注射用法罗培南的体内抗菌活性

目的评价注射用法罗培南的体内抗菌活性。方法建立小鼠腹膜炎模型,比较注射用法罗培南及厄他培南对产酶的大肠埃希菌、肺炎克雷伯菌及对甲氧西林敏感的金黄色葡萄球菌、耐万古霉素的粪肠球菌感染小鼠的体内抗菌活性。结果注射用法罗培南对产超广谱β内酰胺酶(ESBLs)的大肠埃希菌、肺炎克雷伯菌和对甲氧西林敏感的金黄色葡萄球菌有较强的体内和体外抗菌活性,其ED_(50)分别为10.96、9.12和7.07 mg·kg~(-1),厄他培南则为14.84、12.58和10.16 mg·kg~(-1)。法罗培南对耐万古霉素的粪肠球菌体外敏感,而厄他培南显示耐药。法罗培南对耐万古霉素的粪肠球菌的ED_(50)比厄他培南低66.77%,分别为10.75和32.35 mg·kg~(-1)。结论注射用法罗培南和厄他培南对产ESBLs的大肠埃希菌、肺炎克雷伯菌和对甲氧西林敏感的金黄色葡萄球菌有较强的体内和体外抗菌活性,两者作用相似。法罗培南对耐万古霉素的粪肠球菌感染可能有治疗作用,效果优于厄他培南。     

铜绿假单胞菌感染耐药性及与β内酰胺酶的关系

目的研究本地区老年患者铜绿假单胞菌感染的分布特点及其耐药状况以及与产β-内酰胺酶的关系。方法采用K-B法测定亚胺培南等11种抗菌药物对182株铜绿假单胞菌及38株产β-内酰胺酶的铜绿单胞菌的体外抗菌活性。结果在临床分离的182株铜绿假单胞菌中,亚胺培南敏感性最高为85.71%,依次为头胞他啶(80.77%)、氨曲南(80.22%)、丁胺卡那(70.88%);在99株下呼吸道感染的铜绿假单胞菌中,亚胺培南的耐药率为24.24%,头孢他啶的耐药率为28.28%,明显高于其它部位;而在38株产β-内酰胺酶的铜绿假单胞菌中,耐药率最高的为哌拉西林(100%),其次为头孢唑啉(97.37%)和头孢噻肟(94.74%),明显高于非产酶株。结论铜绿假单胞菌感染中产β-内酰胺酶较为常见。产酶株铜绿假单胞菌的耐药性明显高于非产酶株铜绿假单胞菌的耐药性。其产生的β-内酰胺酶,是造成临床上铜绿假单胞菌对β-内酰胺类抗生素耐药的主要原因。     

细菌的耐药机制与对策

随着临床上应用的抗菌药物日益增多，耐药性问题也日益严重，目前已成为全球关注的问题，耐药菌可引起医院感染和社区感染，目前革兰阳性球菌中主要的耐药菌如甲氧西林耐药葡萄球菌（包括金葡萄MRSA和凝固酶阴性葡萄球菌MRCNS），耐青霉素肺炎球菌（PRSP）和耐万古霉素肠球菌（VRE）等，革兰阴性菌中主要的耐药菌（1）产超广谱β-内酰胺酶（ESBLs)的肠杆菌科细菌，尤其克雷伯菌属和大肠杆菌；92）产AmpC酶的阴沟、沙雷氏和枸橡酶菌。     

我院外科感染常见病原菌分布特点及耐药性检测

目的 了解外科感染常见病原菌分布特点以及对常用抗生素的耐药情况,为临床合理用药提供科学依据。方法 采用纸片扩散法(Kirby-Bauer法)对来自外科感染患者的临床分离菌进行药敏试验。按CLSI 2011版标准判断结果。结果 临床分离菌共305株,革兰阴性菌183株,革兰阳性菌122株。在各类细菌中,主要分离菌为:革兰阴性菌的大肠埃希菌、铜绿假单胞菌、肺炎克雷伯杆菌;革兰阳性菌的凝固酶阴性葡萄球菌和金黄色葡萄球菌。耐甲氧西林金黄色葡萄球菌(MRSA)和耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)检出率为23.3%和31.3%,都未发现对万古霉素耐药菌株。大肠埃希菌、肺炎克雷伯菌中产超广谱β-内酰胺酶(ESBLs)株检出率分别为34.4%和21.9%。铜绿假单胞菌对亚胺培南的耐药率为5.3%。结论 定期分析医院病原菌的耐药性,可以为临床治疗和预防感染提供依据。临床重视病原菌的检查,根据药敏试验选择合理的抗生素,可以减少细菌耐药的发生。     

2006年我院病原菌的检测情况及耐药性分析

目的:分析我院临床分离的病原菌的菌种结构及其对常用抗生素的耐药状况,为临床合理使用抗生素提供依据。方法:采用MIC法或K-B法,检测抗菌药物对常见病原菌的耐药性。结果:从住院患者中共分离出病原菌1973株,位居前7位的分别是凝固酶阴性葡萄球菌(15.97%)、大肠埃希菌(14.29%)、肺炎克雷伯菌(11.81%)、白色念珠菌(11.10%)、金葡菌(8.57%)、肠球菌(7.75%)、铜绿假单胞菌(6.79%);从门诊患者中共分离出病原菌490株,菌种构成主要为凝固酶阴性葡萄球菌(40.61%)和大肠埃希菌(30.0%);我院产超广谱β-内酰胺酶(ESBLs)的大肠埃希菌及克雷伯菌的检出率分别为48.7%和47.1%,耐甲氧西林金葡菌(MRSA)及耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)的检出率分别为67.6%和56.4%。耐药性检测结果显示:大肠埃希菌耐药率较低的抗菌药物有亚胺培南/西司他丁、美罗培南、哌拉西林/他唑巴坦等;克雷伯菌的耐药率比大肠埃希菌高;铜绿假单胞菌的耐药较为普遍,并且从第3季度开始,已出现对亚胺培南、美罗培南耐药的菌株。目前尚未发现对万古霉素耐药的MRSA及MRCNS菌株。结论:开展细菌药敏试验的检测,根据药敏试验结果合理选用抗生素,对于提高疗效,减少耐药菌株的发生具有重要意义。     

急诊科临床分离细菌耐药性分析

目的了解北京大学第一医院急诊科2012年至2015年临床分离细菌的分布及抗菌药物耐药情况。方法收集急诊科2012年至2015年临床分离的非重复细菌,用纸片扩散法或自动化仪器法进行抗菌药物敏感性试验,按照美国临床和实验室标准协会(CLSI)2015标准判定药物敏感结果,用WHONET5.6软件进行统计分析。结果临床共分离1283株细菌,其中革兰氏阳性菌占30.6%,革兰氏阴性菌占69.4%。分离最多的前5位细菌分别是大肠埃希菌(18.4%),鲍曼不动杆菌(15.2%),金黄色葡萄球菌(13.3%),铜绿假单胞菌(12.7%)和肺炎克雷伯菌(8.8%)。耐甲氧西林金黄色葡萄球菌(MRSA)的平均检出率为75.6%,耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)的平均检出率为83.1%,葡萄球菌中未发现对利奈唑胺、万古霉素耐药菌株。粪肠球菌对所测试的大多数抗菌药物的耐药率均明显低于屎肠球菌。超广谱β内酰胺酶(ESBLs)阳性大肠埃希菌的检出率为64.8%,克雷伯菌属细菌为40.5%。铜绿假单胞菌对亚胺培南、美罗培南耐药率分别为30.1%,28.4%,鲍曼不动杆菌对亚胺培南、美罗培南耐药率分别为83.5和83.0%。结论临床分离细菌对抗菌药物耐药性较高,MRSA、耐万古霉素肠球菌、泛耐药肠杆菌科细菌、泛耐药鲍曼不动杆菌、泛耐药铜绿假单胞菌的检出率较高,给临床治疗带来一定挑战。     

自贡3家三级综合医院血流感染病原菌的临床分布及耐药性分析

目的:了解自贡地区血流感染病原菌的临床分布及耐药情况,为本地区血流感染的诊断与治疗提供参考。方法:收集2017年1-12月自贡地区3家三级综合医院血培养阳性菌株及药敏结果,以大肠埃希菌ATCC25922、金黄色葡萄球菌ATCC25923、铜绿假单胞菌ATCC27853、肺炎链球菌ATCC49619为质控菌,采用WHONET 5.6及SPSS 19.0软件对血流感染病原菌的临床分布和耐药性进行分析。结果:共分离细菌879株,其中革兰氏阳性菌212株(24.1%),革兰氏阴性菌667株(75.9%);临床分布前5位的细菌分别为大肠埃希菌(50.7%)、肺炎克雷伯菌(10.2%)、金黄色葡萄球菌(6.5%)、表皮葡萄球菌(3.2%)和肺炎链球菌(2.6%)。携带病原菌患者的年龄及性别分布特点为40岁以上人群占88.5%,男女比例为1.15∶1。常见革兰氏阳性菌的耐药情况显示,未分离出耐万古霉素或利奈唑胺的金黄色葡萄球菌、凝固酶阴性葡萄球菌、粪肠球菌、屎肠球菌和肺炎链球菌,耐甲氧西林金黄色葡萄球菌(MRSA)和耐甲氧西林凝固酶阴性葡萄球菌(MRCN)的检出率分别为15.8%和64.2%;屎肠球菌较粪肠球菌对常见抗菌药物的耐药率更高,其中粪肠球菌对青霉素及氨苄西林耐药率为0,未检出耐青霉素的肺炎链球菌。常见革兰氏阴性菌的耐药情况显示,未分离出耐厄他培南的大肠埃希菌和肺炎克雷伯菌,并且这两种细菌对阿米卡星、头孢替坦、头孢吡肟、哌拉西林/他唑巴坦及亚胺培南的耐药率均较低(<10%),这两种细菌中产超广谱β-内酰胺酶(ESBLs)菌株的检出率分别为42.2%和24.4%,产ESBLs菌株比不产ESBLs菌株对常见抗菌药物耐药率更高。非发酵菌中鲍曼不动杆菌较铜绿假单胞菌对常见抗菌药物耐药率更高,两者对亚胺培南的耐药率分别为68.8%和13.6%;未分离出耐阿米卡星及妥布霉素的铜绿假单胞菌。结论:自贡地区血流感染以肠杆菌科细菌为主,鲍曼不动杆菌的耐药性严重,应加强医院感控管理。     

国内医院感染常见耐药菌的耐药特点及抗菌药应用对策

医院感染常见耐药菌，如甲氧西林耐药性金黄色葡萄球菌和甲氧西林耐药性凝固酶阴性葡萄球菌的耐药特点是对所有β-内酰胺类抗生素耐药，并常对氟喹诺酮类、氨基糖苷类、大环内酯类、克林霉素和四环素耐药，抗菌药可用万古霉素、去甲万古霉素、替考拉宁。对万古霉素耐药性肠球菌，根据药敏结果，联合用药。青霉素耐药性肺炎链球菌，治疗上可选用第三代头孢菌素类，大剂量阿莫西林+酶抑制剂。铜绿假单胞菌呈多重耐药性，对其抗菌活性较强的药物有头孢他啶、哌拉西林／三唑巴坦、亚胺培南／西司他丁、阿米卡星等。大肠埃希氏菌和肺炎克雷伯氏菌产超广谱β-内酰胺酶，抗菌药可用头霉素类、碳青霉烯类、第四代头孢菌素类、大剂量β-内酰胺类抗生素+酶抑制剂。阴沟肠杆菌产AmpC β-内酰胺，对碳青霉烯类及第四代头孢素类敏感，对非β-内酰胺类药物需根据药敏结果确定。通过对医院感染常见耐药菌的耐药特点及抗菌药应用对策进行介绍，为临床合理使用抗菌药提供参考。     

1291例血培养病原菌分布及耐药性分析

目的了解我院2011年1月至2012年12月血培养病原菌分布及耐药性,为临床感染性疾病的诊治提供依据。方法血培养采用Bact/Alert 3D全自动血培养仪,采用VITEKⅡMIC法进行病原菌鉴定及药敏试验,按照2012年美国临床实验室标准化委员会(CLSI)标准判断结果,采用WHONET5.4进行统计。结果血培养阳性率为10.11%,检出病原菌的1 291例中,革兰阳性球菌占42.91%,革兰阴性杆菌占50.97%,念珠菌属占6.12%。革兰阳性球菌主要以凝固酶阴性葡萄球菌为主,革兰阴性杆菌中以大肠埃希菌检出率最高。耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)、耐甲氧西林金黄色葡萄球菌(MRSA)检出率分别为90.8%、37.5%;粪肠球菌、屎肠球菌对庆大霉素120的耐药率分别为44.4%、72.2%,本实验未发现耐万古霉素、替考拉宁、利奈唑胺的阳性球菌。大肠埃希菌、阴沟肠杆菌均未发现耐亚胺培南菌株,肺炎克雷伯菌对厄他培南、亚胺培南的耐药率分别为3.7%、3.1%,铜绿假单胞菌对亚胺培南、美洛培南的耐药率分别为21.6%、16.2%,鲍曼不动杆菌对亚胺培南、美洛培南的耐药率分别为67.4%、50.0%,白色念珠菌未出现对抗真菌药耐药的现象。结论血流感染的常见病原菌耐药率不断增高,临床医师应及时了解血流感染病原微生物的分布及其耐药情况,为临床感染性疾病的诊治提供依据。     

天津市胸科医院2008-2009年临床分离病原菌对抗菌药耐药状况分析

目的:调查天津市胸科医院主要临床分离病原菌的种类分布及耐药趋势,为制定抗菌药物临床用药干预措施提供参考。方法:对本院2008-2009年分离菌株的种类及其药敏结果作回顾性分析。结果:主要菌种所占比例:肺炎克雷伯菌18.27%,铜绿假单胞菌13.98%,金黄色葡萄球菌12.92%,鲍曼不动杆菌10.97%。金黄色葡萄球菌和表皮葡萄球菌中耐甲氧西林金黄色葡萄球菌(MRSA)和耐甲氧西林表皮葡萄球菌(MRSE)分别为61.9%和57.8%,溶血葡萄球菌100%为甲氧西林耐药株,葡萄球菌对万古霉素100%敏感,MRSE和耐甲氧西林溶血葡萄球菌(MRSH)对莫西沙星的耐药率均<10%。大肠埃希菌、肺炎克雷伯菌中产超广谱β-内酰胺酶(ESBLs)株分别为64.6%和30%,这两种菌对碳青霉烯类药物最敏感。铜绿假单胞菌对亚胺培南和美罗培南的耐药率分别为30.6%和28.4%,对阿米卡星、哌拉西林钠/他唑巴坦钠、头孢他啶、头孢吡肟、环丙沙星、左氧氟沙星较敏感,对其他药物敏感率均<70%。鲍曼不动杆菌对亚胺培南、美罗培南、阿米卡星、哌拉西林钠/他唑巴坦钠的耐药率均<15%。结论:肠杆菌科细菌对碳青霉烯类药物最为敏感,但非发酵G-杆菌对碳青霉烯类耐药率呈上升趋势;葡萄球菌属中均未发现耐万古霉素菌株。应加强对临床病原菌的耐药监测及预警,以指导临床合理应用抗菌药物。     

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.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

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.