碳青霉烯类抗生素的发展与展望

碳青霉烯类抗生素为一组具有特定分子结构的β-内酰胺类抗生素,对β-内酰胺酶相当稳定,杀菌活性优于头孢菌素类抗生素,是治疗产超广谱β-内酰胺酶和头孢菌素酶等多重耐药菌所致院内严重感染的首选药物。本文简述碳青霉烯类抗生素的发展史,着重介绍亚胺培南、美罗培南、比阿培南、帕尼培南、多利培南和泰吡培南酯等药物的特点及临床地位。     

碳青霉烯类耐药的肠杆菌科细菌实验室研究现状

<正>碳青霉烯类抗生素主要包括亚胺培南、美罗培南、厄他培南等,具有抗菌谱广、抗菌活性强、并具有对β-内酰胺酶稳定及毒性低等特点,已经成为临床治疗严重革兰阴性菌感染的最有效的途径。其疗效在临床上已得到广泛认可,近年随着此类药物的大量使用甚至过度治疗,碳青霉烯类耐药肠杆菌科细菌(CRE)不断增加。因其质粒携带耐药基因,CRE在细菌之间迅速传播,极易在病区内传播流行,对人体健康构成严重的威胁。本文就CRE流     

碳青霉烯类抗生素艾他培南的药理研究及其临床应用

艾他培南是新型广谱长效碳青霉烯类抗生素,抗菌活性强,对绝大多数β-内酰胺酶稳定。可用于成人复杂性腹腔感染、社会获得性肺炎、复杂性皮肤及皮肤软组织感染和尿路感染等。     

血浆万古霉素和亚胺培南的高效液相色谱测定

<正>万古霉素是糖肽类抗生素,主要用于耐甲氧西林金黄色葡萄球菌及其他细菌所致的感染。亚胺培南是碳青霉烯类抗生素,对包括需氧和厌氧的革兰阳性及革兰阴性细菌所引起的感染有效。两者都是抑制细菌细胞壁合成的药物,在细菌细胞壁合成的胞质、胞膜和胞外三个阶段中,前者抑制胞膜的多聚酶,后者抑制胞外的转肽酶~([1,2])。两药联合使用能扩大抗菌谱,增强抗菌效果,故越来越多地被临床用于不明原因的、复杂的严重感染患者。     

美罗培南的体外抗菌活性研究

目的 评价国产美罗培南对产β-内酰胺酶细菌的体外抗菌活性。方法 琼脂稀释法测定美罗培南对110株产β-内酰胺酶临床分离菌的最低抑菌浓度(MIC)。并与相关抗菌药物进行比较。结果 碳青霉烯类抗生素对产β-内酰胺酶菌株具有高度抗菌活性，国产美罗培南作用略强于亚胺培南。碳青霉烯类抗生素体外抗菌作用优于头霉素、第四代头孢菌素、β-内酰胺类抗生素与β-内酰胺酶抑制剂合剂、喹诺酮类和氨基糖苷类药物。结论 国产美罗培南是治疗产β-内酰胺酶细菌所致感染的理想药物。     

肛周脓肿感染肠杆菌科细菌分布及药敏试验结果分析

目的通过对肛周脓肿患者感染肠杆菌科细菌的分布情况及其药敏分析,为临床合理使用抗生素提供依据。方法选取大理白族自治州中医医院2016年1月至2018年12月收治的638例肛周脓肿的患者作为研究对象,分析肛周脓肿穿刺液培养检出肠杆菌科细菌的结果。结果557株肠杆菌科细菌中大肠埃希菌464株(83.3%),产超广谱β-内酰胺酶157株(33.8%);其次是肺炎克雷伯菌54株(9.69%),产超广谱β-内酰胺酶1株(1.9%);奇异变形杆菌18株(3.23%),产超广谱β-内酰胺酶1株(5.6%)。大肠埃希菌敏感率大于80.0%的抗菌药物有阿米卡星、厄他培南、美罗培南、头孢他啶、头孢西丁、头孢哌酮/舒巴坦、亚胺培南、哌拉西林/三唑巴坦。肺炎克雷伯菌敏感率大于80.00%的抗菌药物有阿米卡星、阿莫西林/克拉维酸、氨曲南、厄他培南、环丙沙星、氯霉素、美罗培南、庆大霉素、替卡西林/克拉维酸、头孢他啶、头孢西丁、头孢呋辛、头孢吡肟、头孢哌酮、头孢哌酮/舒巴坦、头孢噻肟、妥布霉素、亚胺培南、左氧氟沙星、哌拉西林/三唑巴坦。奇异变形杆菌敏感率大于80.0%的抗菌药物有阿米卡星、阿莫西林/克拉维酸、厄他培南、氯霉素、美罗培南、庆大霉素、替卡西林/克拉维酸、头孢哌酮/舒巴坦、亚胺培南、哌拉西林/三唑巴坦、氨苄西林/舒巴坦。结论治疗大肠埃希菌、肺炎克雷伯菌和奇异变形杆菌引起的肛周脓肿,经验使用抗菌药时,可选用头孢他啶、头孢西丁、阿米卡星,对于存在多重耐药菌感染高风险的患者,需考虑产超广谱β-内酰胺酶细菌感染可能,可选用头孢哌酮/舒巴坦、哌拉西林/三唑巴坦,重症感染时首选亚胺培南、美罗培南进行抗感染治疗。     

亚胺培南/西司他丁致肠道二重感染的分析与防治

亚胺培南/西司他丁是一种广谱β-内酰胺类抗生素,属碳青霉烯类与β-内酰胺酶抑制药复合制剂,抗菌谱广,抗菌作用强,尤其在目前细菌耐药性越来越严重的情况下,仍保持着很高的敏感性,显示着良好的治疗效果。但亚胺培南/西司他丁又较易引起肠道二重感染,使其应用受到了一定限制。笔者收集了国内文献对此类不良反应的报道,进行分析。     

厄他培南与头孢曲松在治疗复杂尿路感染、社区获得性肺炎、皮肤和软组织感染儿童的双盲试验中安全及耐受性比较

厄他培南已被证明是安全、耐受性好可有效治疗成人复杂尿路感染、皮肤和软组织感染以及社区获得性肺炎的碳青霉烯类抗生素。该研究对厄他培南治疗感染上述疾病的儿童进行了一项随机、双盲、活性对照的临床试验评价。     

美罗培南在国内外临床指南中的推荐

美罗培南为人工合成的广谱碳青霉烯类抗生素,该药易穿透大多数革兰阳性菌、阴性菌的细胞壁,通过抑制细菌细胞壁的合成而产生抗菌作用。除金属β-内酰胺酶以外,美罗培南对大多数β-内酰胺酶的水解作用具有较强的稳定性。由于美罗培南对多重耐药的革兰阴性杆菌均表现出较好的抗菌效果,各科指南也纷纷推荐该药用于相应感染的治疗。查阅了10余篇与美罗培南相关的抗感染治疗指南,归纳后主要有以下几类。     

儿童耐碳青霉烯类肠杆菌感染的治疗进展

<正>耐碳青霉烯类肠杆菌(CRE)是严重威胁全球公共健康的一类细菌,在全世界的发病率和病死率均呈上升趋势,它的高感染性、高死亡性和高耐药性给临床治疗带来巨大的挑战^[1-3]。CRE感染在儿童中日益普遍,往往造成不良的临床结果。近年来,随着新型β-内酰胺酶抑制剂[如头孢他啶/阿维巴坦、美罗培南/法硼巴坦、亚胺培南/西司他汀-雷利巴坦(以下简称为亚胺培南-雷巴坦)等]的出现,CRE感染的治疗模式发生了重大变化,改变了CRE感染的治疗方法。     

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.     

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.