产超广谱β-内酰胺酶大肠埃希菌和肺炎克雷伯菌的检测与耐药性分析

目的:了解大肠埃希菌和肺炎克雷伯菌产ESBLs的检出率及耐药性。方法:采用2007年CLSI/NCCLS推荐的初筛试验方法,从352株大肠埃希菌和肺炎克雷伯菌中筛选出可疑产ESBLs细菌,并用验证试验加以确证,药敏试验采用Kirby-Bauer法。结果:大肠埃希菌和肺炎克雷伯菌ESBLs的检出率分别为42.68%(105/246)和52.83%(56/106);产ESBLs株对亚胺培南高度敏感,对头孢哌酮/舒巴坦、哌拉西林/他唑巴坦和头孢西丁耐药率较低,对其他抗菌药物的耐药率均较不产ESBLs株高。结论:重视产ESBLs细菌的检测,根椐药敏试验合理用药,亚胺培南、头孢哌酮/舒巴坦、哌拉西林/他唑巴坦和头孢西丁是目前治疗ESBLs株的有效药物。     

肝硬化并发自发性腹膜炎感染大肠埃希菌和肺炎克雷伯菌的耐药性分析

目的 探讨肝硬化并发自发性腹膜炎(SBP)感染大肠埃希菌和肺炎克雷伯菌的耐药性分析.方法 选择肝硬化并发SBP患者腹水中分离出的42株大肠埃希菌和22株肺炎克雷伯菌,采用κ-B法检测其对常用抗生素的耐药率,采用复合纸片表型确证法测定超广谱β-内酰胺酶(ESBLs).结果 从42株大肠埃希菌中检出产ESBLs菌株17株(40.5％).从22株肺炎克雷伯菌中检出产ESBLs菌株8株(36.4％).产ESBLs菌株对头孢西丁、亚胺培南、哌拉西林/唑巴坦和和头孢哌酮/舒巴坦的耐药率均低于30％.结论 肝硬化并发SBP患者腹水感染大肠埃希菌和肺炎克雷伯菌对抗生素耐药的主要原因是产生ESBLs.头孢西丁、亚胺培南、哌拉西林/他唑巴坦和头孢哌酮/舒巴坦可作为治疗的首选药物.     

老年下呼吸道感染肺炎克雷伯菌和大肠埃希菌的耐药性分析

目的探讨老年下呼吸道感染肺炎克雷伯菌和大肠埃希菌的耐药性分析及其超广谱β-内酰胺酶的检测。方法选择老年下呼吸道感染患者临床送检的标本中分离出的肺炎克雷伯菌160株、大肠埃希菌42株,采用K-B法检测其对16种常用抗生素的耐药率,采用复合纸片表型确证法测定ESBLs。结果从160株肺炎克雷伯菌中检出产ESBLs菌株58株,检出率高达36.3%。从42株肺炎克雷伯菌中检出产ESBLs菌株12株,检出率高达28.6%。产ESBLs菌对16种抗菌药物的耐药性大部分高于非产ESBLs菌。产ESBLs菌株对头孢西丁、亚胺培南、哌拉西林/他唑巴坦和和头孢哌酮/舒巴坦的耐药率均低于35%;对哌拉西林、头孢呋辛、头孢噻肟、头孢曲松、头孢他啶、头孢泊肟和环丙沙星的耐药率均高于75%。结论对老年下呼吸道感染ESBLs阳性的肺炎克雷伯菌患和大肠埃希菌患者可选择头孢西丁、头孢哌酮/舒巴坦和哌拉西林/他唑巴坦治疗,对重症感染可选择亚胺培南治疗。     

福州地区产超广谱β-内酰胺酶菌的药敏监测

目的：监测福州地区产超广谱β－内酰胺酶（ESBLs）肺炎克雷伯菌和大肠埃希菌对14种常用抗生系的药敏情况。方法：收集2001年3月－10月福州地区4家医院分离的肺炎克雷伯菌和大肠埃希菌426株，用表型确认试验检测ESBLs，用Kirby-Bauer琼脂扩散法作药敏试验。结果：426株肺炎克雷伯菌和大肠埃希菌中，共检出产ESBLs菌142株，检出率为33．33％；产ESBLs菌对大多数抗生素的耐药性严重；亚胺培南、头孢哌酮／舒巴坦、哌拉西林／三唑巴坦和头孢美唑对产ESBLs力的耐药率最低。结论：福州地区产ESBLs菌流行情况严重；产ESBLs菌对大多数抗生素耐药性严重；亚胺培南、头孢哌酮／舒巴坦、哌拉西林／三唑巴坦和头孢美唑是治疗由产ESBLs菌引起感染的有效抗生素。     

福州地区肺炎克雷伯氏菌和大肠埃希氏菌的药敏监测

目的监测福州地区肺炎克雷伯氏菌和大肠埃希氏菌对14种常用抗生素的药敏情况，为临床合理选用抗生素提供依据。方法收集2001年3月-10月福州地区4家医院分离的肺炎克雷伯氏菌和大肠埃希氏菌426株，用K-B琼脂扩散法作药敏试验；用表型确认试验检测超广谱β-内酰胺酶(ESBLs)。结果在14种抗生素中，敏感性最高的是亚胺培南(100％)、头孢哌酮／舒巴坦(100％)、哌拉西林／三唑巴坦(99．53％)、头孢吡肟(94．37％)和头孢美唑(91．08％)，敏感性最低的是阿莫西林(12．68％)、哌拉西林(48．83％)和环丙沙星(50．70％)；除头孢他啶外，第三代头孢菌素对肺炎克雷伯氏菌和大肠埃希氏菌的耐药率均在30％以上；产ESBLs菌检出率为33．33％(142／426)；除亚胺培南、头孢哌酮／舒巴坦、哌拉西林／三唑巴坦和头孢美唑外，产ESBLs菌对其它10种抗生素的耐药率均显著高于非产ESBLs菌。结论亚胺培南、头孢哌酮／舒巴坦、哌拉西林／三唑巴坦、头孢吡肟和头孢美唑的敏感性最高，产ESBLs是肺炎克雷伯氏菌和大肠埃希氏菌产生耐药的主要机制之一，临床实验室有必要常规检测肺炎克雷伯氏菌和大肠埃希氏菌是否产ESBLs。     

大肠埃希菌和肺炎克雷伯菌中AmpC酶的检测及药物敏感率分析

目的探讨大肠埃希菌和肺炎克雷伯菌AmpC酶的产生情况及对临床常用抗生素的耐药特征,为临床治疗提供选药参考。方法应用VITEK-60型全自动细菌鉴定仪鉴定细菌,按NCCLS推荐的确证试验测定ESBLs和K-B纸片法测定药敏结果;采用头孢西丁纸片扩散法筛选疑产AmpC酶阳性菌株,并用酶粗提物进行三维试验确证产AmpC酶菌株。结果 299株大肠埃希菌和肺炎克雷伯菌ESBLs检出率为19.73%,经三维试验确证产AmpC酶15株,阳性率5.02%,15株产AmpC酶阳性菌株均为ESBLs阳性菌株。产AmpC酶阳性菌株与AmpC酶阴性菌株药敏结果显示：前者大多对头孢西丁、头孢曲松、头孢噻肟、头孢哌酮、头孢他啶、哌拉西林、哌拉西林/他唑巴坦、头孢他啶/棒酸、头孢噻肟/棒酸耐药,而后者大多对上述药物敏感,两者有显著性差异（均P〈0.05）。两者大多对亚胺培南、头孢吡肟、头孢哌酮/舒巴坦、左氧氟沙星及阿米卡星敏感。结论台州地区大肠埃希菌和肺炎克雷伯菌产AmpC酶菌株检出率较高。产AmpC酶细菌呈多重耐药,亚胺培南、头孢吡肟、头孢哌酮/舒巴坦、左氧氟沙星等是治疗产AmpC酶细菌感染的较可靠药物。     

产超广谱β-内酰胺酶大肠埃希菌和肺炎克雷伯菌的耐药性研究

为了解我院产超广谱β-内酰胺酶（ESBLs）大肠埃希菌和肺炎克雷伯菌对临床常用抗菌药物的耐药情况，收集2005年1～12月住院患者标本中分离出的大肠埃希菌282株，肺炎克雷伯菌422株；以双纸片协同法检测ESBLs，KB纸片法测定11种抗菌药物的药敏性。结果表明，产ESBLs菌357株，非产ESBLs菌347株，ESBLs总检出率为50、71％（357／704）；其中产ESBLs大肠埃希菌146株，检出率为51．77％（146／282）；产ESBLs肺炎克雷伯杆菌211株，检出率为50．0％（211／422）。除产ESBLs大肠埃希菌对哌拉西林／他唑巴坦和头孢哌酮／舒巴坦耐药率与非产ESBLs菌无差异外，产ESBLs细菌对其他抗菌药物的耐药率均明显高于非产ESBLs细菌（P〈0．0236-P〈0．005之间）。所有的菌对亚胺培南100％敏感。结论：产ESBLs菌对常用抗菌药物耐药率较高，碳青霉烯类是目前治疗产ESBLs菌严重感染的最佳药物。     

产ESBLs大肠埃希菌和肺炎克雷伯菌的耐药性分析

目的了解我院2009年1～12月大肠埃希菌和肺炎克雷伯菌产超广谱β-内酰胺酶（ESBLs）菌株的分布情况及耐药性,指导临床用药。方法采用纸片扩散法（K-B法）和酶抑制剂增强纸片扩散法对396株大肠埃希菌和肺炎克雷伯菌进行检测和分析。结果大肠埃希菌和肺炎克雷伯菌ESBLs的检出率分别为52.7%和35.7%,产ESBLs菌对亚胺培南、哌拉西林/舒巴坦、头孢西丁和阿米卡星的耐药率较低。结论重视产ESBLs菌的检测,应根据药敏试验合理用药,碳青霉烯类、头孢西丁及β-内酰胺酶抑制剂复合物、阿米卡星是目前治疗产ESBLs菌比较理想的抗菌药物。     

产β-内酰胺酶菌的分离率及耐药性分析

目的：了解本地区产超广谱β-内酰胺酶（ESBLs）的主要细菌大肠埃希菌及肺炎克雷伯菌的分离率和耐药性,为临床合理选用抗菌药物提供参考。方法：采用双纸片协同法进行初筛,ESBLs确证试验进行ESBLs的检测。结果：3年中大肠埃希菌、肺炎克雷伯菌产超广谱β-内酰胺酶的检出率呈逐年上升趋势。2008～2010年大肠埃希菌产ESBLs菌株检出率分别为21.2%、30.1%、41.6%;肺炎克雷伯菌产ESBLs菌株检出率分别为19.4%、26.7%、33.0%。产ESBLs大肠埃希菌、肺炎克雷伯菌对亚胺培南、美罗培南均显示出较高的敏感性;其次是哌拉西林/他唑巴坦、头孢哌酮/舒巴坦;阿米卡星只对产ESBLs大肠埃希菌较敏感。对其他抗菌药物的耐药率在65%以上。结论：实验室应高度重视产ESBLs株的检测和细菌耐药性监测,指导临床合理选用抗生素,以及时有效控制ESBLs菌株的传播和流行。     

产超广谱β-内酰胺酶(ESBLs)菌株的检出率及耐药性分析

目的 了解本院大肠埃希菌和肺炎克雷伯菌产超广谱β-内酰胺酶(ESBLs)菌株的感染率及耐药情况,为临床合理选用抗生素提供依据,并探讨对耐药菌感染的治疗策略.方法 收集2002年8月～2006年2月从临床送检的标本中分离的大肠埃希菌和肺炎克雷伯菌共104株,采用ESBLs确证试验检测ESBLs,药敏采用NC21鉴定药敏复合板上,用AutoScan-4半自动细菌鉴定仪分析其MIC值及敏感度.结果 104株大肠埃希菌和肺炎克雷伯菌共检出产ESBLs菌17株,总检出率16.3%,产ESBLs菌呈多重耐药,对多种抗生素的耐药率明显高于非产ESBLs菌,差异有显著性.对产ESBLs菌仍保持较高活性的抗生素为亚胺培南、哌拉西林/他唑巴坦和头孢西丁,耐药率分别为0.00%,5.9%,17.6%.结论 随着抗生素的使用日益增多,基层实验室也应将ESBLs作为常规检测项目以指导临床用药,同时加大对第三代头孢菌素应用的监督,以减轻抗生素的选择压力,减少产ESBLs菌株的产生.     

Analgesics. 1. Synthesis and analgesic properties of N-sec-alkyl- and N-tert-alkylnormorphines.

A series of N-sec- and N-tert-alkylnormorphines was synthesized and evaluated for analgesic potency, antagonist activity, and opiate receptor binding. Computer-assisted conformational analysis profiles were utilized to assist in the selection of compounds for synthesis and correlation of receptor events with in vivo observations. N-tert-Alkylnormorphines 5a-c were devoid of agonist activity; however, some sec-alkyl analogues showed interesting mixed agonist-antagnoist actions. N-sec-Butyl- and N-(alpha-methylally)normorphine were separated into R and S isomers, which exhibited quantitative pharmacological differences. The N-sec-butyl S isomer 10a showed analgesia approximating morphine with nalorphine-like antagonist activity. Preliminary testing indicates only slight evidence for physical dependence with this compound.     

Discussion of S.G. Donald et al. and R. Davidson

Summary This paper discusses aspects of the papers by S.G. Donald et al. and R. Davidson, which were presented at The Econometrics Journal sponsored special session on the econometrics of inequality measurement, held at the Royal Economics Society Meeting in Surrey in 2010.     

Asthma. Role of T-lymphocytes and lymphokines.

It is now widely accepted that bronchial mucosal inflammation is an important feature of the pathogenesis of asthma. Lymphocytes probably play a role in all inflammatory responses which are antigen driven, since they are the only cells which, through the CD3/antigen receptor complex, directly recognise and respond to processed antigens. Activated T-lymphocytes, through the release of lymphokines, have the capacity to control the amount and nature of inflammatory responses. Increasing evidence is accumulating that activated CD4 T-lymphocytes participate in the inflammatory reaction observed in the asthmatic bronchial mucosa, by secreting lymphokines which attract and activate eosinophils and mast cells. CD4 T-lymphocytes may be a potentially important target for glucocorticoid therapy in asthma. Further characterisation of the functional properties of these cells might allow a definition of asthma in terms of functional abnormalities at the cellular level, and may uncover variability in asthma pathogenesis according to its aetiology.     

Pharmacokinetic differentiation of drug candidates using system analysis and physiological-based modelling. Comparison of C.E.R.A. and erythropoietin

Evaluation of the pharmacokinetics (PKs) in a proper physiological context is paramount to elucidate the factors that may improve a drug's PK properties. Using modern system analysis-based physiological modelling principles, this work applies a novel kinetic analysis framework to a PK comparison of two erythropoietically active drugs, C.E.R.A. (continuous erythropoietin receptor activator) and recombinant human erythropoietin (Epo), aimed at elucidating the main factors responsible for the substantial PK differences seen. The evaluation according to the new model is compared with a compartmental model analysis. Sheep (n = 7 for Epo; n = 8 for C.E.R.A.) received intravenous bolus injections of Epo and C.E.R.A. Baseline and 20-30 blood samples per injection were assayed by radioimmunoassay. Fundamental physiologically based PK building block principles were introduced, proceeding to the construction of a general PK model and several sub-models from which a final PK model was selected based on information theoretical principles. The compartmental comparison analysis use a two-compartment model with central Michaelis-Menten elimination. Several lines of evidence support the hypothesis that the desirable slow elimination of C.E.R.A. relative to Epo is mainly caused by a smaller recirculation extraction fraction, which appears more influential on the elimination kinetics than the mean circulation transit time. The compartmental analysis demonstrates large differences in several PK parameters that contribute to C.E.R.A.'s slower elimination, consistent with the recirculation model analysis. It is hypothesized that C.E.R.A.'s smaller recirculatory extraction fraction is due to a reduced receptor-mediated elimination, consistent with in-vitro measurements where C.E.R.A. shows Epo-receptor binding with a lower association constant and a larger dissociation constant.     

Human moricizine metabolism. II. Quantification and pharmacokinetics of plasma and urinary metabolites.

1. The metabolism of moricizine.HCl was studied in 12 male volunteers dosed with 250 mg (300 microCi) 14C-radiolabelled drug. 2. Moricizine was biotransformed to many metabolites in humans (at least 35 plasma and 51 urine metabolites). 3. Urine and faecal combined mean (range) recovery accounted for 90.2% (73.4-101.6%) of the administered radioactivity, with most of the recovered radioactivity present in faeces (mean 58.4%; range 45.6-64.7%). Mean (range) urinary recovery was 31.8% (26.2-36.9%), with <1% of the dose recovered as intact moricizine, and no one metabolite accounting for >2.5% of the dose. 4. Total radioactivity (TR) plasma t1/2 was 85.2 h, while that for moricizine was 2.4 h. Mean half-lives for plasma metabolites ranged from 2.9 to 23.6 h. The largest portion (11%) of TR AUC (area under the plasma concentration-time curve) was attributed to 2amino-10-glucuronophenothiazine. Each of the other metabolites accounted for less of the TR AUC than parent drug except for two unidentified peaks which had comparable areas (approximately 5% of the total radioactivity area). 5. Two identified moricizine metabolites, 2-amino-10-(3-morpholinopropionyl) phenothiazine and ethyl [10-(3-aminopropionyl) phenothiazin-2-yl] carbamate, possess the structural characteristics proposed for class 1 anti-arrhythmic activity (pendant amine functionality) and have plasma half-lives 4-7-fold longer than moricizine.     

Pyrrolobenzodiazepines and related systems. 2. Synthesis and biological properties of isonoraptazepine derivatives.

The synthesis of some derivatives and analogues of 12,13,14,14a-tetrahydro-9H,11H-pyrazino-[2,1-c]pyrrolo[1,2- a][1,4]benzodiazepine (isonoraptazepine) is reported. The new derivatives have been subjected to pharmacological tests for evaluation of antidepressant effects. Neurobehavioral assays were also carried out to acquire data on neurotoxicity and sedative action. Isonoraptazepine analogues and derivatives lacked the pharmacological activity of mianserin and aptazepine and showed properties similar to imipramine. Molecular modeling studies revealed structural similarities between isonoraptazepine derivatives and imipramine, thus explaining the similar pharmacological profile found in some of the tests employed. Based on pharmacological data the title compounds cannot be regarded as alpha 2 presynaptic adrenoceptors antagonists. In vitro studies for receptor binding gave support to this observation. The above studies lead us to conclude that isonoraptazepine derivatives are conformationally restricted analogues of imipramine, but their antidepressant activity cannot be correlated to inhibition of 5HT uptake. Among the derivatives tested, 7b and 8e show some affinity for the d-fenfluramine receptor site, a serotonin presynaptic site connected with anorectic activity.