高毒力肺炎克雷伯菌耐药机制研究进展

肺炎克雷伯菌（Klebsiella pneumoniae,KP）是院内感染的常见革兰阴性致病菌;20世纪80年代以来,KP的一种新型变异株-高毒力肺炎克雷伯菌（hypervirulent K.pneumoniae,hvKP）不断产生和蔓延,常感染健康宿主并引起严重的侵袭性感染;早期研究认为高毒力与耐药性不会在同一KP出现,但近期已有hvKP相关菌株耐药甚至多药耐药的报道,耐药性和高毒力的结合可能会成为下一个临床即将面临的重要挑战。现就hvKP耐药报道及相关机制研究进行综述和讨论,希望能为预防和控制耐药hvKP在我国的流行和发展以及为进一步对耐药机制进行深入研究提供参考。     

广东省肇庆市肺炎克雷伯菌临床分离株的耐药性与MLST分型研究

目的 了解广东省肇庆市肺炎克雷伯菌(Klebsiella pneumoniae, KP)临床分离株的抗生素耐药情况及多位点序列分型(multilocus sequence typing, MLST)特征。方法 收集肇庆市两家医院KP临床分离株63株，采用肉汤微量稀释法进行30种抗生素的体外药物敏感性试验，并对所有菌株进行多位点序列分型。结果 63株KP临床分离株的耐药谱特点可分为4类，即全敏感的高毒力肺炎克雷伯菌(hypervirulent K. pneumoniae, hvKP)、产超广谱β-内酰胺酶肺炎克雷伯菌(extended spectrum β-lactamases K. pneumoniae, ESBLsKP)、耐碳青霉烯类肺炎克雷伯菌(carbapenem-resistant K. pneumoniae, CRKP)和其他类型的多重耐药肺炎克雷伯菌(multidrug-resistant K. neumoniae，MDRKP)；MLST分型结果显示63株临床分离株可分成41个ST型。其中，ESBLsKP以ST37型(9株，39.13%)为主，CRKP以ST11型(5株，62.50%)为主，hvKP以ST65(5株，25.00%)型和ST23(3株，15.00%)型为主，而其他类型的多重耐药KP的ST型(12株9种ST型)则呈现明显的多态性。结论 我市肺炎克雷伯菌临床分离株的耐药情况比较严重，要加强院内感染监测，警惕其成为优势菌型并引发院内感染的风险。     

肺炎克雷伯菌的耐药趋势及耐药机制的研究进展

肺炎克雷伯菌(Klebsiella Pneumoniae,KP)是革兰阴性杆菌,是人类呼吸道及肠道的常居菌,可引起呼吸道、消化道、泌尿道、手术伤口等多个部位感染,是医院感染的主要致病菌之一,肺炎克雷伯菌在医院感染中的比重不断上升,不仅出现了对青霉素耐药,而且出现对喹诺酮类抗生素和其他抗生素如头孢菌素类药物等的多重耐药。文章就KP国内外耐药趋势     

血流感染肺炎克雷伯菌中CRISPR-Cas系统的分布及其与毒力基因和耐药的关系

的 了解血流感染肺炎克雷伯菌中CRISPR-Cas系统的分布特征并分析其与毒力基因和耐药的关系。方法 收集非重复血流感染肺炎克雷伯菌248株，使用Vitek2-Compact全自动微生物分析系统进行菌株鉴定及药物敏感性分析，PCR检测CRISPR-Cas系统3个相关基因(CRISPR1、CRISPR2和cas1)、筛查6种常见高毒力荚膜血清型(K1、K2、K5、 K20、K54和K57)、12种毒力基因及检测13种耐药基因，用χ2检验比较携带有CRISPR-Cas系统菌株与不携带CRISPR-Cas系统菌株毒力及耐药差异。结果 CRISPR-Cas系统的检出率为29.8%(74/248)；K1型是携带CRISPR-Cas系统肺炎克雷伯菌的主要荚膜血清型，占 28.4%(21/74)；除kpn基因外，携带CRISPR-Cas系统菌株的毒力基因检出率均大于不携带CRISPR-Cas系统菌株，其中7种差异有统计学意义；除对氨苄西林耐药率达100%外，携带有CRISPR-Cas系统菌株的其他抗菌药物耐药率均小于不携带有CRISPR-Cas系统菌株，其中13种差异有统计学意义；携带CRISPR-Cas系统菌株的耐药基因阳性率小于不携带CRISPR-Cas系统的菌株，且blaKPC、blaSHV、qnrS基因差异有统计学意义。结论 高毒力荚膜血清型肺炎克雷伯菌中主要为K1型携带CRISPR-Cas系统，携带CRISPR-Cas系统的肺炎克雷伯菌相对于不携带CRISPR-Cas系统菌株的毒力基因阳性率高，耐药率低，耐药基因的阳性率低。CRISPR-Cas系统可能能降低耐药基因在肺炎克雷伯菌中的水平传播，尤其是在K1型肺炎克雷伯菌。     

高毒力肺炎克雷伯菌实验室鉴定方法的研究进展

摘要：高毒力肺炎克雷伯菌(hypervirulent Klebsiella pneumoniae, hvKP)具有独特的表型特征和基因型特征，常导致严重的感染。然而，国际上仍无统一的hvKP定义标准，造成不同研究选择的hvKP评价方案不尽相同，基于流行病学分析和感染的快速诊断等多方需求，目前迫切需要关于hvKP的客观鉴定方法。本文从hvKP的表型、毒力基因、毒力评估方面对其实验室鉴定方法进行综述，希望对hvKP的防控提供参考。     

高毒力肺炎克雷伯菌的研究进展

摘要：肺炎克雷伯菌是一种重要的条件致病菌，常引起社区和医院感染。根据毒力的不同，分为高毒力肺炎克雷伯菌和普 通肺炎克雷伯菌。高毒力肺炎克雷伯菌是一种毒力更强的肺炎克雷伯菌进化型，影响其毒力的因素主要包括：荚膜多糖、黏液 表型调控基因、铁载体和可移动的遗传元件等。高毒力肺炎克雷伯菌主要在亚太地区流行，近年来其耐药株分离率明显上升。 本文将对高毒力肺炎克雷伯菌的流行情况、高毒力相关因素、耐药情况及其检测方法作一介绍。     

血流感染肺炎克雷伯菌pLVPK毒力质粒的分布及与耐药的关系

目的 了解血流感染肺炎克雷伯菌中pLVPK毒力质粒的分布情况，分析其与荚膜血清分型及耐药之间的关系。方法 收集医院2016年1月-2017年6月所有非重复血流感染的肺炎克雷伯菌96株，使用Vitek-Compact全自动微生物分析系统进行菌株鉴定及药物敏感性分析；PCR方法检测6种常见高毒力荚膜血清型、7种常见毒力基因、13种常见耐药基因及毒力质粒pLVPK相关基因，使用χ2检验进行统计学分析。结果 血流感染肺炎克雷伯菌株中携带pLVPK毒力质粒率39.6%。其中毒力质粒pLVPK阳性菌株K1荚膜血清分型率显著高毒力质粒pLVPK阴性菌株(P<0.05)，而在其他非高毒力荚膜血清分型上，毒力质粒pLVPK阳性菌株显著低于毒力质粒pLVPK阴性菌株(P<0.05)。pLVPK毒力质粒阳性菌株的毒力基因携带率均显著高于pLVPK毒力质粒阴性菌株(P<0.05)。而pLVPK毒力质粒阳性菌株在耐药性则显著低于pLVPK毒力质粒阴性菌株(P<0.05)，其中pLVPK毒力质粒阳性菌株对blaKPC、blaTEM、blaCTX-M、qnrB及acc(6')-Ib-cr基因的携带显著低于pLVPK毒力质粒阴性菌株(P<0.05)。结论 pLVPK毒力质粒主要集中在K1荚膜血清分型血流感染肺炎克雷伯菌株，pLVPK毒力质粒与毒力基因的携带成正相关，而pLVPK毒力质粒也直接影响了血流感染菌株的耐药性及耐药基因的携带。     

耐碳青霉烯肺炎克雷伯菌耐药机制及治疗策略的研究进展

耐碳青霉烯肺炎克雷伯菌(carbapenem-resistant Klebsiella pneumoniae, CRKP)感染的高发病率和耐药导致的高死亡率是全球所面临的一个重大问题。CRKP耐药形式严峻,导致临床出现可选抗菌药物种类有限、患者住院时间延长及医疗费用剧增等问题,本研究就CRKP的流行病学、耐药机制以及临床治疗等方面进行综述。     

肾移植术后耐碳青霉烯类肺炎克雷伯菌尿路感染治疗实践1例

<正>耐碳青霉烯类肺炎克雷伯菌(carbapenemresistant Klebsiella pneumoniae, CR-KP)易导致败血症、肺炎、尿路感染、软组织感染等感染性疾病,其特征是具有高毒力、高传染性及多重耐药~([1])。CHINET中国细菌耐药性监测数据表明,肺炎克雷伯菌分离株近几年检出率大幅增加,其对亚胺培南和美罗培南的耐药率分别从2005年的3.0%和2.9%上升到了2017年的20.9%和24.0%~([2]),给临床     

血流感染CRKP 的临床特点及高毒力血清型分析

目的 了解耐碳青霉烯肺炎克雷伯菌(carbapenemresistant Klebsiella pneumoniae, CRKP) 血流感染的临床特点及高毒 力血清型的分布情况。方法 收集我院2016 年11 月-2017 年9 月血培养标本分离出的非重复CRKP 22 株，采用美国BD 公司 生产的Phonenix-100 全自动细菌鉴定/ 药敏系统进行菌株鉴定和药敏试验，药敏试验同时联合纸片扩散法(KB 法)，改良Hodge 试验筛查碳青霉烯酶表型。采用PCR 方法及基因测序检测肺炎克雷伯菌的体外溶血酵素基因khe、2 种常见耐药基因(blaKPC 、 blaIMP) 和6 种高毒力血清型(K1、K2、K5、K20、K54、K57)。结果 22 例CRKP 有5 例存活，17 例死亡，死亡率达77.3%；科 室分布主要在重症医学科(59.1%)，神经内科重症病房(22.7%)，泌尿外科(9.1%)，血液科(4.5%) 等。PCR 测序显示22 株CRKP 有17 株检出blaKPC基因，未检出blaIMP基因；高毒力血清型检测结果为K1 型1 株( 占4.5%)，K5 型2 株( 占9.1%)，K20 型2 株( 占9.1%)，主要分布在不携带blaKPC基因的菌株中。22 株CRKP 对亚胺培南和美罗培南的耐药率为100%，对替加环素和多 黏菌素的敏感率高达100%，毒力菌株与非毒力菌株对复方磺胺甲噁唑的耐药率差别不大，分别为60.0% 和52.9%，但对阿米卡 星和庆大霉素的耐药率差别较大，表现为毒力菌株的耐药率低于非毒力菌株。结论 我院流行的CRKP 血流感染菌株主要分离 自重症医学科和神经内科重症病房患者，且死亡率较高；毒力菌株与非毒力菌株对氨基糖苷类抗生素的耐药情况有差别，临床在 治疗过程中应区别对待，并加强防控。     

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.