,细菌与药物接触 1 h后以微量接种菌落计数法测定 PAE.结果: TMP可使 3种氨基糖苷类抗生素对 2种受试菌的 PAE显著延长,呈相加作用;联合 PAE均呈剂量依赖性.结论: TMP与氨基糖苷类抗生素联合应用可产生明显的 PAE,临床联用具有合理性.     

562株医院内获得性肺部感染的病原菌与药物敏感性结果分析

目的调查住院患者院内获得肺部感染的细菌分布和药物敏感性实验结果,为临床第一线治疗提供科学依据。方法对住院患者在院内获得肺部感染的痰液与支气管冲洗液进行细菌学培养和药物敏感性试验。结果分享培养出细菌526株,其中革兰氏阴性杆菌占80.96%(455/562),以克雷伯氏菌属的分离率最高,占52.97%(241/455),其他依次为大肠埃希菌和假单胞菌属,肠杆菌属分离最低;革兰氏阳性菌分离率占19.04%(107/562),以葡萄球菌属为主,占47.66%(51/107),其次酵母样菌属,为31.78%(34/107),链球菌属分离率最低。对10种临床常用的抗生素敏感率较高的是亚胺硫霉素,其次是氨基糖苷类,革兰氏阳性菌属对万古霉素的敏感率为89.04%,其他依次是利福平、亚胺硫霉素和庆大霉素,其中葡萄球菌属对万古霉素的敏感率为100%。结论医院内感染的病原菌以革兰氏阴性杆菌为主,对亚胺硫霉素有较高的敏感性,其次是氨基糖苷类药物。革兰氏阳性菌中则以葡萄球菌属为主,其对万古霉素敏感,其次为利福平、亚胺硫霉素和庆大霉素。     

乙基西索米星对临床分离耐药菌体外抗菌作用研究

本文研究比较了乙基西索米星及其他四种氨基糖苷类抗生素对临床分离２１９株庆大霉素耐药菌和６５株β－内酰胺类多重耐药菌的体外抗菌作用。研究结果表明，乙基西索米星对耐庆大霉素与耐β－内酰胺类的耐药金葡萄菌均有强大抗菌活性，ＭＩＣ５０与ＭＩＣ９０分别为４与８ｍ／Ｌ作用与丁胺卡那霉素相似，优于妥布霉素。乙基西索米星对耐庆大霉素与耐β－内酰胺类的肠杆菌科阴性杆菌半数以上仍有抗菌作用，其中耐β－内酰胺类的绿脓假单胞菌与不动杆菌对乙基西索来星仍高度敏感。ＭＩＣ９０分别为４与２ｍｇ／Ｌ，耐β－内酰胺类的肺炎克雷伯氏菌对乙基西索米星也不敏感。对庆大霉素高度耐药的绿脓假单胞菌对乙基西索米星、妥布霉素也耐药。对耐庆大霉素与耐β－内酰胺类多数耐药菌有效的三种氨基糖昔类抗生素中以丁胺卡那霉素作用最强，乙基西索来星次之，妥布霉素对耐药菌的作用与乙基西索米星相近，但对部分耐药菌的作用不及乙基西索米星。     

伊替米星内销“独大”，链霉素出口占优——我国氨基糖苷类抗生素产销情况分析

氨基糖苷类抗生素是上世纪50年代开始生产的一大类抗生素产品的总称。其早期代表产品为链霉素（后来国外厂商又开发出双氢链霉素等产品）。新霉素、巴龙霉素、庆大霉素、卡那霉素、阿米卡星（丁胺卡那霉素）、妥布霉素、奈替米星、大观霉素、     

常见革兰氏阴性菌耐药性动态变化特征及分析

目的 分析本地区2003年1月～2006年6月期间最常见革兰氏阴性茵(大肠埃希茵、肺炎克雷伯菌、铜绿假单胞菌和鲍曼不动杆菌)耐药性的变化,为指导临床合理使用抗菌素提供可靠依据.方法 应用回顾性调查分析方法对我院该期间临床标本分离的大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌和鲍曼不动杆菌的药敏试验进行对比统计分析.结果 近4年来,该4种细菌对常用抗菌药物的耐药率总体呈上升趋势.大肠埃希茵对头孢呋辛、头孢他啶、头孢噻肟、头孢吡肟耐药率变化显著,对大肠埃希茵保持较强抗茵活性而耐药率＜30%的抗菌药物有阿莫西林-克拉维酸、哌拉西林-三唑巴坦、亚胺培南、美诺培南、阿米卡星;肺炎克雷伯茵对哌拉西林、替卡西林-克拉维酸、头孢他啶、头孢噻肟、头孢呋辛、环丙沙星耐药率变化显著,对肺炎克雷伯菌保持较强抗菌活性而耐药率＜30%的抗菌药物有阿莫西林-克拉维酸、哌拉西林-三唑巴坦、亚胺培南、美诺培南、阿米卡星、奈替米星、妥布霉素;铜绿假单胞菌对妥布霉素、阿米卡星、庆大霉素、环丙沙星耐药率变化显著,对铜绿假单胞菌保持较强抗菌活性而耐药率＜30%的抗菌药物有替卡西林-克拉维酸、哌拉西林-三唑巴坦、头孢他啶、亚胺培南、美诺培南、阿米卡星、庆大霉素、妥布霉素、环丙沙星、多粘菌素E;对鲍曼不动杆菌保持较强抗茵活性而耐药率＜30%的抗茵药物有哌拉西林-三唑巴坦、头孢他啶、亚胺培南、美诺培南、阿米卡星.结论 本地区大肠埃希菌、肺炎克雷伯茵、铜绿假单胞菌和鲍曼不动杆菌对常用抗菌药物耐药率高,多重耐药现象严重,根据药敏结果选择抗菌药物,可有效控制和减缓细茵耐药性的增长.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.     

Trichinellosis in immigrants in Switzerland

We describe a case of trichinellosis diagnosed at the Division of Infectious Diseases, Hospital of Lugano, in January 2009. This case was associated with a cluster of cases and was traced to the consumption of contaminated meat after a wild boar hunt in Bosnia.