我院2009年7月-2012年6月急诊留观病房与急诊重症监护病房病原菌及体外药敏分析

目的:探讨急诊留观病房与急诊重症监护病房(EICU)感染病原菌分布及对常用抗菌药物的药物敏感性,为指导临床治疗提供依据。方法:对2009年7月-2012年6月我院急诊留观病房与EICU送检标本细菌培养分离的菌株及临床特点进行回顾性分析,选取高检出率的大肠埃希菌、铜绿假单胞菌、鲍曼不动杆菌和金黄色葡萄球菌进行抗菌药物敏感率调查。结果:急诊留观病房分离菌株430株,EICU分离菌株296株。急诊留观病房以金黄色葡萄球菌、大肠埃希菌、铜绿假单胞菌检出最多,EICU以大肠埃希菌、鲍曼不动杆菌、铜绿假单胞菌检出最多。大肠埃希菌在急诊留观病房仅对碳青霉烯类、哌拉西林/他唑巴坦、头孢哌酮/舒巴坦敏感(敏感率>80%),而在EICU其对头孢他啶、头孢吡肟、碳青霉烯类、哌拉西林/他唑巴坦、头孢哌酮/舒巴坦、阿米卡星敏感(敏感率>80%);铜绿假单胞菌在急诊留观病房对头孢他啶、头孢吡肟、碳青霉烯类、哌拉西林/他唑巴坦、头孢哌酮/舒巴坦、阿米卡星敏感(敏感率>80%),而在EICU其仅对碳青霉烯类、头孢哌酮/舒巴坦敏感,敏感率>80%;鲍曼不动杆菌在急诊留观病房和EICU仅对碳青霉烯类、头孢哌酮/舒巴坦敏感(敏感率>80%);金黄色葡萄球菌在急诊留观病房和EICU对糖肽类抗菌药物敏感(敏感率为100%)。结论:急诊留观病房与EICU感染主要病原菌分布存在差别,主要病原菌耐药率均较高且呈多药耐药。碳青霉烯类、头孢哌酮/舒巴坦和糖肽类抗菌药物对革兰阴性菌和革兰阳性菌敏感率较高。急诊医师应参考药敏结果合理选用抗菌药物。     

2009年重庆医科大学附属第一医院细菌耐药监测

目的 调查我院2009年临床分离病原菌对抗菌药物的耐药性.方法 采用纸片扩散法进行抗菌药物敏感实验,采用WHONET5.4软件及SPSS13.0软件进行数据分析.结果 临床分类的1608株病原菌中,革兰阳性菌占25.1%,革兰阴性菌占74.9%:耐甲氧西林金黄色葡萄球菌和凝固酶阴性葡萄球菌株检出率分别为63.7%和93.7%:未发现对万古霉素或替考拉宁中介或耐药的葡萄球菌和肠球菌菌株.大肠埃希菌、肺炎克雷伯菌ESBLs检出率分别为57.2%、56.8%,肺炎克雷伯菌ESBLs的菌株高于2008年监测比例,且差别具有统计学意义(P<0.05).鲍曼不动杆菌对碳青霉烯类抗菌药物的耐药率在55%以上.结论 革兰阳性细菌对万古霉素、替考拉宁、利奈唑胺均敏感;肠杆菌对碳青霉烯类敏感性高;铜绿假单胞菌对阿米卡星敏感、头孢哌酮/舒巴坦相对敏感,鲍曼不动杆菌对碳青霉烯类耐药率高,对头孢哌酮/舒巴坦敏感性高.未发现泛耐药菌株.     

外科重症监护病房病原菌分布及耐药性分析

目的:调查外科重症监护病房(SICU)病原菌分布及耐药情况,为临床合理使用抗菌药物提供依据。方法:回顾性分析2009年1月-2012年8月武汉市儿童医院SICU临床标本中所分离出的细菌、真菌分布情况及其药敏结果。结果:共分离出病原菌400株,革兰阴性(G-)杆菌、革兰阳性(G+)球菌和真菌分别占84.25%、12.5%和3.25%;大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌、嗜麦芽窄食单胞菌和金黄色葡萄球菌位居前五位。产ESBLs酶大肠埃希菌和肺炎克雷伯菌检出率分别为54%和57.78%;耐甲氧西林金黄色葡萄球菌和凝固酶阴性葡萄球菌检出率分别为31.58%和66.67%。药敏结果显示,G-杆菌和G+球菌对临床常用抗菌药物均存在不同程度耐药性。大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌对碳青霉烯类、喹诺酮类、氨基糖苷类药物最敏感,其次为β-内酰胺抑制剂;鲍氏不动杆菌对头孢哌酮舒巴坦保持很高的敏感性(94.12%),但对碳青霉烯类耐药率达50%以上;嗜麦芽寡养单胞菌对米诺环素、复方新诺明最敏感,其次为左氧氟沙星、环丙沙星,对碳青霉烯类耐药率达100%;G+球菌对万古霉素、替考拉宁和利奈唑胺最敏感;真菌普遍敏感。结论:该院SICU优势病原菌为革兰阴性杆菌,以大肠埃希菌、肺炎克雷伯菌和铜绿假单胞菌为主。各类细菌对常用抗菌药物表现为不同程度耐药性,临床应依据细菌病原学及耐药性资料,合理选择抗菌药物。     

肠杆菌科细菌3年耐药性监测

目的了解我院2008年—2010年间临床常见肠杆菌科细菌的耐药情况及研究耐碳青霉烯类大肠埃希菌碳青霉烯酶基因型,为临床合理使用抗菌药物提供依据。方法收集我院2008-2010年间临床分离的常见肠杆菌科细菌,药敏试验使用纸片扩散法,数据分析采用WHONET5.4软件;筛选出对碳青霉烯类耐药的大肠埃希菌进行碳青霉烯酶基因的PCR检测及基因序列分析。结果 3年分离病原株共4916株,肠杆菌科共1980株,其中列前三位的是大肠埃希菌(873/1980),克雷伯菌属(605/1980)及肠杆菌属(268/1980),其次为变形菌属和沙雷菌属。主要来源于痰液、尿液及分泌物、血液、脓液等。重要肠杆菌科细菌对碳青霉烯类耐药率均小于10%,对头孢哌酮/舒巴坦、阿米卡星、哌拉西林/三唑巴坦者<30%,对广谱青霉素类及头孢菌素类者为40.9%～98.7%。变形菌属除对氨苄西林的耐药率>75%外,对其余抗生素的耐药率均低于40%,。3年来产超广谱β-内酰胺酶大肠埃希菌为33.97%及肺炎克雷伯菌57.50%,对大多数抗生素的耐药率显著高于非ELSBs菌株,且呈多重耐药。3年耐碳青霉烯类的大肠埃希菌共23株,其中产碳青霉烯酶者2株,PCR检测基因型阴性。结论本院肠杆菌科细菌大肠埃希菌和肺炎克雷伯菌检出率较高,碳青霉烯类对肠杆菌科细菌的抗菌活性最高,产ESBLs肠杆菌的耐药严重,实验室应加强对产ESBLs细菌的监测与报告。未检测出我院大肠埃希菌碳青霉烯酶基因型。治疗肠杆菌科细菌感染可选择碳青霉烯类,哌拉西林/三唑巴坦,头孢哌酮/舒巴坦,阿米卡星。     

2008年本院细菌耐药性监测

目的:了解某院临床送检标本分离株的抗菌耐药性。方法:采用K-B法,参照2008年CLSI判定标准判断结果,并用WHONET5.4软件进行数据处理。结果:1075株非重复菌株中,革兰阳性球菌246株(22.9%),革兰阴性杆菌829株(77.1%)。前5位病原菌为大肠埃希菌、铜绿假单胞菌、克雷伯菌属、不动杆菌属、凝固酶阴性葡萄球菌。MRSA、MRCNS的检出率为52.7%、79.3%。未有万古霉素不敏感菌株。产ESBLs大肠埃希菌、克雷伯菌属的检出率62.4%、28.9%,变形杆菌属对大多数抗菌药物的耐药率低于30%,肠杆菌属对大多数抗菌药物的耐药率大于40%。碳青霉烯类(亚胺培南)对肠杆菌科细菌抗菌活性较好。除头孢哌酮/舒巴坦外,不动杆菌属对其他抗菌药物的耐药率均高于铜绿假单胞菌。结论:某院临床常见病原菌革兰阴性杆菌占绝大多数,碳青霉烯类(亚胺培南)对肠杆菌科细菌抗菌活性最好,临床常见细菌对常用抗菌药物耐药性严重。     

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

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。     

我院肠杆菌科细菌对碳青霉烯类抗菌药物的耐药性分析

目的:为临床合理使用碳青霉烯类抗菌药物提供参考。方法:收集我院2014年1月-2015年12月检出的肠杆菌科细菌,采用半自动微生物测定仪进行菌株培养、鉴定及药敏试验,采用改良Hodge试验和纸片扩散法进行产肺炎克雷伯菌碳青霉烯酶(KPC)和产超广谱β-内酰胺酶(ESBLs)耐药菌株的确证。结果:我院2014-2015年共检出肠杆菌科细菌1035株,其中大肠埃希菌732株,肺炎克雷伯菌157株、阴沟肠杆菌136株、黏质沙雷菌10株,未检出枸橼酸杆菌。大肠埃希菌和肺炎克雷伯菌对阿米卡星和碳青霉烯类抗菌药物的敏感率较高,而对大部分头孢菌素类抗菌药物的敏感率较低。共检出耐碳青霉烯类肠杆菌科细菌64株(6.18%),其中耐碳青霉烯类大肠埃希菌31株(4.23%)、耐碳青霉烯类肺炎克雷伯菌30株(19.11%)、耐碳青霉烯类阴沟肠杆菌1株(0.74%)、耐碳青霉烯类黏质沙雷菌2株(20.00%);耐药菌株主要来源于痰液和尿液标本,且主要集中于新生儿内科和重症医学科。64株耐药菌株中,产KPC的有59株(92.19%)、产ESBLs的有3株(4.69%)。结论:我院肠杆菌科细菌以大肠埃希菌为主,且耐碳青霉烯类大肠埃希菌和耐碳青霉烯类肺炎克雷伯菌的检出数量较多。肠杆菌科细菌对碳青霉烯类抗菌药物的耐药性可能与其产KPC和ESBLs有关。临床应遵循用药指征,结合药敏试验结果合理选用碳青霉烯类抗菌药物。     

基层医院产ESBLs病原菌耐药性分析

目的分析致病菌中产超广谱β-内酰胺酶(ESBLs)的大肠埃希菌和肺炎克雷伯菌的耐药性,为临床合理使用抗菌药物提供依据。方法对688株致病菌检验结果进行统计学分析,了解产ESBLs病原菌的耐药情况。结果致病菌688株中革兰氏阴性菌392株占57.0%,其中大肠埃希菌和肺炎克雷伯菌共179株占45.7%,产ESBLs大肠埃希菌和肺炎克雷伯菌共84株,产酶率为46.9%(84/179),其对青霉素类和1、2、3代头孢菌素高度耐药,对亚胺培南、美罗培南高度敏感。结论大肠埃希菌和肺炎克雷伯菌是产ESBLs的主要阴性杆菌,碳青霉烯类抗生素亚胺培南、美罗培南等是治疗产ESBLs菌感染的较佳药物。     

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。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.