2016—2020年医院碳青霉烯类抗菌药物与常见碳青霉烯耐药革兰阴性杆菌调查分析

目的 调查分析2016—2020年医院碳青霉烯类抗菌药物与常见碳青霉烯耐药革兰阴性杆菌(CRGNB)检出情况,为规范碳青霉烯类抗菌药物临床应用管理和耐药菌防控提供参考。方法 对2016—2020年重庆医科大学附属永川医院碳青霉烯类抗菌药物使用与碳青霉烯耐药肺炎克雷伯菌(CRKP)、碳青霉烯耐药大肠埃希菌(CREC)、碳青霉烯耐药鲍曼不动杆菌(CRAB)、碳青霉烯耐药铜绿假单胞菌(CRPA)的检出情况进行回顾性分析,并采用Spearman相关系数考察相关性。结果 2016—2019年碳青霉烯类抗菌药物消耗量、使用强度均呈增加趋势,2020年有所下降; 2016—2020年4种常见碳青霉烯耐药革兰阴性杆菌检出中CRAB最高、CRPA次之、CREC最低;CRPA、CREC的检出与部分碳青霉烯类抗菌药物使用呈负相关性(r=-0.900,P <0.05)。结论 医院碳青霉烯类抗菌药物使用呈上升趋势,CRGNB中鲍曼不动杆菌对碳青霉烯类抗菌药物耐药性较严重;目前仍需重视碳青霉烯类抗菌药物的临床应用管理,继续加强细菌耐药监测。     

多黏菌素类联合其他抗菌药物治疗耐碳青霉烯类革兰阴性菌感染的研究进展

随着耐碳青霉烯类革兰阴性菌检出率不断增加,多黏菌素类抗菌药物成为治疗耐碳青霉烯类革兰阴性菌感染的一种重要选择。但单一多黏菌素类抗菌药物治疗存在局限性,如常规剂量效果不佳,而增加剂量又会导致不良反应和耐药风险增加等。目前以多黏菌素类抗菌药物为基础的多药联合方案广泛应用于耐碳青霉烯类革兰阴性菌感染的治疗,但最佳联合治疗方案,以及不同联合治疗方案的安全性、有效性等尚无一致的定论。本文对基于多黏菌素类抗菌药物的联合用药方案在治疗耐碳青霉烯鲍曼不动杆菌、肺炎克雷伯菌和绿假单胞菌等革兰阴性菌感染的体内、体外研究进展进行综述,以期为多黏菌素类抗菌药物用于耐碳青霉烯类革兰阴性菌所致感染的治疗提供相关依据。     

74株呼吸科革兰阴性杆菌感染的临床原因及其耐药性分析

目的:分析呼吸内科住院患者革兰阴性杆菌感染的临床原因及其耐药性,为临床诊治和合理用药提供参考。方法:选取2015年3月—2016年8月间医院呼吸内科收治的革兰阴性杆菌感染患者52例,从中分离出74株革兰阴性菌,采用药敏试验检测其对抗菌药物的耐药性。结果:从52例呼吸内科住院患者的标本中,分离出革兰阴性杆菌74株(鲍曼不动杆菌14株、阴沟肠杆菌6株、肺炎克雷伯菌20株、大肠埃希杆菌11株、铜绿假单胞菌11株和其他菌株12株);铜绿假单胞菌、鲍曼不动杆菌、肺炎克雷伯菌和阴沟肠杆菌对抗菌药物的耐药率较高。结论:分离出革兰阴性杆菌中,菌株中以肺炎克雷伯菌、鲍曼不动杆菌所占百分率为最高;而铜绿假单胞菌、鲍曼不动杆菌、肺炎克雷伯菌和阴沟肠杆菌对抗菌药物的敏感率为最低。     

2017—2018年天津市宝坻区人民医院血流感染病原菌分布及耐药性分析

目的 探讨天津市宝坻区人民医院血流感染病原菌的分布及耐药性情况,为临床合理用药提供依据。方法 对2017-2018年天津市宝坻区人民医院血流感染病原菌的分布及耐药性进行回顾性分析。结果 共分离出病原菌365株,主要分布在普通内科、呼吸内科和儿科。其中革兰阴性菌228株,构成比为62.47%,主要为大肠埃希菌、肺炎克雷伯菌和鲍曼不动杆菌;革兰阳性菌137株,构成比为35.34%,主要为凝固酶阴性葡萄球菌和金黄色葡萄球菌;真菌8株,构成比为2.19%。大肠埃希菌、肺炎克雷伯菌对头孢菌素类、喹诺酮类和氨基糖苷类等抗菌药物存在不同程度的耐药性,但对酶抑制剂（头孢哌酮/舒巴坦、哌拉西林/他唑巴坦）较为敏感,对碳青霉烯类抗菌药物保持较高敏感性;鲍曼不动杆菌对第3代头孢菌素（头孢曲松、头孢噻肟）的耐药率达到了90%以上,对碳青霉烯类抗菌药物耐药率未超过20%。凝固酶阴性葡萄球菌和金黄色葡萄球菌对万古霉素、利奈唑胺无耐药性。目标性治疗应用抗菌药物中,革兰阴性菌所致血流感染多选择美罗培南（21.20%）、头孢哌酮/舒巴（14.96%）和哌拉西林/他唑巴坦（10.72%）;革兰阳性菌所致血流感染多选择万古霉素（19.45%）。结论 天津市宝坻区人民医院血流感染病原菌主要以革兰阴性菌为主,应加强血流感染病原菌的耐药性监测,以指导抗菌药物的合理使用。     

潜在DCD供者携带耐碳青霉烯革兰阴性菌的危险因素分析

目的 探讨潜在公民逝世后器官捐献(DCD)供者携带耐碳青霉烯革兰阴性菌(CRGNB)的危险因素。方法 器官获取组织评估的潜在DCD供者319例。收集供者的人口学特征、临床基本数据、既往慢性病史、侵入性操作等一般资料,采用单因素分析及多因素logistic回归分析潜在DCD供者携带CRGNB的危险因素。结果 潜在DCD供者CRGNB分离率为22.6%(72/319);共分离出CRGNB 98株(前3位是鲍曼不动杆菌、绿脓杆菌和肺炎克雷伯菌)。分离标本主要来源于痰液、血液和尿液。多因素logistic回归分析示,ICU停留>5 d、有呼吸道感染、有糖尿病病史和碳青霉烯类抗生素应用史是潜在DCD供者携带CRGNB的独立危险因素(P<0.05)。结论潜在DCD供者携带CRGNB危险因素为ICU停留>5 d、有呼吸道感染、糖尿病病史和碳青霉烯类抗生素应用史。针对此类供者应加强CRGNB筛查,并积极建立早期预警机制。     

2014-2019年某医院血流感染患者的临床特征和病原学分析

摘要：目的 分析血流感染(bloodstream infection, BSI)患者的临床特征和病原菌情况,为BSI治疗和院内感染防控提供依据。方法 回顾性分析2014年8月-2019年7月上海交通大学医学院附属瑞金医院北部院区BSI住院患者的临床和病原学资料,采用Whonet 5.6软件进行耐药统计。结果 196例患者发生BSI,男132例,平均年龄62岁;90.8%患者有基础疾病,59.2%有侵袭性操作史,41.8%有局部感染灶,所有患者均发热,主要来自重症监护室、普外科和血液科。共分离病原菌208株,其中革兰阴性菌113株(54.3%)、革兰阳性菌73株(35.1%)、真菌21株(10.1%),分离率最高的为肺炎克雷伯菌,其次为凝固酶阴葡萄球菌(CNS)、大肠埃希菌、鲍曼不动杆菌、金黄色葡萄球菌、粪肠球菌和屎肠球菌等。CNS和金黄色葡萄球菌对甲氧西林耐药率分别为89.7%和37.5%,分离的所有革兰阳性菌对万古霉素、利奈唑胺和替加环素100%敏感;大肠埃细菌和肺炎克雷伯菌产超广谱β-内酰胺酶(ESBLs)检出率分别为56.7%和58.1%,大肠埃细菌对碳青霉烯类无耐药;肺炎克雷伯菌对替加环素耐药率较低(7.1%),对亚胺培南和美罗培南耐药率分别为34.1%和45.2%;鲍曼不动杆菌对临床常用抗菌药物耐药率较高,对亚胺培南和美罗培南耐药率分别为57.1%和66.7%。结论 患者的年龄、基础疾病、侵袭性操作史和局部感染灶等因素可能与血流感染发生有关,本研究血流感染病原菌以革兰阴性菌为主,肺炎克雷伯菌和鲍曼不动杆菌对包括碳青霉烯类在内的多种常用抗菌药物耐药率较高。     

某院74例呼吸衰竭合并肺部感染患者的病原菌分布及主要病原菌的耐药性分析

目的:分析呼吸衰竭伴发肺部感染患者的病原菌分布及主要病原菌的耐药特点.方法:选取医院2019年12月-2020年12月老年病科收治的呼吸衰竭伴发肺部感染患者74例病历资料,统计其患者痰标本的病原菌培养和药敏结果,分析其病原菌的分布特点及其革兰阴性菌的耐药特点.结果:74例肺部感染患者标本中,检出病原菌82株,呼吸机相关性肺炎(Ventilator associated pneumonia,VAP)患者标本中检出57株、非VAP患者标本中检出25株;其中,革兰阴性菌69株(占84.15％,以铜绿假单胞菌、鲍曼不动杆菌、肺炎克雷伯菌为主),革兰阳性菌13株(占15.85％);药敏结果发现主要革兰阴性菌中铜绿假单胞菌、鲍曼不动杆菌、肺炎克雷伯菌对庆大霉素、头孢曲松、头孢哌酮、复方磺胺甲嗯唑、亚胺培南等常用抗菌药物的耐药率较高,其中鲍曼不动杆菌对米诺环素以外抗菌药物均具有高度耐药.结论:呼吸衰竭患者伴发肺部感染常见病原菌为铜绿假单胞菌、鲍曼不动杆菌、肺炎克雷伯菌,且其对常用抗菌药物具有较高的耐药率,临床应根据病原菌分布特点与药敏结果选用敏感率高的抗菌药物治疗.     

2011-2013年我院碳青霉烯类抗菌药物耐药情况分析

目的 分析该院2011-2013年碳青霉烯类抗菌药物耐药情况,为今后医院临床合理用药提供参考.方法 用纸片扩散法进行抗菌药物敏感试验,参照CLSI2012标准,用WHONET5.5软件进行数据分析.结果 革兰阴性菌中肠杆菌科细菌大肠埃希氏菌、肺炎克雷伯菌、产气肠杆菌、产酸克雷伯菌等对碳青霉烯类敏感率为100％;非发酵菌鲍曼不动杆菌、铜绿假单胞菌对碳青霉烯类抗菌药物耐药率在不断升高.结论 非发酵菌对碳青霉烯类抗菌药物耐药性在不断升高,应严格管理碳青霉烯类抗菌药物的临床应用.     

2016—2019年安徽省某三级医院呼吸科与ICU卒中相关性肺炎病原菌分布及耐药性

目的 分析呼吸科与重症监护病房(ICU)卒中相关性肺炎(SAP)病原菌分布变迁、耐药性特点,为临床合理使用抗菌药物提供参考。方法 回顾性分析2016年1月至2019年6月呼吸科及ICU收治SAP患者病原菌及药敏结果,调查产超广谱β-内酰胺酶(ESBLs)及耐碳青霉烯类抗生素病原菌(CRO)比率。结果 呼吸科共检出病原菌41株,其中革兰阴性杆菌38株(92.69%),革兰阳性球菌3株(7.32%),依次为肺炎克雷伯菌16株(39.02%),铜绿假单胞菌7株(17.07%),鲍曼不动杆菌6株(14.63%)等。ICU共检出病原菌137株,革兰阴性杆菌128株(93.43%),革兰阳性球菌9株(6.57%),依次为肺炎克雷伯菌43株(31.39%),鲍曼不动杆菌38株(27.74%),铜绿假单胞菌16株(11.68%)等。呼吸科产ESBLs肺炎克雷伯菌、耐碳青霉烯肺炎克雷伯菌(CRKP)所占比率分别为50%和12.5%,而ICU分别为41.86%和2.33%;呼吸科耐碳青霉烯鲍曼不动杆菌(CRAB)、耐碳青霉烯铜绿假单胞菌(CRPA)所占比率分别为66.67%和28.57%,而ICU依次为97.37%和37.5%。ICU中鲍曼不动杆菌对于碳青霉烯类抗生素耐药性显著高于呼吸科 (P＜0.05)。结论     

ICU抗菌药物用量与革兰阴性菌耐药的相关性分析

目的 分析我院2013—2018年ICU抗菌药物用量与常见革兰阴性菌耐药率变化的关系,为临床合理使用抗菌药物提供参考。方法 回顾性调查我院ICU病房6年来抗菌药物用量和常见革兰阴性菌的分布情况及耐药率,采用Pearson相关性分析方法分析两者之间的关系。结果 6年来我院ICU病房抗菌药物的总用量逐年上升,碳青霉烯类和β-内酰胺/β-内酰胺酶抑制剂的使用量排在前两位。ICU病房分离的排名前3位的革兰阴性菌为鲍曼不动杆菌、肺炎克雷伯菌和铜绿假单胞菌,2018年3种细菌的耐碳青霉烯菌株分离率分别达到了84.62%、53.54%和66.41%。相关性分析显示碳青霉烯类的用量与鲍曼不动杆菌对替加环素的耐药率(r=0.871, P=0.024)及对左氧氟沙星的耐药率(r=0.900, P=0.015)成正相关,与肺炎克雷伯菌对美罗培南(r=0.852, P=0.031)、头孢吡肟(r=0.817, P=0.047)及左氧氟沙星(r=0.857, P=0.029)的耐药率成正相关。结论 广谱抗菌药物的使用与革兰阴性菌的耐药之间存在复杂的相关性,因此应严格控制并合理使用抗菌药物,以延缓细菌耐药的发展。     

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.     

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.