RNA-acting antibiotics: in-vitro selection of RNA aptamers for the design of new bioactive molecules less susceptible to bacterial resistance

During the last few years, antibiotic multiresistance has been increasing, not only in hospitals, but also, more worryingly, in general medicine. Different ways are being explored to bypass this problem. RNA-acting antibiotics such as aminosides (aminoglycosides) bind to bacterial RNA causing premature termination of proteins and mistranslation in bacteria. It is now possible to study the interactions of such antibiotics with their target by in-vitro selection of RNA molecules that recognize these antibiotics (RNA aptamers, SELEX method). The knowledge of the antibiotic-RNA interactions represents a promising way for the rational design of new bioactive compounds less susceptible to bacterial resistance.     

我院2008-2010年细菌耐药监测及抗菌药物应用分析

目的:了解我院2008-2010年病原菌分布和细菌耐药变迁及抗菌药物应用情况,为临床应用抗菌药物提供参考。方法:回顾性分析我院2008-2010年住院患者病原菌耐药情况及抗菌药物的用药频度(DDDs)。结果:共分离出3185株病原菌,其中革兰阴性菌占55.63%、革兰阳性菌占27.40%、真菌占16.95%,革兰阳性菌和革兰阴性菌的检出率呈逐年上升趋势。以大肠埃希菌、凝固酶阴性葡萄球菌、肠球菌、肺炎克雷伯菌和铜绿假单胞菌最为常见。头孢菌素类、氟喹诺酮类和头霉素类药用量始终位于DDDs排序的前3位。结论:应严格执行《抗菌药物临床应用指导原则》,加强细菌耐药监测工作,根据病原菌种类及药敏试验结果选药。     

我院2006～2008年抗菌药物应用与细菌耐药性分析

目的:了解我院抗菌药物的应用情况及细菌分离和耐药率的变迁特点。方法:调取我院2006～2008年抗菌药物的出库数据,采用限定日剂量法分析抗菌药物的应用情况,同时采用API半自动微生物鉴定系统及药敏卡进行病原菌鉴定及药敏试验。结果:3年中,第1、2代头孢菌素和其它β-内酰胺类抗生素的消耗数量逐年增加,而第3代头孢菌素和含β-内酰胺酶抑制剂复方制剂的应用率逐年降低;同期临床分离的细菌以革兰阴性杆菌为主(占76.2%～78.8%),大肠埃希菌对第3代头孢菌素和含β-内酰胺酶抑制剂复方制剂的耐药率有下降趋势。结论:我院临床分离的革兰阴性杆菌对常用抗菌药物的耐药现象较严重,限制广谱抗菌药物的应用可能减缓细菌耐药趋势。     

Correlation of the antibacterial activities of cationic peptide antibiotics and cationic steroid antibiotics.

The antibacterial activities of cationic steroid antibiotics and cationic peptide antibiotics have been compared. Depolarization of bacterial membranes, activation of bacterial stress-related gene promoters, and changes in bacterial morphologies caused by these antibiotics suggest that cationic steroid and peptide antibiotics share mechanistic aspects. Modified cationic steroid antibiotics display improved selectivity for prokaryotic cells over eukaryotic cells presumably due to increased charge recognition.     

近3年重症监护病房细菌耐药分析

目的了解重症监护病房(ICU)院内感染的流行病学及细菌耐药性变化情况.方法对本院ICU 2001年1月～2003年12月的所有分离菌株进行分析.结果共分离222株细菌,革兰阴性(G-)杆菌共127株(57.21%).革兰阳性(G )菌43株(19.36%).G-杆菌前3位是大肠埃希菌、铜绿假单胞菌、沙雷菌.G 球菌前3位分别是表皮葡萄球菌、金黄色葡萄球菌、粪肠球菌.对第三代头孢菌素耐药率较高,对亚胺培南、万古霉素保持较高的敏感性.结论ICU感染的细菌仍以G-杆菌为主,G 菌感染有上升趋势.细菌耐药率高.应根据细菌耐药监测,指导临床用药,以控制耐药菌的产生.     

Using microarray gene signatures to elucidate mechanisms of antibiotic action and resistance

Microarray analyses reveal global changes in gene expression in response to environmental changes and, thus, are well suited to providing a detailed picture of bacterial responses to antibiotic treatment. These responses are represented by patterns of gene expression, termed expression signatures, which provide insight into the mechanism of action of antibiotics as well as the general physiological responses of bacteria to antibiotic-related stresses. The complexity of such signatures is challenging the notion that antibiotics act on single targets and this is consistent with the concept that there are multiple targets coupled with common stress responses. A more detailed knowledge of how known antibiotics act should reveal new strategies for antimicrobial drug discovery.     

2005～2008年我院抗菌药物使用与细菌耐药性分析

目的：分析抗菌药物使用情况和细菌耐药性的变化趋势,探讨抗菌药物使用频度（DDDs）与细菌耐药性之间的关系,为临床合理应用抗菌药物提供参考依据。方法：统计我院2005～2008年的相关数据资料,分析抗菌药物使用情况和细菌耐药性,分析用药频度与细菌耐药性之间的相关性。结果：头孢菌素类抗菌药物4年来DDDs一直处于第1位,临床用药选择倾向于价格更高、抗菌谱广的2线抗菌药物。DDDs排序前列的药物,耐药率普遍较高。临床分离的细菌以革兰阴性杆菌为主,第3代头孢菌素对铜绿假单胞菌的耐药率应引起临床注意。万古霉素对表葡菌和金葡菌的耐药率最低。氟康唑对白色念珠菌的耐药率多年来居高不下。部分抗菌药物的DDDs与细菌耐药率呈显著正相关关系。结论：应多方并举加强抗菌药物管理,合理使用抗菌药物,减少细菌耐药性的发生,提高临床抗感染治疗的效果。     

Studies on the synergism of sulbactam and beta-lactam antibiotics under in vitro conditions and in healthy volunteers after intravenous administration. Antibacterial activity in vitro, compatibility and pharmacokinetics of the drugs in combination

Sulbactam, a new beta-lactam inhibitor, increased the in vitro activity of cefotaxime, mezlocillin and piperacillin against 803 clinical bacterial isolates. The synergism of sulbactam and these antibiotics was particular marked against 467 beta-lactamase positive strains, both aerobic and anaerobic. In the presence of sulbactam the mean minimal inhibitory concentrations (MICs) of the antibiotics against beta-lactamase positive bacteria were greatly reduced: with cefotaxime by 58%, with mezlocillin by 64% and with piperacillin by 70%. Sulbactam alone at low concentrations inhibited the growth of only a few strains (Neisseria spp., Acinetobacter spp.). The inhibitor proved to be very stable in infusion media under a variety of conditions and was compatible in vitro with 14 different beta-lactam antibiotics. The pharmacokinetics profiles of sulbactam and the antibiotics cefotaxime, mezlocillin and piperacillin were similar after infusion to healthy volunteers. The relevant pharmacokinetic parameters of the single substances were essentially unchanged when administered in combination. The general similarity between the pharmacokinetics of sulbactam and of the beta-lactam antibiotics appears to be an essential precondition for the therapeutic success of such a synergistic combination. Thus the physicochemical and pharmacological properties of sulbactam apparently permit flexible dosage in combination with different penicillins or cephalosporins and sulbactam can be administered as non-fixed combination in the clinical treatment of bacterial infections.     

β-内酰胺类抗生素使用情况及细菌耐药性分析

目的 分析某院β-内酰胺类抗生素的使用及病原菌耐药情况,为临床合理用药提供参考依据.方法 统计分析某院2008年1月至2009年12月β-内酰胺类抗生素的用药频度(DDDs)、总消耗金额、日治疗费用(DDC)和病原菌耐药率.结果 调查期内β-内酰胺类抗生素中头孢菌素类抗生素使用最为广泛;青霉素钠的日治疗费用最低,序号比最大;大多数抗生素在调查期内耐药率的差异不显著,但均产生不同程度的耐药率.结论 某院β-内酰胺类抗生素应用存在不合理现象,应加强抗生素的监管及用药前的药敏监测以减少抗生素不合理使用.     

抗感染性药物用于非感染性疾病治疗的弊端

目的呼吁严格限制抗微生物药物用于治疗非感染性疾病。方法根据抗微生物药物临床应用的相关报道,分析存在的弊与利、害与益。结果抗微生物药物在治疗非感染性疾病时,其杀菌和抑菌作用即成为治疗中的不良反应,不仅会破坏患者个体体内正常寄生菌群的平衡,引起继发感染;而且其广泛性和长期性的用药特点,将导致耐药性微生物的产生和发展。结论非感染性疾病的治疗有许多其他有效的药物,并非到了不用抗微生物药物不可的地步,因此应该把遏制微生物耐药性、保护现有抗微生物药物资源作为首要任务。     

中医护理干预对细菌性肝脓肿的疗效观察

目的探讨中医护理干预对细菌性肝脓肿患者的疗效。方法对60例肝脓肿患者分成对照组、干预组,对照组采用经B超引导下经皮肝脓肿穿刺置管引流术,术后根据脓液细菌培养采取敏感抗生素加支持治疗,术前、术后按疾病常规及医嘱进行护理,干预组在对照组基础上术前、术中、术后均实施中医护理干预。结果干预组住院日<15d例数明显高于对照组,出院后的复发率明显低于对照组。结论中医护理干预对肝脓肿患者的治疗有确切的疗效。     

Patents on streptogramin antibiotics

Streptogramin represents a unique class of antibiotics remarkable for their antibacterial activity and their unique mechanism of action. The streptogramin antibiotics are a family of natural products that have been isolated from strains of Streptomyces found in soil organisms. This review summarises patents claiming streptogramin antibiotics published from January 1999 to December 2002. The majority of the patents described here disclose chemistry and biological evaluation of new streptogramin derivatives. In general, streptogramins have demonstrated activity against Gram-positive microorganisms in vitro and in vivo, including those with multi-drug resistance. Moreover, the absence of cross-resistance to macrolides in many of these microorganisms, and the rarity of cross-resistance between the two groups of antibiotics associated with rapid bacterial killing, are the principal features of the streptogramins. This indicates an important possible role in treating the rising number of infections that are caused by multiple-resistant Gram-positive bacteria.     

某三级甲等综合性医院抗菌药合理应用干预与成效分析

摘 要 目的：分析某三甲综合性医院抗菌药临床应用情况,考察该院抗菌药的合理应用干预成效。方法：采取回顾性调查方法,通过医院信息管理系统及抗菌药专项点评等方式,调取该院干预前（2010年）、干预强化期（2011~2013年）、干预后（2014~2015年）抗菌药临床应用信息,对抗菌药使用率、抗菌药使用强度（AUD）及其使用合理率、病原微生物送检率及其耐药率等进行统计分析。结果：通过对抗菌药合理应用进行干预,该院抗菌药使用率、AUD等使用指标改善,均有效控制在国家规定范围内,抗菌药使用合理性有提高,病原微生物送检率逐年上升,细菌耐药率在干预强化期明显降低,但2015年,鲍曼不动杆菌和肺炎克雷伯杆菌的耐药率有反弹现象,白色念珠菌取代金黄色葡萄球菌进入医院前5位的病原微生物中。结论：抗菌药合理应用干预成效显著,但仍有待加强对抗菌药合理使用的管理能力。     

细菌对MLS类和糖肽类抗生素产生耐药性的作用机制

MLS类和糖肽类抗生素在人类与细菌感染性疾病的对抗中发挥着重要作用.与其他抗生素一样,随着这些抗生素的临床使用,细菌耐药性的出现和不断发展给人们带来新的挑战.本综述对这两类抗生素的细菌耐药性产生机制进行了剖析,并就已开发的若干个新型MLS类和糖肽类抗生素作了介绍.     

我院2007年细菌性上呼吸道感染患者抗菌药物使用分析

目的了解细菌性上呼吸道感染患者抗菌药物分级使用情况。方法抽取2007年相关病历627份,对照抗菌药物使用管理规定分析其合理性。结果二线抗菌药物使用率为28．23％,细菌学检查率为87．01％。结论细菌性上呼吸道感染患者抗菌药物使用基本合理。     

8种头孢类抗菌药物无菌检查的方法学验证研究

目的:建立8种头孢类抗菌药物的无菌检查方法,并进行方法学验证。方法:采用薄膜过滤法,以每筒300或500mL冲洗量,加入150万u·100mL-1或300万u·100mL-1的青霉素酶以消除抗菌药物的抑菌活性,分别设立试验组(样品+青霉素酶)、试验菌阳性对照组(阳性菌)、样品组(样品+阳性菌)和阴性对照组(稀释液)进行试验,观察各组菌生长情况。结果:样品组和阴性对照组均未见菌生长,所有阳性对照组及试验组菌在冲洗量为每筒300mL、加酶量每筒300万u的条件下,均在2d内菌生长良好。结论:对头孢类抗菌药物进行无菌检查时,将其制备成一定浓度后按薄膜过滤法操作,再加入青霉素酶每筒300万u、冲洗量每筒300mL,可以消除抗菌药物的抑菌活性对检查带来的干扰。     

烧伤创面细菌培养及药敏分析

目的分析烧伤创面分泌物的细菌检出率及耐药性。方法烧伤患者112例创面采集标本212份,用普通细菌培养方法,进行培养、分离、鉴定,做细菌药敏和细菌耐药试验。结果 212份标本中细菌生长阳性138份(65.09%),其中以金黄色葡萄球菌(27.54%)和铜绿假单胞菌(24.64%)为主,且耐药性较高。金黄色葡萄球菌对头孢噻肟敏感性最高(54.4%),铜绿假单胞菌对阿米卡星敏感性最高(70.2%)。结论应及早进行创面细菌培养,根据细菌和药敏试验结果合理选择使用抗生素。     

从细菌药敏结果动态观察看临床用药指引

目的针对本院近两年临床常见致病菌的耐药情况,提出临床经验性的抗菌药物的用药指引。方法采用回顾性分析方法采集2006～2007年细菌分布情况和药敏数据,将数据进行对比分析。结果临床应了解细菌耐药特点,掌握适应症。结论通过了解细菌对抗菌药物的敏感性及耐药变异情况,可提供有别传统抗菌药物用药依据的用药指引,合理选用抗菌药物。     

我院2008～2010年抗菌药应用与细菌耐药性分析

目的：了解我院抗菌药的应用情况及细菌分离和耐药的变迁特点。方法：调取我院2008～2010年抗菌药的出库数据,采用限定日剂量法分析抗菌药的应用情况,同时采用API半自动微生物鉴定系统及药敏卡进行病原菌鉴定及药敏试验。结果：喹诺酮类和大环内酯类的用药频度逐年增加,第2、4代头孢菌素的用药频度也呈现逐年增加趋势,广谱青霉素、第1、3代头孢菌素和含B内酰胺酶抑制药复方制剂的用药频度保持平稳。同期分离的细菌中,大肠埃希菌对喹诺酮类的耐药率逐年递增,葡萄球菌对大环内酯类耐药比较严重,需引起重视.结论：我院临床分离的细菌的耐药现象比较严重,应限制广谱抗菌药的应用,以延缓细菌耐药趋势.