产ESBLs的大肠埃希菌和肺炎克雷伯菌的耐药性分析

目的探讨我院产超广谱β-内酰胺酶（ESBLs）的大肠埃希菌和肺炎克雷伯菌的耐药性变化,为临床合理使用抗菌药物提供参考依据。方法分析我院2008—2009年从临床送检的各类标本中分离得到的大肠埃希菌和肺炎克雷伯菌,采用MIC法进行药敏试验,双纸片确诊试验测定产ESBLs菌株。结果 2008年分离的764株大肠埃希菌中,产ESBLs的有312株,占40.8%;356株肺炎克雷伯菌中,产ESBLs的有133株,占37.4%。2009年分离得到的499株大肠埃希菌中,产ESBLs的有246株,占49.3%;298株肺炎克雷伯菌中,产ESBLs的有107株,占35.9%。产ESBLs菌株的耐药性显著高于非产ESBLs菌株（P〈0.05）。2009年产ESBLs的大肠埃希菌和肺炎克雷伯菌对氨曲南、头孢菌素类三代、四代药物的耐药率明显高于2008年（P〈0.05）,对喹诺酮类药物的耐药率低于2008年（P〈0.05）。2009年产ESBLs肺炎克雷伯菌对亚胺培南的耐药率较2008年上升了15.9%（P〈0.05）。结论产ESBLs的大肠埃希菌和肺炎克雷伯菌呈多重耐药现象,必须加强耐药监测,防止产ESBLs菌株的增长、扩散与流行。     

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.     

泌尿系感染病原菌产ESBLs菌株分离株的耐药性和基因型检测

目的研究鹤岗市人民医院2007年1月至2009年12月泌尿系病原茵菌株大肠埃希菌和肺炎克雷伯茵产超广谱β-内酰胺酶（ESBLs）进行确证和基因型分析,探讨ESBLs基因型的流行情况以及基因型和耐药表型的相关性。方法共收集泌尿系感染者2375例中段尿标本,采用法国生物梅里埃公司ATBExpression鉴定系统对菌株进行鉴定,采用纸片扩散法（Kirby—Bauer即K—B法）进行抗生素敏感性试验,采用双纸片协同试验筛选ESBLs菌株用CKSI推荐的确证试验进行确证,应用PCR分析,确定ESBLs基因型。结果我院ESBLs总检出率为24．2％,其中肺炎克雷伯的ESBLs检出率高达45．6％,大肠埃希菌的ESBLs检出率为21．1％。产ESBLs菌株基因型以CTX—M型为主,其次是SHV型。结论我院泌尿感染患者临床分离产ESBLs大肠埃希菌和肺炎克雷伯菌耐药情况严重,且耐药表型不同。治疗ESBLs感染首选碳青霉烯类抗菌素。     

产 ESBLs 大肠埃希菌和肺炎克雷伯菌的耐药性分析及分布

目的：了解医院临床分离的产超广谱β内酰胺酶（ESBLs）大肠埃希菌和肺炎克雷伯菌的临床分布特点及耐药状况,为临床合理用药提供参考依据。方法收集2014年医院临床分离的925株大肠埃希菌和363株肺炎克雷伯菌。使用法国生物－梅里埃 ATB 细菌鉴定系统,应用药敏测试仪及配套微生物检测试剂进行细菌鉴定和药敏试验。结果925株大肠埃希菌中分离出产 ESBLs 菌657株（占71．0％）;363株肺炎克雷伯菌中分离出产 ESBLs 菌150株（占41．32％）。产 ESBLs 大肠埃希菌来自尿标本266株（占40．49％）,产 ESBLs 肺炎克雷伯菌来自痰标本89株（占59．33％）。产 ESBLs 株的耐药率均普遍高于 ESBLs 阴性株;与产 ESBLs 肺炎克雷伯菌相比,产 ESBLs 大肠埃希菌对氟喹诺酮类抗生素耐药率较高;且二者对青霉素类、一到三代头孢菌素类抗生素耐药率均较高,而对厄它培南、亚胺培南、美罗培南等药高度敏感。结论某院产 ESBLs 大肠埃希菌主要引起泌尿道感染,产 ESBLs 肺炎克雷伯菌主要引起呼吸道感染。临床应高度重视产 ESBLs 菌的检测和药敏试验,根据药敏结果合理选择抗生素,减缓细菌耐药的发生,尤其要控制 ESBLs 菌的产生和爆发流行。     

产超广谱β-内酰胺酶大肠埃希菌和肺炎克雷伯菌耐药性及基因型研究

目的 了解宁夏地区2所医院产超广谱β-内酰胺酶(ESBLs)大肠埃希菌和肺炎克雷伯菌的耐药性及ESBLs基因型分布.方法 采用微量肉汤法测定分离自宁夏地区两家医院的45株产ESBLs的大肠埃希菌和肺炎克雷伯菌对10种抗菌药物的最低抑菌浓度(MIC),通过聚合酶链反应(PCR)法及克降测序分析其所产生ESBLs的基因型.结果 45株菌株对美罗培南全部敏感,对头孢嚷肟、奈替米星、氨苄西林、头孢噻吩、头孢曲松、复方磺胺甲噁唑、卡那霉素的耐药率均在64%以上.45株ESBLs菌株有41株产CTX-M型,其中CTX-M-14最多见,其次为CTX-M-28.结论 宁夏地区产ESBLs大肠埃希菌和肺炎克雷伯菌均存在严重的耐药性,ESBLs基因型以CTX-M-14型为主.     

产ESBLs大肠埃希菌和肺炎克雷伯菌对抗菌药的敏感性

目的：了解大肠埃希菌和肺炎克雷伯菌产超广谱β内酰胺酶（ESBLs）的发生率和耐药情况。方法：用确证试验对119株大肠埃希菌和73株肺炎克雷伯菌做ESBLs检测，K—B法做药敏试验。结果：119株大肠埃希菌检出产ESBLs54株，阳性率45．4％。73株肺炎克雷伯菌检出产ESBLs36株，阳性率49．3％。产ESBLs菌株对抗菌药的耐药率显著高于非产ESBLs菌株（P〈0．05）。结论：我院大肠埃希茵和肺炎克雷伯菌产ESBLs比例增高及对多种抗菌药呈交叉耐药和多重耐药。     

临床分离大肠埃希菌和肺炎克雷伯菌中产ESBLs菌株及其耐药基因型研究

目的 研究分离的大肠埃希菌及肺炎克雷伯菌的产ESBLs菌株的耐药情况及耐药基因的表达.方法 选取2014年1月至2015年12月我院的514例感染患者的样本作为研究对象,分离大肠埃希菌及肺炎克雷伯菌,PCR检测产ESBLs菌株的TEM、SHV、CTX-M-Ga、CTX-M-Gb及CTX-M-Gc的表达情况.结果 所有样本分离出大肠埃希菌198株,其中产ESBLs菌株101株(51.01%):TEM阳性27株(26.73%),SHV阳性32株(31.68%),CTX-M-Ga阳性17株(16.83%),CTX-M-Gb阳性13株(12.87%)及CTX-M-Gc阳性7株(6.93%).肺炎克雷伯菌114株,其中产ESBLs菌株61株(53.51%):TEM阳性11株(18.03%),SHV阳性14株(22.95%),CTX-M-Ga阳性11株(18.03%),CTX-M-Gb阳性13株(21.31%)及CTX-M-Gc阳性7株(11.48%).结论 对大肠埃希菌和肺炎克雷伯菌进行ESBLs菌株筛选及耐药基因检测,对指导临床抗菌药物的合理应用具有重要意义.     

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分析

目的了解医院临床分离产超广谱β-内酰胺酶（ESBLs）大肠埃希菌和肺炎克雷伯菌的耐药性现状,为制订临床治疗方案提供依据。方法将从临床标本分离的大肠埃希菌和肺炎克雷伯菌的药物敏感试验结果应用Whonet5.3软件进行统计学分析;产ESBLs菌株采用双纸片协同试验测定并经NCCLS确证试验确认。结果7年间产ESBLs大肠埃希菌和肺炎克雷伯菌的检出率分别为38.64%和37.33%,2005年的检出率分别为48.65%和47.73%。产ESBLs大肠埃希菌和肺炎克雷伯菌除对亚胺培南、阿米卡星、呋喃妥因敏感率高外,对所监测的其他抗菌药物耐药现象严重,且产ESBLs菌株的耐药率远高于非产ESBLs菌株。结论医院应重视对产ESBLs菌株的检测,按照药物敏感试验结果合理选用抗菌药物治疗感染;碳青霉烯类抗生素治疗产ESBLs大肠埃希菌和肺炎克雷伯菌是首选药物。     

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

目的：了解我院临床分离产超广谱β-内酰胺酶（ESBLs）大肠埃希菌和肺炎克雷伯菌的检出率及耐药性情况，为指导临床用药提供依据。方法：对我院1999—2005年分离的854株大肠埃希菌、300株克雷伯菌用标准纸片扩散确证法检测其ESBLs产生率；采用K-B法进行药敏检测。结果：1999年我院产ESBLs大肠埃希菌和肺炎克雷伯菌的检出率分别为26．4％和21．9％，2005年的两者检出率分别增长为48．6％和47．7oA。除亚胺培南的耐药率为0％、产ESBLs大肠埃希菌和肺炎克雷伯菌对阿米卡星、呋喃妥因的耐药率分别为17．9％和6．2％外，2005年我院产ESBLs菌株对其他抗菌药物耐药率均达74．4％以上，且产ESBLs菌株的耐药率远高于非产ESBLs菌株。结论：医院应重视对产ESBLs菌株的检测，合理选用抗菌药物治疗感染。对于产ESBLs大肠埃希菌和肺炎克雷伯菌感染的治疗，亚胺培南应作为首选药物。     

大肠埃希菌和肺炎克雷伯菌对头孢美唑耐药性监测

目的评价头孢美唑对大肠埃希菌和肺炎克雷伯菌体外抗菌活性及其对产β内酰胺酶（ESBLs）菌株的作用情况,为临床合理用药提供参考。方法收集住院患者各类标本中分离出的大肠埃希菌和肺炎克雷伯菌共203株,对其进行药物敏感试验及ESBLs测定。结果203株大肠埃希菌和肺炎克雷伯菌中产ESBLs株124株（占61%）,头孢美唑对大肠埃希菌和肺炎克雷伯菌产ESBLs株的耐药率高于亚胺培南、美罗培南及哌拉西林/他唑巴坦,但低于二、三、四代头孢菌素及头孢哌酮/舒巴坦。结论头孢美唑对大肠埃希菌和肺炎克雷伯菌产ESBLs株仍保持较高的抗菌活性（80%以上）,对于产ES-BLs的大肠埃希菌和肺炎克雷伯菌引起的感染仍可根据病情选用头孢美唑。     

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.     

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。     

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.     

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.     

Hyperkalaemia in patients in hospital

A survey of all laboratory blood specimens with a plasma potassium concentration greater than or equal to 5.5 mmol/L was conducted over a three month period. Of 331 specimens with hyperkalaemia, 71 were excluded because the specimens was haemolysed, old or contaminated. The laboratory served a population of 348,561 and during this time measured the plasma potassium on 25,016 occasions. Sixty-six outpatients and 20 neonates were not evaluated. The survey was undertaken on 86 of 102 inpatients (46 males), 48 of whom were over 66 years of age. Fifty-seven patients were admitted under a medical service and 29 under a surgical service. Fifty-nine had a single episode of hyperkalaemia. Thirty-two underwent a surgical procedure. The commonest contributing factor was impaired renal function which was present in 71 (83%) patients. Although a definitive causative role for drugs could be identified in only five patients, in 52 (60%) patients drugs were a contributing factor (potassium supplements 24, ACE inhibitors 16, nonsteroidal antiinflammatory drugs 12). Thirty-five of the 86 (41%) patients died during their hospital admission. Nineteen of the 35 deaths occurred within three days of the hyperkalaemia being recorded. A normal plasma potassium was eventually documented in 50 of the 86 patients. Of the remaining 36 patients, 25 (69%) subsequently died. In general the treatment of patients with hyperkalaemia focused on identifying and treating the underlying cause. Hyperkalaemia must always be considered seriously and regard given to the overall clinical status of the patient, with particular attention to drug therapy, renal and cardiac function, acid base status and the possibility of sepsis.