家蝇抗菌肽分子结构及抗菌谱研究

目的研究家蝇抗菌肽的分子结构和抗菌谱,寻找广谱高效天然抗菌肽。方法家蝇被损伤感染诱导免疫后制成组织匀浆,用蛋白质纯化技术分离纯化抗菌肽,测定抗菌活性及抗菌谱,纳升电喷雾飞行时间质谱测定氨基酸序列。结果家蝇组织提取液经蛋白质纯化,得到一纯化的抗菌活性成份,纳升电喷雾飞行时间质谱测序,得到两个肽段的氨基酸序列:肽段1.QPNLYYNK和肽段2.PNNVYYTK。通过NCBInr蛋白质数据库检索,未发现有与之序列相匹配的蛋白质。该抗菌肽对11种临床标本分离菌株铜绿色假单胞菌、大肠埃希菌、伤寒沙门菌、普通变形菌、异形柠檬酸杆菌、肺炎克雷伯菌、阴沟肠杆菌、福氏痢疾杆菌、表葡菌、耐甲氧西林金葡菌(MRSA)和白念珠菌的MIC分别为:3.89、2.22、4.44、6.67、3.33、6.67、5.0、6.67、4.44、4.44和13.33μmol/L。结论本文得到的抗菌肽是一个新型抗菌肽,有广谱抗菌活性,对革兰阴性菌和革兰阳性菌均有一定的抑制作用。     

家蝇幼虫抗菌活性诱导研究

目的探讨针刺损伤方法对家蝇幼虫抗菌肽类物质诱导表达的影响,并对所得抗菌肽粗提液的保存条件进行了研究。方法人工饲养的家蝇5日龄幼虫,针刺损伤体壁后,制备抗菌肽粗提液,分别置4℃和-20℃保存30d,BCA蛋白测定试剂盒测定蛋白含量。并以大肠埃希菌为指示菌,琼脂打孔扩散法抑菌试验检测抗菌活性大小。结果针刺损伤诱导后提取的抗菌肽粗提液对大肠埃希菌的抑菌活性高于未诱导组,粗提液于4℃保存比-20℃保存更有利于抗菌肽的活性保持。结论针刺损伤法可诱导家蝇幼虫产生抗菌肽类物质,抗菌肽粗提液置于4℃保存更有利于抗菌肽活性的保持。     

烯二炔类大分子抗肿瘤抗生素C1027抗菌与抗肿瘤活性差异的研究

Ｃ１０２７具有极强杀伤肿瘤细胞活性,作用靶点在ＤＮＡ,但Ｃ１０２７ 的抗菌活性不强,如能了解差别出现的原因,就可进一步掌握Ｃ１０２７的抗菌作用机制,并为将来在临床上确定其应用范围打下良好基础。对Ｃ１０２７ 的抗肿瘤活性与抗菌活性的差异的初步研究结论如下：大分子Ｃ１０２７ 与小分子博莱霉素Ａ５ 相比,对肿瘤细胞抑制作用明显高于后者;对细菌的抑制作用却明显低于博莱霉素Ａ５;对支原体的抑制作用略大于博莱霉素Ａ５ 。Ｃ１０２７（１００～０．０１ｍ ｇ／Ｌ）对大肠埃希氏菌Ｂ原生质体ＤＮＡ合成几乎无抑制作用,同对大肠埃希氏菌Ｂ菌体的ＤＮＡ合成抑制作用相比,差别不大。细胞壁并非阻碍Ｃ１０２７损伤大肠埃希氏菌ＢＤＮＡ的主要因素。     

头孢唑肟与其他5种抗生素体外抗菌活性比较

目的　比较头孢唑肟与其他 5种抗生素对临床分离菌的体外抗菌活性。方法　用 NCCL S2 0 0 2年发布的琼脂平板法测定抗生素的最低抑菌浓度。结果　本研究共测定细菌 5 70株 ,其中革兰氏阴性菌 36 7株 ,革兰氏阳性菌 2 0 3株。头孢唑肟对肠杆菌科细菌与链球菌具有强大抗菌活性 ,大肠埃希氏菌、肺炎克雷伯氏菌、产气肠杆菌、志贺氏菌、奇异变形菌、摩根摩氏菌、流感噬血杆菌、肺炎链球菌、化脓链球菌、无乳链球菌、粘膜炎莫拉氏菌对头孢唑肟 10 0 %敏感。头孢唑肟对大多数肠杆菌科细菌 MIC值与头孢曲松相近 ,远低于头孢他啶和头孢呋辛。头孢唑肟对液化沙雷氏的菌抗菌活性为所有检测药物中最强的一个 ,MIC50 与 MIC90 均为0 .5 mg/ L。结论　头孢唑肟应用于临床 15年后仍保持强大抗菌活性 ,本品可用于中重度细菌感染的经验性治疗     

三种碳青霉烯类抗生素对ICU分离菌株的体外抗菌作用

为评价亚胺培南、帕尼培南与美罗培南的体外抗菌作用,用琼脂双倍稀释法测定从我院重症监护病房分离的230株革兰氏阴性菌的最低抑菌浓度（MIC）,并采用抑制剂增强的纸片扩散法测定大肠埃希氏菌和肺炎克雷伯氏菌超广谱β－内酰胺酶（ESBLs)。结果,50株肺炎克雷伯氏菌和17株大肠埃希氏菌中的ESBLs阳性率为61．2％。三种碳青霉烯类对阴沟肠杆菌、肺炎克雷伯氏菌、大肠埃希氏菌、不动杆菌等都具有高度的抗菌活性,且对产ESBLs菌株保持高度的抗菌活性。对嗜麦芽黄单胞菌高度耐药。提示碳青霉烯类抗生素是重症监护病人多重耐药菌感染的良好选择。     

国产甲磺酸左氧氟沙星体外抗菌活性研究

测定国产甲磺酸左氧氟沙星体外抗菌活性,并与进口左氧氟沙星作比较,以临床常用的氧氟沙星和环丙沙星为对照。结果表明,国产甲磺酸左氧氟沙星与进口左氧氟沙星体外抗菌活性无差异。甲磺酸左氧氟沙星抗菌谱广抗菌活性强,对革兰氏阴性肠道杆菌、肺炎克雷伯氏菌、肠杆菌属细菌、变形杆菌及嗜血杆菌和不动杆菌ＭＩＣ５０值是氧氟沙星的１／２,与环丙沙星一致,分别为＜０．０３、＜０．０３、＜０．０３、０．１２５和０．０３ｍｇ／Ｌ;它对大肠埃希氏菌、金葡球菌、肺炎链球菌、肠球菌、厌氧菌的ＭＩＣ５０值是氧氟沙星和环丙沙星的１／２～１／４;对铜绿假单胞菌ＭＩＣ５０为１ｍｇ／Ｌ,是氧氟沙星的１／２,但稍高于环丙沙星。该产品体外抗菌活性受细菌接种量、血清含量和ｐＨ值影响不明显。研究还表明该产品为一杀菌剂,对临床常见致病菌如大肠埃希氏菌、肺炎克雷伯氏菌、变形杆菌、铜绿假单胞菌、不动杆菌、葡萄球菌、肠球菌、肺炎链球菌、厌氧菌均有良好的杀菌作用。     

阳离子多肽MP-1的抗菌作用研究

目的　观察阳离子多肽 Mastoparan- 1(MP- 1)的体内、外抗菌作用。方法　采用微量稀释法观察MP- 1对 18株细菌的最低抑菌浓度 (MIC)和最低杀菌浓度 (MBC) ;将 MP- 1(10 0 μg/ml)与大肠埃希氏菌ATCC2 5 92 2 37℃共孵育 5、10、15 min,透射电镜下观察细菌形态的变化 ;应用生物传感器检测 MP- 1与内毒素 (L PS)及其活性中心类脂 A(L ipid A)结合的亲和力 ;以 ATCC2 5 92 2活菌攻击小鼠 (2× 10 9CFU/2 0 g体重 ) ,观察 MP- 1(3mg/kg)对小鼠的保护作用。结果　MP- 1具有一定的体外抗菌活性 ;MP- 1与细菌作用 5 min时 ,细菌外膜粗糙 ,内膜轮廓模糊 ,10 min时胞质不均匀 ,可见空泡 ,15 min时菌体肿胀 ,胞内空泡变性明显加重 ;MP- 1对 L PS/L ipid A均具有较高的亲和力 ;MP- 1可显著提高活菌攻击小鼠的 3天存活率。结论　MP- 1对革兰氏阴性菌及革兰氏阳性菌均具有一定的抗菌作用 ,它对大肠埃希氏菌 ATCC2 5 92 2的杀菌活性可能与其对细菌细胞膜破坏、通透性增加有关 ,此特性可能基于 MP- 1与细菌外膜 L PS/L ipid A的结合作用实现。     

复方紫柄冬青软膏对烧烫伤细菌感染的体外抗菌活性研究1

目的：评价复方紫柄冬青软膏对临床常见菌种的抗菌活性。方法：采用中药抑菌实验方法,测定复方紫柄冬青软膏对3种实验菌（金黄色葡萄球菌、大肠埃希菌、铜绿假单胞菌）的体外抗菌活性。结果：经体外抗菌实验,其结果显示复方紫柄冬青软膏中含生药125（高浓度）,62．50（中浓度）和15．62mg／mL（低浓度）的样品溶液,其高浓度对3种实验菌株均有抑制作用,中浓度对大肠埃希菌和铜绿假单胞菌有抑制作用,而低浓度仅对大肠埃希氏菌有抑制作用。结论：复方紫柄冬青软膏对金黄色葡萄球菌、大肠埃希菌、铜绿假单胞菌均有不同程度的抑菌活性。     

血液病区抗菌药物用量与大肠埃希氏菌耐药的相关性分析

目的探讨2005—2007年血液病区抗菌药物使用量与大肠埃希氏菌耐药水平变化之间的关系。方法计算7种抗菌药物平均每日每百张床位所消耗的DDDs及同期大肠埃希氏菌的耐药率,并对抗菌药物用量与耐药率进行相关性分析。结果哌拉西林-他唑巴坦的使用量与大肠埃希氏菌对头孢他啶和头孢吡肟的耐药率呈显著负相关性：头孢曲松的使用量与大肠埃希氏菌对阿米卡星的耐药率呈显著相关性;而左氧氟沙星的使用量又与大肠埃希氏菌对头孢曲松的耐药率呈显著相关性。结论血液病区适当增加哌拉西林-他唑巴坦的使用,可以减少大肠埃希菌对第三代头孢菌素的耐药率。     

血液病区抗菌药物用量与大肠埃希氏菌耐药的相关性分析

目的探讨2005~2007年血液病区抗菌药物使用量与大肠埃希氏菌耐药水平变化之间的关系。方法计算7种抗菌药物平均每日每百张床位所消耗的DDDs及同期大肠埃希氏菌的耐药率,并对抗菌药物用量与耐药率进行相关性分析。结果哌拉西林-他唑巴坦的使用量与大肠埃希氏菌对头孢他啶和头孢吡肟的耐药率呈显著负相关性;头孢曲松的使用量与大肠埃希氏菌对阿米卡星的耐药率呈显著相关性;而左氧氟沙星的使用量又与大肠埃希氏菌对头孢曲松的耐药率呈显著相关性。结论血液病区适当增加哌拉西林-他唑巴坦的使用,可以减少大肠埃希菌对第三代头孢菌素的耐药率。     

Innovation in infectious disease therapies from immunology

Antimicrobial therapies developed from immunology, specifically the primary function of the immune system in host defence against microbial pathogens, could offer some of the step-change strategies in drug design and development urgently required to generate much needed, truly novel interventions in infectious disease. The immune system is an as yet underexploited resource of novel molecules and the blueprints for new approaches to combating infection with non-antibiotic, directly antimicrobial strategies.     

1332株葡萄球菌的标本分布及耐药性分析

目的了解我院葡萄球菌的临床分布及对常用药物的耐药性,为临床控制感染及经验用药提供有力依据。方法收集2011-2013年我院分离的葡萄球菌,采用西门子Micro Scan Walk Away40SI全自动细菌鉴定药敏分析系统进行鉴定和药敏试验,结果按CLSI M100-S23进行判断,采用WHONET 5.6软件进行统计分析。结果 3年中共检出葡萄球菌1 332株,MRSA和MRCo NS的发生率分别为51.7%(372/720)和80.4%(492/612),未发现对万古霉素、利奈唑胺和达托霉素耐药的葡萄球菌。结论我院相关结果与全国耐药监测数据比较,有地区性差异,只有不断提高监测水平,合理选用抗菌药物,才能减少耐药菌的发生。     

Cathelicidins抗菌肽家族的研究进展

Cathelicidins是一族在哺乳动物中发现的含有保守的cathelin区域的抗菌肽，是宿主防御系统的重要组成部分，具有广谱且强大的抗菌活性。文章综述了cathelicidins抗菌肽家族的基因组成、结构、抗菌活性、作用机制及构效关系等。     

安徽省淮南地区鲍曼不动杆菌耐药性检测

目的 了解淮南地区临床分离鲍曼不动杆菌对临床常用抗生素的耐药性,指导临床合理使用抗生素.方法 选择淮南地区3家医院2010年10月至2012年6月临床分离鲍曼不动杆菌160株,应用生物梅里埃公司的VITEK32全自动微生物分析系统进行细菌鉴定和药物敏感试验,头孢哌酮/舒巴坦药敏试验使用纸片扩散法检测.结果 鲍曼不动杆菌对10种抗菌药物耐药率高于50.0％,其中对氨曲南的耐药率达到90.1％;仅对4种抗菌药物耐药率低于50.0％,其中对头孢哌酮/舒巴坦耐药率最低,为23.4％,其次为亚胺培南和美罗培南,耐药率分别为26.0％和31.2％.结论 淮南地区临床分离的鲍曼不动杆菌耐药和多重耐药现象严重,头孢哌酮/舒巴坦和亚胺培南可做为临床鲍曼不动杆菌感染治疗的首选药物.     

1000株肠球菌耐药性分析

目的 测定1999年1月至2002年12月临床分离的1000株肠球菌对11种抗生素的敏感性现状，为临床合理选药提供客观实验依据。方法 菌株经Vitek和Microscan及常规方法鉴定，按照NCCLS推荐的纸片扩散法和判断标准进行药敏试验，并用WHONET5软件进行分析，用琼脂稀释法测定菌株的MIC值。结果 粪肠球菌和屎肠球菌分离率分别占肠球菌的56．0％和41．7％；居前4位的标本依次是尿液(68．7％)、痰液(15．3％)、血液(8．3％)、脓性分泌物(6．4％)。纸片法测定结果表明粪肠球菌和尿肠球菌对万古霉素、呋喃妥因、氯霉素、红霉素、四环素、青霉素、氨苄西林、亚胺培南、高浓度庆大霉素以及环丙沙星的耐药率分别为2．2％、3．3％；10．0％、12．7％；54．5％、73．8％；82．3％、96．8％；43．3％、44．7％；17．1％、85．9％；14．9％、73．9％；13．8％、72．5％；46．0％、55．4％；34．8％、66．9％。MIC值测定结果表明头孢硫脒对粪肠球菌MIC50和MIC90分别为2和16mg／L；对屎肠球菌为16和128mg/L。万古霉素对粪肠球菌、屎肠球菌MIC50、MIC90均为2和4mg／L。结论 肠球菌对万古霉素耐药率低，头孢硫脒与其它药物相比对粪肠球菌体外活性较强，对屎肠球菌活性相当，肠球菌对其余9种抗菌药物耐药率有逐年增加的趋势。     

Antimicrobial activity and durability of a novel antimicrobial-impregnated bladder catheter

The main objective of this study was to examine the antimicrobial activity and durability of a novel indwelling bladder catheter impregnated with minocycline and rifampin. Thirty antimicrobial-impregnated bladder catheters were inserted transurethrally in spinal cord-injured patients and removed, in six groups of five catheters each, at 3, 7, 10, 14, 17 or 21 days. Removed catheters had detectable zones of inhibition against two different clinical isolates of each of the 10 tested uropathogens (Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter diversus, Enterococcus faecalis, Enterococcus faecium, Staphylococcus saprophyticus and Candida albicans) for greater than 14 days after catheter insertion. The residual zones of inhibition and levels of antimicrobial agents in removed catheters were both inversely related to the duration of catheter placement. Minocycline and rifampin were undetectable in serum and urine. These results support the ongoing efforts for examining the clinical efficacy of these experimental bladder catheters.     

Implementation and outcomes of a hospital-wide computerised antimicrobial stewardship programme in a large medical centre in Taiwan

Antibiotic stewardship is important to address the problem of antimicrobial resistance, but a practical and sustainable strategy to provide stewardship in a large hospital setting is lacking. We developed a hospital-wide computerised antimicrobial approval system (HCAAS) to guide the use of antimicrobial agents in late 2004 in a 3500-bed medical centre in Taiwan. The objective of this study was to evaluate the impacts of HCAAS on the hospital from 2003 to 2009. Following HCAAS deployment, the gradients of consumption over time during the study period of third- and fourth-generation cephalosporins, fluoroquinolones and glycopeptides fell significantly, whilst that of carbapenems increased. The amount and expenditure of antimicrobial use did not increase with the overall healthcare-associated infection rate, and inpatient mortality rate remained stable with a slight decreasing trend. The rate of meticillin-resistant Staphylococcus aureus started to decline in 2002 and continued after HCAAS deployment. There was an increasing isolation of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae, presumably leading to the increased use of carbapenems. The isolation rate of Clostridium difficile from patients who developed diarrhoea after antimicrobial therapy did not change over the years, with a mean annual rate of 10.0% after the implementation of HCAAS. HCAAS along with strict infection control measures is necessary to reduce the spread of resistant organisms within the hospital. HCAAS is a sustainable system for providing antibiotic stewardship and exerts a positive impact on the hospital by reducing antimicrobial consumption and expenditure whilst not compromising healthcare quality.     

Experiences and perspectives of implementing antimicrobial stewardship in five French hospitals: a qualitative study

The aim of this study was to describe current antimicrobial stewardship programmes (ASPs) in France, both at policy level and at local implementation level, and to assess how ASP leaders (ASPL) worked and prioritised their activities. A qualitative study based on face-to-face semi-structured interviews with healthcare professionals responsible for ASPs across five French hospitals was conducted. Five infectious diseases specialists and one microbiologist were interviewed between April–June 2016. Stewards had dedicated time to perform ASP activities in two university-affiliated hospitals, whilst in the other hospitals (one university, one general and one semi-private), ASPLs had to balance these activities with clinical practice. Consequently, they had to adapt interventions according to their resources (IT or human). Responding to colleagues' consultation requests formed baseline work. Systematic and pro-active measures allowed for provision of unsolicited counselling, whilst direct counselling on wards required appropriate staffing. ASPLs aimed at increasing clinicians' ability to prescribe adequately and awareness of the unintended consequences of inappropriate use of antibiotics. Thus, persuasive, e.g. education, measures were preferred to coercive ones. ASPLs faced several challenges in implementing the ASP: overcoming physicians' or units' reluctance; and balancing the influence of medical hierarchy and professional boundaries. Beyond resources constraints, ASPLs' conceptions of their work, as well as contextual and cultural aspects, led them to adopt a persuasive and collaborative approach of counselling. This is the first qualitative study regarding ASPs in France exploring stewards' experiences and points of view.     

国外抗菌药物管理项目实施经验及启示

抗菌药物管理项目（antimicrobial stewardship programs,ASP）是在医疗机构实施的综合性管理项目,用来提高抗菌药物的使用合理性,并预防和控制耐药性的产生.自20世纪90年代,欧美许多国家就已开展了ASP,并取得了成效.本文总结了国外ASP实施的一些成功经验,提出对我国抗菌药物管理的启示和建议.