产超广谱β-内酰胺酶细菌感染及耐药分析

目的分析郑州市儿童医院2008年1月至2009年12月大肠埃希菌和肺炎克雷伯菌产超广谱β-内酰胺酶(ESBLs)的耐药性变化,为临床合理使用抗菌药物提供依据。方法应用回顾性调查分析方法,对郑州市儿童医院该期间临床分离的非重复肺炎克雷伯菌和大肠埃希菌的药敏试验进行对比统计分析。结果共检出产ESBLs菌211株,检出率11.03%,其中肺炎克雷伯菌142株,检出率11.61%,大肠埃希菌69株,检出率10.00%,产ESBLs菌株对碳青霉烯类、β-内酰胺酶抑制剂复合物及喹诺酮类耐药率较低在0.00%～26.10%,而对青霉素类、头孢菌素类、单环β-内酰胺类药物则高度耐药。结论两年来产ESBLs菌的检出率与耐药率总体呈上升趋势,临床应高度重视产ESBLs细菌检测,根据药敏结果合理选择抗菌药物,碳青霉烯类、β-内酰胺酶抑制剂复合物是目前治疗ESBLs菌株感染的有效抗菌药物。     

2016至2020年上海市某三级医院肺炎克雷伯菌耐药率与抗菌药物使用强度相关性分析

目的：分析某三级综合性医院肺炎克雷伯菌耐药率与抗菌药物使用强度之间的关系,为临床合理用药提供参考依据。方法：回顾性分析2016年1月至2020年12月住院患者肺炎克雷伯菌耐药率及同期抗菌药物使用强度,使用SPSS 25.0软件进行统计分析,以Pearson进行相关性检验。结果：临床共分离肺炎克雷伯菌3017株,分离率为26.05%(3017/11580)。2016至2018年肺炎克雷伯菌对大部分抗菌药物耐药率始终保持较高水平。从2019年开始,亚胺培南和美罗培南等抗菌药物耐药率呈现下降趋势。在抗菌药物使用强度上,一代、三代头孢菌素,β-内酰胺类抗生素/β-内酰胺酶抑制剂和喹诺酮类抗菌药物使用强度呈逐年上升趋势,碳青霉烯类抗菌药物使用强度呈缓慢下降趋势。肺炎克雷伯菌对头孢唑啉的耐药率与二代头孢AUD呈正相关(P＜0.05);对哌拉西林/他唑巴坦、头孢哌酮/舒巴坦和氨苄西林/舒巴坦的耐药率与三代头孢和β-内酰胺类抗生素/β-内酰胺酶抑制剂AUD呈正相关(P＜0.05);对哌拉西林/他唑巴坦、头孢哌酮/舒巴坦和氨苄西林/舒巴坦的耐药率与碳青霉烯类AUD呈负相关(P＜0.05);头孢哌酮/舒巴坦的耐药率与喹诺酮类药物AUD呈正相关(P＜0.05)。结论：通过多个部门对抗菌药物的合理使用进行联合管控,抗菌药物耐药率在2016至2018年波动平稳,在2019年后呈下降趋势,院内管理抗菌药物合理使用初见成效,但部分抗菌药物大量使用导致耐药率仍维持较高水平,临床应继续加强抗菌药物的合理使用,做好院内管控。     

我院2014-2017年肺炎克雷伯菌耐药率与抗菌药物用药频度的相关性分析

目的分析肺炎克雷伯菌(KPN)耐药率与我院常用抗菌药物用药频度(DDDs)的相关性,促进抗菌药物合理使用。方法回顾性分析2014-2017年我院KPN检出率、产超广谱β-内酰胺酶(ESBLs)KPN的检出率、KPN对常用抗菌药物的耐药率,统计常用抗菌药物的使用频度,应用Spearman相关法分析常用抗菌药物DDDs分别与产ESBLs KPN检出率和KPN耐药率的相关性。结果产ESBLs KPN检出率与酶抑制剂合剂类药物累计DDDs呈显著正相关(r=0.641,P<0.01);KPN对美罗培南的耐药率与碳青霉烯类累计DDDs、美罗培南DDDs、第2代头孢菌素累计DDDs和头孢呋辛DDDs均呈正相关(r=0.531、0.514、0.773、0.634,P<0.05),与第1代头孢菌素累计DDDs呈负相关(r=-0.762,P<0.05);对左氧氟沙星的耐药率与喹诺酮类累计DDDs和左氧氟沙星DDDs均呈正相关(r=0.683、0.497,P<0.05);对头孢哌酮舒巴坦的耐药率与酶抑制剂合剂累计DDDs呈负相关(r=-0.580,P<0.05);对头孢他啶的耐药率与头孢曲松DDDs呈负相关(r=-0.500,P<0.05)。结论某些抗菌药物DDDs与KPN对抗菌药物耐药率以及产ESBLs菌株检出率具有相关性。     

重症监护室患者耐碳青霉烯类肺炎克雷伯菌感染危险因素分析

目的：了解重症监护室（ICU）中导致肺炎克雷伯菌感染患者耐碳青霉烯类抗菌药物的危险因素,为减少耐药菌的产生提供依据,以减少医院感染的发生。方法：收集某院2017-2018年ICU内经细菌培养鉴定为肺炎克雷伯菌的菌株,按药敏试验结果分为耐碳青霉烯肺炎克雷伯菌组（CRKP组,43例）和非耐碳青霉烯肺炎克雷伯菌组（KP组,109例）。统计每例患者基本情况、感染部位、住院时间、手术、首次检出阳性前抗菌药物使用情况等,分析其与耐碳青霉烯类肺炎克雷伯菌产生的相关性。结果：2组中均是痰标本中分离的占首位,其次是血液、尿液以及创面分泌物等。CRKP感染危险因素的单因素分析可见,患者高龄（P=0.032）,合并慢性肾功能不全（P=0.019）、恶性肿瘤（P=0.024）,患者机械通气时间、ApacheⅡ评分、感染部位个数是感染CRKP的危险因素（P<0.05）。首次检出CRKP/KP前,患者接受碳青霉烯类或者喹诺酮类药物治疗（P<0.001）是CRKP感染的危险因素。非线性Logstic回归分析显示,患者年龄、住院时间、合并恶性肿瘤、感染部位个数、机械通气时间、ApacheⅡ评分,接受碳青霉烯类、喹诺酮类治疗为CRKP感染的独立危险因素（P<0.05）。结论：应进一步规范碳青霉烯类及喹诺酮类药物的使用,同时针对危险因素高的患者做好有效医院感染预防控制措施,以减少耐碳青霉烯类肺炎克雷伯菌医院感染的发生,延缓耐碳青霉烯类肺炎克雷伯菌的传播。     

肠杆菌属所致院内呼吸道感染的耐药现状及治疗策略

目的:为临床诊治肠杆菌属所致院内呼吸道感染提供参考。方法:通过查阅近年来国内外相关文献,对肺炎克雷伯菌和大肠埃希菌所致的院内呼吸道感染的耐药现状,对临床的影响及治疗策略进行归纳和总结。结果:我国肺炎克雷伯菌和大肠埃希菌耐药形势严峻,治疗产超广谱β-内酰胺酶(ESBLs)肠杆菌所致院内呼吸道感染可首选β-内酰胺酶抑制剂复合制剂(如,哌拉西林/他唑巴坦)、替加环素或碳青霉烯类;治疗产碳青霉烯酶肠杆菌所致院内呼吸道感染可应用多黏菌素、替加环素、磷霉素。结论:β-内酰胺酶抑制剂复合制剂治疗产ESBLs肠杆菌的临床疗效好,不良反应少,可作为肠杆菌属所致院内呼吸道感染的合理选择。     

我院2013～2015年住院患者抗菌药物应用分析

目的分析并评价我院住院患者抗菌药物的应用情况,为合理使用抗菌药物提供参考依据。方法利用信息系统收集2013~2015年我院抗菌药物的使用数据,对抗菌药物的费用比例、用药频度(DDDs)及日均费用(DDC)等进行回顾性分析。结果我院住院患者使用抗菌药物DDDs排名前10位的药品基本来自头孢菌素类、其他β-内酰胺类、喹诺酮类、硝基咪唑类及青霉素类复方制剂,住院患者抗菌药物占总销售金额的比例逐年上升,头孢菌素类使用频度较高,部分药物DDC较高。结论我院还存在部分药物DDDs偏高的情况,应严格限制头孢菌素类(尤其是三代头孢菌素)、其他β-内酰胺类、喹诺酮类(尤其是左氧氟沙星)及青霉素类复方制剂的临床应用,避免DDDs的过快增长,加强监督和管理。     

我院2008-2010年抗菌药物应用与细菌耐药性分析

目的:了解我院抗菌药物应用及细菌耐药情况。方法:调取我院2008-2010年抗菌药物的出库数据,采用限定日剂量法分析抗菌药物应用情况;利用我院检验科2009-2010年细菌耐药监测数据,分析临床分离菌对抗菌药物耐药率。结果:头孢菌素尤其是第3代头孢菌素类应用最为频繁;同期临床分离菌以大肠埃希菌、肺炎克雷伯菌与葡萄球菌为主;葡萄球菌对青霉素几乎完全耐药,耐甲氧西林葡萄球菌检出比率较高,尚未见对万古霉素耐药的金黄色葡萄球菌;大肠埃希菌与肺炎克雷伯菌对第3代头孢菌素已显示出较高的耐药率,但对碳青霉烯类、含β-内酰胺酶抑制剂复方制剂(除氨苄西林/舒巴坦)、头霉素类与阿米卡星等均仍敏感。结论:第3代头孢菌素有滥用倾向;临床分离菌以大肠埃希菌、肺炎克雷伯菌与葡萄球菌为主,细菌耐药情况比较严重,须引起重视。     

2012-2017年某院耐碳青霉烯肺炎克雷伯菌变迁及耐药性

目的 分析医院耐碳青霉烯肺炎克雷伯菌(CRKP)的流行趋势、分布特点及耐药性,为CRKP的防治提供临床依据。方法 调查某院2012-2017年住院患者抗菌药物使用情况及CRKP分离率和耐药数据,采用χ2检验、Spearman相关性检验等进行分析。结果 6年共分离肺炎克雷伯菌1911株,其中280株为CRKP。CRKP检出率由2012年的0.4%上升至2017年的29.5%;重症监护病房(ICU)CRKP的分离率明显高于普通病房(P<0.05);CRKP检出与碳青霉烯类、第三代头孢菌素和青霉素酶抑制剂复方制剂的使用强度呈明显的正相关(P<0.05)。CRKP株对大多数抗菌药物的耐药率超过90%。结论 该院CRKP分离率较高,与入住ICU及广谱β-内酰胺类、碳青霉烯类的用量有关,呈现多重耐药性。应加强抗菌药物管理,强化消毒、隔离等医院感染控制措施,以减少耐药株的播散和流行。     

产超广谱β-内酰胺酶的大肠埃希菌和肺炎克雷伯菌的临床分布及耐药性分析

<正>大肠埃希菌和肺炎克雷伯菌是医院获得性感染的重要病原菌~([1])。近年来,随着第三、四代头孢菌素类和单环β-内酰胺类抗菌药物在临床上的的广泛应用,诱导细菌耐药株的不断增加,许多细菌产生了多重耐药性。医学超广谱β-内酰胺酶(ESBLs)是由质粒介导的能水解所有青霉素类、头孢菌素类和单环β-内酰胺类氨曲南但能被克拉维酸抑制的一类酶,主要由大肠埃希菌、肺炎克雷伯菌及鲍曼不动杆菌等产     

2011年重庆涪陵中心医院住院患者抗菌药物应用分析

目的：了解2011年我院住院患者抗菌药物使用情况,给临床合理用药提供参考。方法：提取2011年每月我院住院患者抗菌药物消耗数据,对用药频度（DDDs）、限定日费用（DDC）、抗菌药物使用强度（AUD）等进行统计分析。结果：2011年我院住院患者抗菌药物使用剂型以注射剂为主;头孢菌素类和β-内酰胺＋β-内酰胺酶抑制剂复方制剂占抗菌药物总DDDs的1/2,头孢菌素类中又以第3代头孢菌素的DDDs最高;大环内酯类的使用主要以口服制剂为主。氟喹诺酮类与β-内酰胺＋β-内酰胺酶抑制剂复方制剂的DDDs、AUD和销售金额构成比逐月下降。结论：我院抗菌药物使用日趋合理,但仍存在用药不合理现象,有待进一步提高。     

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.     

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.     

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.