抗革兰氏阳性菌感染药物的研究进展

革兰氏阳性菌的多重耐药性问题日益严重,临床迫切需要新的抗菌药物。寻找对革兰氏阳性菌有效的药物是当今抗感染药物研究的一个热点。本文简要综述近５年来抗革兰氏阳性菌感染药物研究的进展和动向,介绍对革兰氏阳性耐药菌有显著活性或疗效的药物,特别是一些新结构类型的化合物：■唑烷酮类化合物,甘氨酞环素,酮内酯类化合物,糖肽类抗生素,链阳菌素,２－吡啶酮类化合物和喹诺酮类药物。     

抗草兰氏阳性菌感染药物的研究进展

革兰氏阳性菌的多重耐药性问题日益严重，临床迫切需要新的抗菌药物。寻找对芏兰氏阳性菌有效的药物是当今抗感染药物研究的一个热点。本文简要综述近５年来抗革兰氏阳性菌感染药物研究的进展和动向，介绍对芏兰氏阳性耐药菌有显著活性或疗效的药物，特别是一些新结构类型的化合物：恶唑烷酮类化合物，甘氨酰环素，酮内酯类化合物，糖肽类抗生素，链阳菌素，２－吡啶酮类化合物和喹诺酮类药物。     

抗革兰氏阳性菌感染药物的研究进展

近年来致病菌的多重耐药性已严重影响抗菌药的临床疗效，成为人们关注和研究的热点之一。其中革兰氏阳性菌耐药性问题尤为突出，以葡萄球菌、链球菌和肠球菌的耐药性最为常见和严重。目前抗革兰氏阳性菌药物相对比较缺乏，为了更有效地解决耐药性问题，当务之急就是寻找并开发新型有效的抗菌药。介绍近3年来抗革兰氏阳性菌药物的研究进展。     

抗革兰氏阳性菌感染的新药Daptomycin

对热性中性白细胞减少症的疗效 :10名免疫缺陷患有热性中性粒细胞减少症并由耐万古霉素粪肠球菌引起的感染患者 ,在一项开放Ⅱ期临床对照试验中证明Ｄａｐｔｏｍｙｃｉｎ更有效。这些患者或在近期接受了骨髓移植或患有急性髓细胞白血病 ,并均患有由耐万古霉素肠球菌引起的菌血症 ;这种感染的患者通常很难预后。给予Ｄａｐｔｏｍｙｃｉｎ 6ｍｇ/ (ｋｇ·ｄ) ,疗程平均 14ｄ(3～ 18ｄ)。对这 10名患者 (8名男性 ,2名女性 )进行了应答评价 ,其中 5名接受了骨髓移植 ,6名患有急性白血病。在这 10名患者中由耐万古霉素粪肠球菌引起的中性白细胞减…     

利奈唑胺治疗革兰氏阳性菌导管相关性菌血症的临床评价

目的：评估利奈唑胺治疗革兰氏阳性菌导管相关性菌血症的疗效和安全性。方法以2009年1月-2013年10月在我院重症医学科住院、确诊为革兰氏阳性菌导管相关性菌血症的患者为研究对象,随机分成两组（利奈唑胺组和万古霉素组）,分别予利奈唑胺注射液600mg或万古霉素注射液1.0g静脉滴注,每12h 1次,连用14d,比较两种药物的临床疗效及不良反应。结果利奈唑胺组退热时间较万古霉素组短（P〈0.05）;两组痊愈率、有效率、细菌清除率无统计学差异（P〉0.05）;治疗前后两组的白细胞计数、中性粒细胞比例、C-反应蛋白、降钙素原均下降,但两组比较无显著性差异（P〉0.05）;利奈唑胺不良反应少于万古霉素（P〈0.05）。结论利奈唑胺治疗革兰氏阳性菌导管相关性菌血症疗效显著,安全性好。     

湖北地区革兰氏阳性球菌耐药现状与变迁

湖北地区自1996年开始细菌耐药性监测，革兰氏阳性球菌分离率逐年升高，近年二、三级医院均达40％，以凝固酶阴性葡萄球菌居首位。MRSA5年上升14％，医院问差异明显；VRE分离率为2％～3％，以VanB型为主；PISP PRSP分离率为41．6％，其中儿童为65％。SMZ/TMP与氯霉素对金黄色葡萄球菌的耐药率似呈下降趋势，而庆大霉素、环丙沙星、四环素、红霉素、克林霉素的耐药率显著上升。二级医院MRSA平均为8．6％。     

抗革兰氏阳性菌抗生素药效学研究

抗生素药效学研究对揭示药物抗菌效果、制定给药方案、指导临床合理用药、防止细菌耐药产生等有重要价值 ,PK/PD研究已成为新药开发必不可少的内容。抗革兰氏阳性菌抗生素药效学研究涉及药物体内外抗菌活性、抗菌作用动力学、细菌耐药等 ,参数有MIC、MBC、T >MIC、Cmax/MIC等 ,本文简要介绍 β -内酰胺类、氨基糖苷类、喹诺酮类、大环内酯类以及糖肽类药物药效学研究。     

利奈唑胺治疗儿童革兰氏阳性菌感染疗效的Meta分析

目的采用Meta分析比较利奈唑胺和万古霉素(或头孢羟氨苄)治疗儿童革兰氏阳性菌感染的临床疗效。方法检索Medline数据库、Embase数据库、Ovid数据库、Cochrane图书馆及中文生物医学期刊数据库等,收集利奈唑胺治疗儿童革兰氏阳性菌感染的随机对照试验文献,对照组为万古霉素或头孢羟氨卞,采用RevMan 5.0进行统计分析。结果共纳入合格文献5篇,患者1164例。利奈唑胺组临床治愈率与对照组相当[OR=1.54,95%CI(1.01-2.35),P=0.05];利奈唑胺组微生物清除率与对照组相当[OR=1.07,95%CI(0.62-1.83),P=0.81];利奈唑胺组不良反应少于对照组[OR=0.53,95%CI(0.33-0.86),P=0.01]。结论利奈唑胺疗效肯定,安全可靠。     

噁唑烷酮类抗菌剂构效关系及结构改造研究进展

噁唑烷酮类抗菌药是一类结构类型与作用机制完全不同于目前其他所有抗菌药物的新型合成抗菌药,自首个该类药物利奈唑胺上市后,以获得抗菌谱更广、抗菌活性更高的新型噁唑烷酮类化合物为目标的结构改造方案及有关细菌对化合物耐药机制的研究便全面展开。综述噁唑烷酮类抗菌药的作用机制、构效关系、细菌对其的耐药机制和相关的化合物结构改造的研究进展。     

Novel antibacterial agents for the treatment of serious Gram-positive infections

With the continuing development of clinical drug resistance among bacteria and the advent of resistance to the recently released agents quinupristin-dalfopristin and linezolid, the need for new, effective agents to treat multi-drug-resistant Gram-positive infections remains important. This review focuses on agents presently in clinical development for the treatment of serious multidrug-resistant staphylococcal, enterococcal and pneumococcal infections, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and penicillin-resistant Streptococcus pneumoniae. Agents to be discussed that affect the prokaryotic cell wall include the antimethicillin-resistant S. aureus cephalosporins BAL9141 and RWJ-54428, the glycopeptides oritavancin and dalbavancin and the lipopeptide daptomycin. Topoisomerase inhibitors include the fluoroquinolones gemifloxacin, sitafloxacin and garenoxacin. Protein synthesis inhibitors are represented by the ketolides telithromycin and cethromycin, the oxazolidinones and the glycylcycline tigecycline. Although each of these compounds has demonstrated antibacterial activity against antibiotic-resistant pathogens, their final regulatory approval will depend on an acceptable clinical safety profile.     

Novel antibacterial agents for the treatment of serious Gram-positive infections

With the continuing development of clinical drug resistance among bacteria and the advent of resistance to the recently released agents quinupristin-dalfopristin and linezolid, the need for new, effective agents to treat multi-drug-resistant Gram-positive infections remains important. This review focuses on agents presently in clinical development for the treatment of serious multidrug-resistant staphylococcal, enterococcal and pneumococcal infections, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and penicillin-resistant Streptococcus pneumoniae. Agents to be discussed that affect the prokaryotic cell wall include the antimethicillin-resistant S. aureus cephalosporins BAL9141 and RWJ-54428, the glycopeptides oritavancin and dalbavancin and the lipopeptide daptomycin. Topoisomerase inhibitors include the fluoroquinolones gemifloxacin, sitafloxacin and garenoxacin. Protein synthesis inhibitors are represented by the ketolides telithromycin and cethromycin, the oxazolidinones and the glycylcycline tigecycline. Although each of these compounds has demonstrated antibacterial activity against antibiotic-resistant pathogens, their final regulatory approval will depend on an acceptable clinical safety profile.     

头孢硫脒在治疗革兰阳性菌烧伤感染中的作用

目的 探讨应用头孢硫脒在防治革兰阳性菌烧伤感染中的作用。方法 140例烧伤感染患者随机分成两组。试验组76例，应用头孢硫脒治疗；对照组64例，给予头孢呋辛治疗。疗程7-14d，并进行细菌敏感性试验。结果 头孢硫脒组有效率95％，头孢呋辛组有效率44％，两组总有效率有显著差异（P〈0．01）。烧伤感染革兰阳性菌的主要致病菌对头孢硫脒的敏感性较高。体外药敏试验显示头孢硫脒对细菌的清除率为87．17％。结论 临床研究证实头孢硫脒对治疗烧伤革兰阳性菌疗效良好。可作为治疗烧伤革兰阳性菌感染的一线应用抗生素。     

Synthesis and antibacterial activity of substituted oxotriazolylphenyl oxazolidinones

A series of 3-(4'-(2'-alkyl-3'-oxy-1',2',4'-triazolyl)-phenyl)-5-substituted oxazolidinones was designed and synthesized for in vitro antibacterial activity testing against fourteen Gram-negative and six Gram-positive standard organisms. The minimum inhibitory concentration (MIC) was determined by agar dilution at concentrations of 0.10, 0.20, 0.39, 0.78, 1.56, 3.13, 6.25 microg/mL. Different alkyl groups at the 2'-position played an important role in the activity against Gram-positive organisms. (S)-3-(4'-(2'-ethyl-3'-oxy-1',2',4'-triazolyl)-phenyl)-5-acetamidomethyloxazolidinone was active against Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus enteridis and Streptococcus nonhemolyticus, whereas 2'-methyl, 2'-propyl and 2'-n-butyl counterparts did not show activity at 6.25 microg/mL. Modification of the 5-substitutent of oxazolidinones also affected the activity against Gram-positive organisms. (S)-3-(4'-(2'-ethyl-3'-oxy-1',2',4'-triazolyl)-phenyl)-5-acetamidomethyloxazolidinones was approximately two fold more potent than 5-chloroacetamido, 5-dichloroacetamido and 5-trifluoroacetamido counterparts against Streptococcus enteridis. None of these compounds showed growth inhibition against fourteen Gram-negative organisms at 6.25 microg/mL.     

恶唑烷酮类抗菌药利奈唑胺的研究进展

利奈唑胺属于新型恶唑烷酮类抗菌药物 ,在体内外对引起社区和院内各种感染的阳性细菌具有广谱抗菌作用 ,包括耐青霉素肺炎链球菌 ,耐甲氧西林金黄色葡萄球菌和耐万古霉素肠球菌等 ,其临床疗效已经得到一系列Ⅲ期临床研究的证明。本文综述了第 1个应用于临床的恶唑脘酮类药物利奈唑胺的发展历史 ,抗菌作用 ,临床试验和安全性等方面的进展。     

16种抗菌药物对来源于免疫功能低下患者的革兰氏阴性杆菌的体外抗菌活性比较

对从武汉地区免疫功能低下患者分离的１０６３株革兰氏阴性杆菌，用琼脂平皿稀释法测定１６种抗菌药物的最小抑菌浓度（ＭＩＣ）。用ＷＨＯＮＥＴ－３计算机软件完成数据分析。主要革兰氏阴性杆菌是铜绿假单胞菌（３２．５％）、大肠杆菌（２２．９％）、克雷伯氏菌属（１４．３％）、肠杆菌属（７．９％）、不动杆菌属（６．１％）和柠檬酸菌属（４．９％）。通过ＭＩＣ测定显示大部分菌株对１６种抗菌药物有不同程度的耐药性。４７．２％的菌株同时对５种以上抗菌药物耐药。１０６３株革兰氏阴性杆菌对亚胺培南／西司他丁最敏感，其次是对阿米卡星和头孢他啶，敏感率分别为９５％、８８％和８６％。亚胺培南／西司他丁的体外抗菌活性最高，ＭＩＣ５０和ＭＩＣ９０为０．５和２μｇ／ｍｌ，阿米卡星（ＭＩＣ５０和ＭＩＣ９０为２和６４μｇ／ｍｌ）及头孢他啶（ＭＩＣ５０和ＭＩＣ９０为２和３２μｇ／ｍｌ）次之。根据对１６种药物抗菌活性的比较，为正确合理使用抗菌药物治疗免疫功能低下者革兰氏阴性杆菌急危重症感染提供了依据     

Synthesis and in vitro evaluation of substituted phenyl-piperazinyl-phenyl oxazolidinones against Gram-positive bacteria

With the incidence of linezolid-resistant Enterococcus faecalis, E. faecium and Staphylococcus aureus, modification of linezolid at the 5- and/or 3-positions led to the development of a series of 3-(methoxyl-phenyl)-piperazinyl-phenyl oxazolidinone analogues. These compounds were tested in vitro against six gram-positive standard organisms (S. aureus, S. epidermidis, S. pneumoniae, S. albus, Streptococcus enteridis and S. nonhemolyticus). 5-acetylaminomethyl oxazolidinones bearing fluorine at 3'-position of phenyl ring showed activities against several gram-positive bacteria (MIC: 3.13-6.25 mug/mL). The position of methoxyl group on the phenyl ring of piperazine group affected antibacterial spectrum. 3-(4'- (para-methoxyl-phenyl)-piperazinyl)-(3'-fluoro)-phenyl-5-acetylaminomethyl oxazolidinone was found active against 5 gram-positive organisms except S. nonhemolyticus, whereas 3-(4'-(ortho-methoxyl-phenyl)-piperazinyl)-(3'-fluoro)-phenyl-5-acetylaminomethyl oxazolidinone was found active only against 2 gram-positive organisms, namely S. albus, S. enteridis.     

噁唑烷酮类抗菌药物研究进展

抗生素的广泛使用使得细菌的耐药性问题日益严重,新型抗耐药菌药物的研究已成为抗菌药物研究的主要方向。其中,全合成的噁唑烷酮类抗菌药物利奈噁唑酮已成功上市,并取得了良好的临床治疗效果,这促使了对该类化合物更为深入的研究。本文对噁唑烷酮类抗菌剂的作用机制、耐药机制、结构修饰进行综述,并着重介绍了近年来具有优良抗菌活性的噁唑烷酮类潜在药物。     

Exploration of (3-benzyl-5-hydroxyphenyl)carbamates as new antibacterial agents against Gram-positive bacteria

A series of (3-benzyl-5-hydroxyphenyl)carbamates were evaluated as new antibacterial agents. Several compounds showed potent inhibitory activity against sensitive and drug-resistant Gram-positive bacteria. The compounds are ineffective against all tested Gram-negative bacteria. The structure of the ester group exerted a profound effect on antibacterial activity. 4,4-Dimethylcyclohexanyl carbamate 6h exhibited the most potent inhibitory activity against the standard and clinically isolated Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis (minimum inhibitory concentration = 4–8 µg/ml) strains. The preliminary experimental evidence indicated that these carbamates target the bacterial cell wall and share a similar mechanism of action with vancomycin.