SCH-56592对新型隐球菌体内外抗真菌活性

目的评价新的唑类抗真菌药物SCH-56592体内外抗临床分离的新型隐球菌活性.方法依照美国国家临床试验标准化委员会推荐的M27-A方案的微量稀释法测定26株新型隐球菌对SCH-56592及氟康唑、伊曲康唑和两性霉素B的MICs.比较SCH-56592与氟康唑治疗免疫功能抑制的鼠肺隐球菌病的疗效.结果SCH-56592对于临床分离的26株新型隐球菌的体外抗菌活性是氟康唑的16～64倍,对氟康唑耐药的新型隐球菌的MIC(0.05μg@mL-1)是伊曲康唑MIC(2μg@mL-1)的1/40倍.SCH-56592不仅明显降低氟康唑敏感新型隐球菌株感染小鼠的肺内菌数(P＜0.05)[SCH-56592组为(2.90±1.90)×107CFU@mL-1,对照组为(46.60±29.58)×107CFU@mL-1];而且明显降低氟康唑耐药的新型隐球菌株感染的小鼠肺内菌数[SCH-56592组为(5.30±2.36)×107CFU-mL-1,对照组为(197.70±10.37)×107CFU@mL-1,氟康唑治疗组为(190.60±97.63)×107CFU@mL-1,与后2组比较,均为P＜0.05].肺隐球菌感染的小鼠经SCH-56592治疗后生存时间延长,生存率提高.结论SCH-56592具有良好的体内、体外抗临床分离的新型隐球菌活性;对于氟康唑耐药的新型球菌具有极好的抗真菌活性.     

248株念珠菌和新型隐球菌对四种抗真菌药的敏感性

目的　检测 2 48株念珠菌和新型隐球菌对四种抗真菌药氯康唑、两性霉素B、5 氟胞嘧啶和酮康唑的耐药状况。方法　收集临床菌株新型隐球菌 6 0株和念珠菌 188株 ,采用NCCLSM2 7 A微量稀释法测定新型隐球菌和念珠菌临床分离株对四种抗真菌药物的最低抑菌浓度 (MIC)。结果　对 16 0株白念珠菌 ,氟康唑的MIC为 0 .0 6～≥ 6 4μg/ml,敏感 135株 ( 84.38% ) ,中度敏感 10株 ( 6 .2 5 % ) ,耐药 15株 ( 9.37% ) ;5 氟胞嘧啶的MIC为 0 .0 6～ 16 μg/ml ,敏感 15 6株 ( 97.5 % ) ,中度敏感 2株 ( 1.2 5 % ) ,耐药 2株 ( 1.2 5 % ) ;两性霉素B的MIC为 0 .0 6～ 4μg/ml全部敏感 ;酮康唑的MIC为 0 .0 3～ 32 μg/ml ,敏感 93.75 % ,中度敏感 6 .2 5 %。对 6 0株新型隐球菌 ,氟康唑的MIC 1～≥ 6 4μg/ml,敏感 35株 ( 5 8.4% ) ,中度敏感 2 0株 ( 33.3% ) ,耐药 5株( 8.3% ) ;5 氟胞嘧啶MIC 0 .2 5～ 8μg/ml,敏感 5 3株 ( 88.3% ) ,中度敏感 7株 ( 11.7% ) ;两性霉素B的MIC为 0 .0 6～ 0 .5 μg/ml全部敏感 ;酮康唑MIC 0 .0 3～ 4μg/ml全部敏感。热带念珠菌和光滑念珠菌对氟康唑耐药率分别为 10 %和2 2 .2 %。结论　新型隐球菌和念珠菌对氯康唑的耐药率趋高 ,临床不容忽视。     

依维莫司单独与联合唑类药物对耐药念珠菌体外敏感研究

目的探讨依维莫司单独及联合伊曲康唑、伏立康唑、泊沙康唑和氟康唑对耐药念珠菌及耳念珠菌的体外作用。方法于 2022年 3—6月,采用美国临床实验室标准研究所 M27-A3微量稀释法和微量肉汤稀释棋盘技术研究依维莫司联合伊曲康唑、伏立康唑、泊沙康唑及氟康唑对耐药念珠菌及耳念珠菌的体外治疗作用。通过测定最低抑菌浓度( MIC)和部分抑菌浓度指数来确定协同效应。结果依维莫司单药治疗 22株耐药念珠菌及 10株耳念珠菌的 MIC为 0.250~4.000 mg/L、1.000 mg/L,伊曲康唑、伏立康唑、泊沙康唑、氟康唑单独使用对 22株耐药念珠菌 MIC范围分别为 0.125~4.000 mg/L、<0.125~2.000 mg/L、0.063~2.000 mg/L、1.000~64.000 mg/L,伊曲康唑、伏立康唑、泊沙康唑单独使用对 10株耳念珠菌 MIC范围分别为 0.500~2.000 mg/L、0.125~8.000 mg/L、0.125~1.000 mg/L。当依维莫司与伊曲康唑、伏立康唑、泊沙康唑、氟康唑联合使用时,对耐药念珠菌的协同作用分别是 9株( 40.90%)、 4株( 18.18%)、 8株( 36.36%)、 9株( 40.90%)。当依维莫司联合唑类作用于耳念珠菌,未发现任何拮抗作用。结论依维莫司单独使用对耐药念珠菌及耳念珠菌菌株具有明显抗真菌作用,同时依维莫司联合唑类作用于耐药念珠菌时,表现出良好的协同作用,且没有拮抗作用,其进一步提升其抗耐药念珠及耳念珠菌的作用。     

第九讲 抗真菌药

伏立康唑(Voriconazole)伏立康唑是一种新型的三唑类抗真菌药,于2002年在美国上市,伏立康唑的作用机制与其他三唑类药物相同。它可以口服也可静脉给药,抗菌谱较氟康唑更广,与伊曲康唑相似。【抗菌谱】本品是广谱抗真菌药,对致病性念珠菌的作用与氟康唑相当,对非白色念珠菌(如克鲁念珠菌、脱毛念珠菌)的作用稍弱;对耐氟康唑的白色念珠菌也有体外抗菌活性;对新生隐球菌的作用与伊曲康唑相似,但强于氟康唑。氟康唑对曲霉属真菌无效,而本品对广泛的曲霉属真菌具有优异的作用。较两性霉素B为强,与伊曲康唑相似;且对耐伊曲康唑和耐两性霉素B的曲…     

AIDS合并新生隐球菌感染的检测及药敏分析

目的了解临床新生隐球菌的分离及该菌对抗真菌药物的耐药情况,提高对获得性免疫缺陷综合征(AIDS)合并隐球菌感染的认识。方法对2010年5月至2012年10月我院临床分离的新生隐球菌进行统计,并分析其耐药变化。结果 23株新生隐球菌中,15株于脑脊液中分离出,占65.2%,8株分离于血液,占34.8%,脑脊液中分离出的新生隐球菌占多数,。两性霉素B、5-氟胞嘧啶、伏立康唑对新生隐球菌敏感率均为100%,氟康唑敏感率为56.5%,伊曲康唑对新生隐球菌敏感率最低为17.4%。脑脊液中分离出的新生隐球菌占多数。结论随着AIDS患者数的增多,AIDS合并隐球菌感染的发生率呈上升趋势,应加强临床合理使用抗菌药物的管理,预防和减少多药耐药菌的产生。     

苏州某三甲医院念珠菌菌血症调查及耐药性分析

摘要：目的 分析念珠菌菌血症流行病学特征及耐药情况。方法 收集2015年1月-2019年12月念珠菌菌血症中分离的65 株菌,通过显色法和质谱仪鉴定,采用微量肉汤稀释法分别测定棘白菌素、5-氟胞嘧啶、两性霉素、氟康唑、伏立康唑和伊曲 康唑MIC值并采用单中心回顾性方法收集患者的临床资料,进行Fisher精确检验和卡方检验。结果 本研究中白念珠菌和光滑 念珠菌总体分离率分别为47.7%和26.2%。伊曲康唑的总体耐药率最高为15.9%,热带念珠菌联合耐药率高为50%(P<0.001)。有 无静脉置管与念珠菌血症预后有关(P=0.018)。结论 念珠菌菌血症中白念珠菌为常见菌,光滑念珠菌在念珠菌菌血症中比例较 高。伊曲康唑对血液念珠菌耐药率高,热带念珠菌易产生唑类联合耐药。临床经验性用药应结合地区念珠菌流行病学特征。     

氟康唑与伊曲康唑治疗进行性非脑膜性球囊酵母病的对比研究

球囊酵母病是由粗球囊酵母引起的全身性感染。采用随机双盲对照试验评价氟康唑与伊曲康唑治疗进行性非脑膜性球囊酵母病的疗效。1992年 11月至 1997年 2月收治的 191名球囊酵母病患者列为研究对象 ,氟康唑治疗组患者 (n=94 )接受氟康唑 4 0 0 mg/ d;伊曲康唑治疗组患者 (n=97)接受伊曲康唑 2 0 0 mg每日 2次。各维持治疗 1年 ,分别于 8个月及 12个月时随访。8个月随访时 ,因疗效不佳终止治疗者氟康唑组2 7例 (2 8% ) ,伊曲康唑组 19例 (2 0 % ,P=0 .0 7)。氟康唑组总有效 4 7例 (5 0 % ) ,伊曲康唑组 6 1例 (6 3% ,P=0 .0 8)。 12个月随访…     

138例非HIV隐球菌性脑膜炎患者临床特征及药敏结果分析

目的 分析非HIV隐球菌性脑膜炎患者的临床特征及体外药物敏感情况。方法 回顾性分析医院2018—2021年收治的138例隐球菌性脑膜炎患者的临床资料,对患者临床表现、基础病情和实验室检查等数据进行分析。结果 138例非HIV隐球菌性脑膜炎患者墨汁染色检测阳性率为73.9%,CrAg检测阳性率为100%,42例患者存在免疫功能抑制疾病,49例伴有其他基础疾病,另外47名患者无基础疾病。患者多伴有头痛、发热、呕吐、四肢乏力和意识障碍等症状。脑脊液生化检查显示糖和氯化物减低,脑脊液蛋白升高。138株隐球菌对5-氟胞嘧啶、两性霉素B、氟康唑、伊曲康唑、伏立康唑的MIC范围分别为≤4～≥16μg/mL、≤0.5～1μg/mL、1～16μg/mL、≤0.125～0.5μg/mL、≤0.06～0.5μg/mL。5种抗真菌药物中5-氟胞嘧啶敏感性为95.60%,氟康唑敏感性为94.93%,伊曲康唑敏感性65.22%,两性霉素B和伏立康唑的敏感性均为100%。结论 隐球菌性脑膜炎患者多伴有基础疾病(含免疫功能抑制疾病);CrAg检测阳性率明显高于墨汁染色检测;非HIV隐球菌性脑膜炎患者分离菌株对不同抗真...     

天津市公安特警总队特警足部红色毛癣菌体外药敏试验

目的 本课题通过对从公安特警总队特警足部浅表真菌病分离鉴定的红色毛癣菌进行药敏试验,为公安特警中足部浅表真菌病的治疗提供依据。 [方法] 以患有足部浅表真菌病的天津市区特警总队特警为研究对象,使用M38-A2方案进行红色毛癣菌抗真菌药物敏感性研究：测定氟康唑、伊曲康唑、特比萘芬对所分离的红色毛癣菌的最低抑菌浓度(MIC)。[结果] 红色毛癣菌体外抗真菌药物敏感性研究显示氟康唑、伊曲康唑和特比萘酚对红色毛癣菌MIC值具有显著性差异。[结论] 体外抗真菌药物敏感性研究显示氟康唑、伊曲康唑和特比萘酚对红色毛癣菌MIC值具有显著性差异。     

白假丝酵母的耐药率变迁与抗真菌药物使用强度的相关性研究

目的：探究白假丝酵母的耐药率变迁与抗真菌药物使用强度(antibiotics use density,AUD)之间的相关性,为临床合理使用抗真菌药物提出参考。方法：抽取2013年—2018年医院住院病区收治的疑似真菌感染患者标本中分离出的白假丝酵母4 026株,分析其对常用抗真菌药物的耐药率及其变化趋势,并采用Pearson法分析白假丝酵母的耐药率与常用抗真菌药物使用强度的相关性。结果：2013年—2018年分离出4 026株白假丝酵母的药敏结果显示,其对氟康唑、伊曲康唑和伏立康唑的耐药率为3.42%～11.18%,呈现逐年升高趋势(P<0.05);而其对5-氟胞嘧啶的耐药率低于前3种抗真菌药物;但6年间其对两性霉素B的耐药率为0.00%;白假丝酵母对氟康唑、伊曲康唑和伏立康唑的耐药率与氟康唑的AUD呈显著正相关(r=0.908,P_0.012<0.05;r=0.939,P_0.005<0.05;r=0.838,P_0.037<0.05);对氟康唑和伊曲康唑的耐药率与卡泊芬净的AUD呈显著正相关(r=0...     

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.