哌拉西林／舒巴坦对临床分离功的体外抗菌活性研究

目的比较研究哌拉西林、舒巴坦、哌拉西林与舒巴坦不同比例联合及阿莫西林/舒巴坦(21),对临床分离309株需氧菌和30株厌氧菌的体外抗菌活性及其影响因素(研究哌拉西林/舒巴坦(21)对金葡球菌、大肠埃希氏菌和铜绿假单胞菌的的杀菌曲线).方法采用琼脂平板稀释法及肉汤稀释法测定MIC值,Nitrocefin纸片法测定细菌产生的β-内酰胺酶,时间杀菌曲线采用肉汤10倍稀释法.结果对临床分离的339株需氧菌及厌氧菌体外抗菌活性研究结果显示,哌拉西林及其与舒巴坦联合时,对革兰氏阳性球菌及厌氧菌的体外抗菌活性MIC5o为1～4μg/ml,MIC90多数低于128μg/ml,优于革兰氏阴性杆菌,其MIC50为1～128μg/ml,MIC90多数高于128μg/ml;单用舒巴坦对各种细菌的体外抗菌活性极差,多数菌的MICso及MIC90分别为64及256μg/ml.对革兰氏阴性杆菌及厌氧菌,哌拉西林与舒巴坦联合时体外抗菌活性明显优于单用哌拉西林;对于革兰氏阳性球菌,哌拉西林联合舒巴坦后体外抗菌活性改善不如革兰氏阴性杆菌及厌氧菌.哌拉西林对产酶株的MIC高于非产酶株,联合舒巴坦后,产酶株MIC降低而非产酶株MIC变化不明显.不同比例联合的体外抗菌活性比较发现,以哌拉西林/舒巴坦21联合时效果较好.哌拉西林与舒巴坦21联合时,对多数临床分离菌的体外抗菌活性与阿莫西林/舒巴坦(21)的体外抗菌活性相当.本研究中,I临床分离细菌对哌拉西林的耐药率以假单胞菌属最高,达61.5%,其次是肠杆菌属细菌及大肠埃希氏菌,分别为50.8%、50.0%.哌拉西林联合舒巴坦后,所有细菌的耐药率明显下降.体外杀菌效果研究表明,当哌拉西林联合舒巴坦21时,4×MIC浓度作用于金葡球菌、大肠埃希氏菌及铜绿假单胞菌后,细菌数均随时间延长而呈指数级减少,在作用于8h细菌均被杀灭.1×MIC及2×MIC作用于以上细菌后,杀菌效果不及4×MIC.各种细菌的体外抗菌活性主要受培养基pH值及接种菌量的影响,几乎不受小牛血清白蛋白浓度的影响.结论哌拉西林/舒巴坦对β-内酰胺酶产生菌株的体外抗菌活性优于哌拉西林,以21联合效果最好,杀菌效果以4×MIC浓度最好,体外抗菌活性受培养基pH值及接种量的影响.     

注射用头孢噻肟钠他唑巴坦钠的体外抗菌活性研究

目的研究头孢噻肟钠他唑巴坦钠复方制剂对产β-内酰胺酶的头孢噻肟耐药[最小抑菌浓度(MIC)≥64μg/ml]临床分离菌的体外抗菌活性。方法采用琼脂二倍稀释法测定了不同配比头孢噻肟钠他唑巴坦钠复方制剂(CTX/TAZ1∶1、2∶1、4∶1、8∶1、16∶1)的体外MIC值,并与哌拉西林钠他唑巴坦钠(PIP/TAZ8∶1)、头孢哌酮钠舒巴坦钠(CPZ/SBT1∶1)进行比较。结果与头孢噻肟钠单独用药相比,头孢噻肟钠他唑巴坦钠复方制剂对产酶的大肠埃希菌、肺炎克雷伯杆菌、醋酸钙不动杆菌、阴沟肠杆菌、产气肠杆菌、黏质沙雷菌和异型枸橼酸杆菌的抗菌活性明显增强,MIC50至单用头孢噻肟钠的1/2～1/64。头孢噻肟钠他唑巴坦钠复方制剂对产酶的甲氧西林耐药金黄色葡萄球菌(MRSA)、甲氧西林耐药表皮葡萄球菌(MRSE)、铜绿假单胞菌的抗菌活性没有明显影响,MIC50不变或降低至1/2。他唑巴坦钠对头孢噻肟抗菌活性的增强作用随着他唑巴坦钠的加入量增加而增强,其中CTX/TAZ4∶1对大肠埃希菌(包括产超广谱β-内酰胺酶ESBLs)、肺炎克雷伯杆菌(包括产ESBLs)、醋酸钙不动杆菌、阴沟肠杆菌、产气肠杆菌、黏质沙雷菌和异型枸橼酸杆菌的MIC50分别为4、4、64、32、8、4和8μg/ml,其抗菌活性比CTX单独用药高,MIC50为单独用药的1/4～1/32。头孢噻肟/他唑巴坦4∶1对大肠埃希菌、肺炎克雷伯杆菌的抗菌活性优于哌拉西林/他唑巴坦、头孢哌酮/舒巴坦,MIC50为后两种组合的1/4～1/8。头孢噻肟/他唑巴坦4∶1对醋酸钙不动杆菌、阴沟肠杆菌、异型枸橼酸杆菌、产气肠杆菌和黏质沙雷菌的抗菌活性稍强于哌拉西林/他唑巴坦,弱于或接近于头孢哌酮/舒巴坦。结论他唑巴坦钠的加入可以有效增强头孢噻肟对除MRSA、MRSE和铜绿假单胞菌外的受试菌的敏感性。     

国产头孢三嗪的体外抗菌活性研究

本文报道国产头孢三嗪对临床分离的836株需氧菌和53株厌氧菌的抗菌活性测定,一并与其他6种头孢菌素(头孢噻肟、去乙酰头孢噻肟、进口头孢三嗪、头孢哌酮、头孢唑肟、Ceftazi-dime)和庆大霉素相比较.191株革蓝氏阳性球菌中,头孢三嗪对肺炎球菌、草绿色链球菌和溶血性链球菌的MIC_(90)≤0.06μg/ml,对金黄色葡萄球菌不产酶株及产酶株的MIC_(90)分别为4和16μg/ml,肠球菌对本品多数耐药.头孢三嗪对流感杆菌、多数肠杆菌科细菌如大肠杆菌、肺炎杆菌、拘橼酸杆菌、产气杆菌、变形杆菌、沙门氏菌、痢疾杆菌和阴沟杆菌等具有显著抗菌活性,其MIC_(90)≤0.06～0.5μg/ml,显著优于庆大霉素.头孢三嗪对绿脓杆菌虽有一定作用,但不如Ceftazidime和头孢哌酮.本品对不动杆菌属如硝酸盐阴性杆菌以及产碱杆菌等活性较差.除脆弱类杆菌外.头孢三嗪对厌氧球菌和厌氧杆菌均有一定抗菌活性.进口头孢三嗪与国产头孢三嗪的抗菌活性无显著差别.所测试的6种头孢菌素除了去乙酰头孢噻肟外,对肠杆菌科细菌均有强大活性;细菌对庆大霉素的耐药率较高,285株庆大霉素耐药菌株中,对头孢三嗪敏感者占201株(70.5%);84株头孢三嗪耐药菌中主要为绿脓杆菌(63株)和硝酸盐阴性杆菌(11株),其他菌10株.     

大蒜素联合不同药物对多重耐药鲍曼不动杆菌的体外抗菌作用

目的评价大蒜素单用及其联合亚胺培南或头孢哌酮/舒巴坦对多耐药鲍曼不动杆菌的体外抗菌作用。方法用微量肉汤稀释法,分别测定大蒜素、亚胺培南、头孢哌酮/舒巴坦对30株多耐药鲍曼不动杆菌的最低抑菌浓度(MIC);同时测定大蒜素与亚胺培南、大蒜素与头孢哌酮/舒巴坦组合药物对该菌株的MIC,计算出部分抑菌浓度指数(FICI)。结果大蒜素单药对鲍曼不动杆菌的MICrange为16～64μg.mL-1,MIC50为32μg.mL-1,MIC90为32μg.mL-1。大蒜素联合亚胺培南和大蒜素联合头孢哌酮/舒巴坦的FICI范围均为0.31～1.50。结论大蒜素单药对鲍曼不动杆菌有明显的体外抑菌作用;亚胺培南和头孢哌酮/舒巴坦均可增强大蒜的体外抗菌活性。     

哌拉西林／他唑巴坦对656株临床分离致病菌的体外抗菌作用研究

研究比较了国产哌拉西林／他佐巴坦及哌拉西林和其它联合制剂对６５６株临床分离菌的体外抗菌作用，结果表明，对大多数革兰氏阴性杆菌哌拉西林／他唑巴坦联合制剂与哌拉西林相比显示出了较强的抗菌活性，对大肠埃希氏菌、耐药粘质沙雷氏菌和铜绿假单胞菌，哌拉西林／他唑巴坦ＭＩＣ９０是哌拉西林的ＭＩＣ９０１／１６～１／３２。哌拉西林／他唑巴坦与其他酶抑制剂联合制剂抗菌活性比较表明，哌拉西林／他唑巴坦对大肠埃希氏菌、粘质沙雷氏菌、铜绿假单胞菌、变形杆菌和福氏痢疾杆菌抗菌活性比氨苄西林／舒巴坦、阿莫西林／克拉维酸和替卡西林／克拉维酸联合制剂强４～１６倍。对革兰氏阳性及革兰氏阴性球菌，哌拉西林／他唑巴坦联合制剂对肺炎链球菌、甲氧西林敏感的金葡球菌以及淋病奈瑟氏球菌的ＭＩＣ９０与哌拉西林ＭＩＣ９０相似，但对表葡球菌、其他金葡球菌和化脓性链球菌，哌拉西林／他唑巴坦联合制剂的ＭＩＣ９０是哌拉西林的１／８，而且，哌拉西林／他唑巴坦联合制剂的抗菌活性较其他酶抑制剂联合制剂强４～１６倍。对脆弱拟杆菌，哌拉西林／他唑巴坦ＭＩＣ９０是哌拉西林的１／８。     

新型碳青霉烯Biapenem对厌氧菌的体外抗菌活性

作者采用肉汤微重稀释法测定biapenem(L-627)和其它对照药对441株厌氧菌的体外抗菌作用,其结果显示 L-627对全部试验厌氧菌的MICs与亚胺培南和mero-penem相似,它们的MIC_(90)为0.06～2μg/ml.L-627对所有试验厌氧菌中的98.6%菌株的MIC≤1μg/ml,对脆弱类杆菌族MIC_(90)比氨苄西林-舒巴坦和替卡西林-克拉维酸复合剂强2～4倍、比甲硝唑和克林霉素强4～64倍,也强于亚胺培南和meropenem.L-627对大多数革兰阴性厌氧菌的活性高于甲硝唑、头孢西丁、头孢噻肟、头孢曲松和哌拉西林,与克林霉素相似.     

AZTREONAM体外抗菌活性的研究

本文报告Aztreonam对503株致病菌(包括81株多重耐药菌)的体外抗菌活性,并与其它7种抗生素进行了比较。结果显示,Aztreonam对革兰氏阳性球菌均不敏感,但对革兰氏阴性菌具有强大抗菌活性。对肠杆菌科的各种细菌(除枸橼酸杆菌外),MIC_(90) 均≤1μg/ml,抑菌率均在90％以上。本品的抗菌作用与第三代头孢菌素和Imipenem接近或略优,而明显优于Moxalactam、哌拉西林和庆大霉素。本品对枸橼酸杆菌中度敏感;对绿脓杆菌作用良好,仅次于Ceftazidine和Imipenem。在浓度为8μg/ml时,可抑制77.8％的绿脓杆菌。不动杆菌仅对Imipenem敏感。大多数菌株的MIC与MBC无显著差别。同时还测定了Aztreonam对81株多重耐药菌的抗菌作用,其中只有13株菌的MIC大于8μg/ml,总抑菌率为84.0％。本研究为Aztreonam的临床应用提供了参考。     

对革兰氏阳性菌有优良活性的新喹诺酮WIN57273的体内外活性

作者用体内外模型对新的7-二甲基吡啶取代的喹诺酮类化合物 WIN57273 进行了抗菌活性的评价。用琼脂和肉汤稀释法进行的体外实验表明它对革兰氏阳性菌和阴性菌具有广谱活性,对葡萄球菌抗菌活性最强。对凝固酶阳性葡葡球菌的 MIC_(90)≤0.002μg/ml;对凝固酶阴性葡萄球菌 MIC_(90)为0.008μg/ml;对肠球菌的 MIC_(90)为0.06μg/ml。对链球菌 A 族和 B 族以及肺炎球菌的抗菌活性与前相当。总的来说,它对革兰氏阴性菌的 MIC_(90)≤1μg/ml(除了粘质沙雷氏菌 MIC_(90)为16μg/ml,弗氏柠檬酸细菌 MIC_(90)为4μg/     

拉氧头孢对171株产超广谱β-内酰胺酶菌株的体外抗菌活性检测

采用肉汤稀释法,对100株超广谱β-内酰胺酶（ESBLS）阳性的大肠埃希菌和71株ESBLS阳性的肺炎克雷伯菌进行体外最小抑制浓度（MIC）检测,求得拉氧头孢对ESBLS阳性的大肠埃希菌与ESBLS阳性肺炎克雷伯菌的MIC50和MIC90分别是1μg/ml和8μg/ml,敏感率分别为94.0%和97.2%。实验结果表明,对产ESBLS菌株,拉氧头孢在体外保持较高的抗菌活性,临床可优先考虑选用,并可指导于临床应用。     

哌拉西林/舒巴坦对非发酵菌体外抗菌活性研究

目的 评价哌拉西林/舒巴坦对非发酵菌体外抗菌活性.方法 采用微量肉汤稀释法测定哌拉西林/舒巴坦对细菌的体外抗菌作用.结果 北京、天津、广州、哈尔滨和重庆5个城市的8家医院共收集菌株809株.对于所有铜绿假单胞菌,在8种测试药物中,哌拉西林/舒巴坦的敏感率最高(71.9%),而亚胺培南、头孢吡肟、头孢他啶、头孢哌酮/舒巴坦敏感率都低于50%.对于亚胺培南不敏感的铜绿假单胞菌,哌拉两林/舒巴坦敏感率仍可达55.8%.对于碳青霉烯敏感的鲍曼不动杆菌,哌拉西林/舒巴坦和头孢哌酮/舒巴坦敏感率最高,分别为71.0%和73.0%.对于嗜麦芽寡养单胞菌,26%和20%的菌株对哌拉西林/舒巴坦和哌拉两林/三唑巴坦的MIC≤16μg/mL.对于洋葱伯克霍尔德菌,69%的菌株对哌拉两林/舒巴坦的MIC≤16μg/mL.对于黄杆菌属和产碱杆菌属,哌拉西林/舒巴坦、头孢哌酮/舒巴坦和哌拉西林/三唑巴坦3种酶抑制剂复合制剂敏感率最高,分别为70.2%、63.2%、57.9%和94.4%、94.4%、91.7%.结论 哌拉西林/舒巴坦对于多种非发酵菌具有良好的体外抗菌活性.对碳青霉烯不敏感的铜绿假单胞菌具备一定的抗菌优势,哌拉西林/舒巴坦是经验性治疗非发酵菌感染(包括复数菌感染)的的适宜选用药物之一.     

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.