铜绿假单胞菌体外抑菌活性研究

目的 观察铜绿假单胞菌抗菌物质对鲍曼不动杆菌等细菌的体外抑菌效果.方法 用交叉条带实验方法检测了铜绿假单胞菌对鲍曼不动杆菌、耐甲氧西林表皮葡萄球菌和粪肠球菌的体外抑制活性.结果 铜绿假单胞菌对鲍曼不动杆菌、耐甲氧西林表皮葡萄球菌和粪肠球菌体外抑菌活性良好,10株铜绿假单胞菌中,有8株对鲍曼不动杆菌的抑制率均达到了100％.另外有8株对耐甲氧西林表皮葡萄球菌的抑菌率均为100％;有6株对粪肠球菌的抑菌率为100％.结论 铜绿假单胞菌对上述3种致病菌具有较强的抗菌活性,具有开发前景.     

抗耐药细菌药用植物内生菌的筛选与鉴定

耐甲氧西林金黄色葡萄球菌(MRSA)、耐头孢霉素大肠杆菌和耐亚胺培南铜绿假单胞菌在医院临床治疗中引起的严重感染,极大地危害着人类身体健康。旨在从植物组织中分离和筛选高活性的拮抗上述耐药细菌的内生菌株。从分离自22种药用植物组织的197株内生菌中,经过两步筛选获得18株对MRSA有拮抗作用的菌株,未筛选到对耐头孢霉素大肠杆菌和耐亚胺培南铜绿假单胞菌有拮抗作用的菌株;经16SrRNA序列分析,其中8株为链霉菌属,6株为芽孢杆菌属,4株为假单胞菌属;对抑菌效果较强的5株菌进行发酵培养,检测发酵液对MRSA的抑菌效果,其中QN1和CF2的发酵液对MRSA有很好的抑制效果。     

下呼吸道感染耐环丙沙星铜绿假单胞菌的分布与耐药性

目的了解耐环丙沙星铜绿假单胞菌的流行情况,分析耐环丙沙星铜绿假单胞菌的耐药性,比较耐环丙沙星铜绿假单胞菌与环丙沙星敏感铜绿假单胞菌的耐药性差异。方法选择贵阳医学院第三附属医院2011年6月至2014年11月下呼吸道感染标本中分离出的231株耐环丙沙星铜绿假单胞菌与环丙沙星敏感铜绿假单胞菌,按照《全国临床检验操作规程》进行微生物病原菌鉴定。采用Kirby-Bauer琼脂扩散法进行药敏试验,结果使用SPSS 17.0软件进行统计分析。结果下呼吸道感染标本中共分离出铜绿假单胞菌231株,其中耐环丙沙星铜绿假单胞菌检出率25.54%。从科室分布看,神经外科分离率最高,占47.46%,其次ICU、呼吸内科与消化内科分别占18.64%、13.56%、10.17%;下呼吸道感染耐环丙沙星铜绿假单胞菌菌株与环丙沙星敏感铜绿假单胞菌菌株对头孢曲松、阿米卡星、亚胺培南、哌拉西林/他唑巴坦、头孢哌酮/舒巴坦等19种抗菌药物的耐药率分别为95.65%,71.83%;42.86%,7.69%;17.39%,2.70%;33.33%,11.02%;22.22%,8.00%。下呼吸道感染耐环丙沙星铜绿假单胞菌菌株耐药率明显高于环丙沙星敏感铜绿假单胞菌菌株,差异具有统计学意义(P0.05)。结论耐环丙沙星铜绿假单胞菌表现为多重耐药性,给临床治疗带来很大的困难。因此严格掌握抗菌药物的选用是延缓病原菌对抗菌药物耐药的有效方法。     

氯氰碘柳胺与环丙沙星对耐甲氧西林金黄色葡萄球菌的体外联合药敏试验分析

目的 评价氯氰碘柳胺与环丙沙星联用对60株环丙沙星均为耐药的耐甲氧西林金黄色葡萄球菌(MRSA)的体外抗菌效应.方法 采用棋盘法设计,微量肉汤稀释法测定不同浓度组合的抗菌药物对60株甲氧西林耐药的金黄色葡萄球菌(MRSA)的最低抑菌浓度,并计算部分抑菌浓度指数(FICI)判定联合效应.结果 氯氰碘柳胺与环丙沙星联合用药后,其FICI分布:FIC≤0.5为20.0％,0.5 ＜FIC≤1为66.7％,1＜FIC≤2为13.3％,FIC＞2为0.结论 体外氯氰碘柳胺与环丙沙星联用对60株耐甲氧西林金黄色葡萄球菌的作用主要为相加和协同作用.     

抗菌肽Lfcin15-Me8分子设计及对老年呼吸道致病菌铜绿假单胞菌的抑菌性能分析

探讨人工设计合成的Lfcin15-Me8分子对老年病患者中铜绿假单胞菌抑菌活性研究。从老年病患痰液中分离鉴定铜绿假单胞菌(Pseudomonas aeruginosa)感染情况,截取牛乳铁蛋白素(Lfcin B)1-15和蜂毒素(Melittin)1-8核心氨基酸序列,固相合成新型抗菌肽分子,采用微量肉汤稀释法,测定新型抗菌肽分子对临床分离菌株的抑菌活性。结果显示,铜绿假单胞菌占院内感染的32.2%,位列致病菌第二位。合成的新型抗菌肽分子Lfcin15-Me8,为阳离子型抗菌肽,并富含α-螺旋。对临床铜绿假单胞菌抑菌MIC值均达到128μg/m L以下,其中最低达到32μg/m L,具有良好抗菌活性。铜绿假单胞菌在老年呼吸道感染中占较大比重,需注意防控,人工合成的Lfcin15-Me8分子可抑制临床铜绿假单胞菌的生长繁殖。     

126株铜绿假单胞菌的临床分布及耐药性分析

目的调查分析象山县中医医院铜绿假单胞菌的临床分布及药敏情况,为临床合理选用抗生素提供可靠的依据。方法采集疑似患者的标本,进行分离、培养与鉴定。采用自动微生物鉴定／药敏分析仪进行鉴定及药敏试验,对2012年7月至2013年10月分离出的126株铜绿假单胞菌（包括21株黏液型铜绿假单胞菌）的分布及耐药性进行回顾性分析。结果126株铜绿假单胞菌临床主要分布情况：痰占80．2％,尿液占11．1％,脓液占7．1％,以呼吸道感染为主。对铜绿假单胞菌保持活性较强同时耐药率〈20％的抗生素有阿米卡星、妥布霉素、亚胺培南、哌拉西林／他唑巴坦,其中碳青霉烯类耐药率升至5％,原来被认为抗铜绿假单胞菌较为有效的喹诺酮类抗生素的耐药率也有了很大提升,左氧氟沙星耐药率升至33％。黏液型铜绿假单胞菌的体外抗菌药物敏感试验耐药性较弱,且明显弱于非黏液型铜绿假单胞菌的耐药性。结论铜绿假单胞菌为医院呼吸道感染的常见致病菌,对多种抗菌药物呈不同程度耐药。加强动态监测,合理使用抗菌药物,对铜绿假单胞菌感染的预防和药物治疗具有重要指导意义。     

2004～2010年武汉同济医院临床分离多重耐药菌株监测分析

目的了解武汉同济医院2004年至2010年临床分离多重耐药菌株的检出情况。方法对临床分离菌株,采用纸片扩散法按统一的方案进行药敏试验。按照CLSI 2009年标准进行判断。结果 2004年至2010年该院耐甲氧西林金葡菌（MRSA）和耐甲氧西林凝固酶阴性葡萄球菌（MRSCN）的检出率分别在35.6%～63.8%和21.5%～61.4%。2004年至2010年共检出36株耐万古霉素肠球菌（VRE）。大肠埃希菌产ESBLs株检出率在29.6%～81.7%,肺炎克雷伯菌产ESBLs株检出率在36.0%～56.6%,产酸克雷伯产ESBLs株检出率在35.3%～67.4%,奇异变形杆菌产ESBLs株检出率在0～26.2%。自2005年起每年均有泛耐药的铜绿假单胞菌和鲍曼不动杆菌的检出。结论该院2004年至2010年多重耐药菌株呈增多趋势,尤其是VRE和泛耐药的铜绿假单胞菌和鲍曼不动杆菌的出现,给临床治疗带来了严峻挑战。     

10种中草药提取物体外抗铜绿假单胞菌作用研究

通过对粗糠柴等10种中草药采用80%乙醇室温下浸渍制备的提取物进行体外抗铜绿假单胞菌及其耐药菌活性研究,并采取药敏纸片法测定临床分离菌株的耐药性。结果表明:这10种中草药80%乙醇提取物中,粗糠柴的乙酸乙酯层对铜绿假单胞菌标准菌及其耐药菌的抑菌效果最好,其抑菌圈直径范围在10~17 mm之间,MIC范围在0.125~0.5 mg·mL~(-1)之间,MBC范围在0.5~1 mg·mL~(-1)之间;正丁醇层、水层的抑菌活性较乙酸乙酯层弱,石油醚层对铜绿假单胞菌没有效果。而小叶藤黄、滇南红厚壳、续随子的乙酸乙酯层,巴豆、罗汉松、肉桂醇提物对铜绿假单胞菌及其耐药菌株有较弱抗菌活性;滇南红厚壳的正丁醇层、续随子乙酸乙酯层以及大八角和郁金的醇提物对铜绿假单胞菌及其耐药菌株均无活性。从这些数据中可以得出,粗糠柴的乙酸乙酯层、正丁醇层和水层对铜绿假单胞菌及其耐药菌有较好的抑菌活性,尤以乙酸乙酯层活性最好,而粗糠柴的石油醚层没有活性。     

2013年新疆17家三级医院细菌耐药性监测分析

目的:了解新疆地区17家三级医院2013年临床分离细菌的分布特征及对抗生素的耐药性。方法:采用最小抑菌浓度法(MIC)和纸片扩散法(K-B)对细菌进行药物敏感试验。结果:临床共分离出细菌44022株,其中革兰阳性菌占30.2%,革兰阴性菌占69.8%。1大肠埃希菌、肺炎克雷伯菌和奇异变形杆菌产ESBLs菌株检出率分别为66.2%、48.0%和52.0%。2鲍曼不动杆菌和铜绿假单胞菌对亚胺培南和美洛培南的耐药率分别为51.8%、30.4%和37.6%、22.9%。3耐甲氧西林金黄色葡萄球菌(MRSA)和耐甲氧西林凝固酶阴性葡萄球菌(MRSCN)的检出率分别为27.7%和79.8%。414岁以下儿童肺炎链球菌对青霉素的耐药率(4.2%)高于成人(2.1%)。泛耐药菌株(XDR)中,鲍曼不动杆菌381株(9.6%),铜绿假单胞菌57株(1.7%),大肠埃希菌6株(0.1%),肺炎克雷伯菌16株(0.3%)。结论:通过对细菌耐药数据分析情况来看,细菌耐药情况普遍存在,对于耐药克隆株的传播,应加以关注;此外,应加强细菌耐药监测,合理使用抗生素。     

原始热带雨林鹦歌岭土壤抗MRSA放线菌的分离与筛选

鹦歌岭是位于海南省乐东县的原始热带雨林,从鹦歌岭土壤中分离与筛选抗耐甲氧西林金黄色葡萄球菌(MRSA)的放线菌。采用平板稀释法分离,以MRSA作为受试菌株,测试抗菌活性,对具有抗菌活性的菌株进行16S rDNA序列测定。采用滤纸片法,测定菌株发酵粗提液对MRSA抑菌活性,并用高效液相色谱仪检测粗提液的活性物质。从鹦歌岭土壤中共分离到168株放线菌,其中10株具有较强的抗MRSA活性,发酵液粗提物抑菌圈直径在8 mm-25 mm之间;16S rDNA序列比对发现,10株菌均与链霉菌属(Streptomyces)的相似性达99%以上,初步确定是链霉菌属的放线菌。通过对比10株菌发酵液HPLC指纹图谱,发现菌株7、5和9-1的发酵液次级代谢产物丰富,活性测试表明,10株放线菌对MRSA的生长均有明显的抑制作用。     

Synthesis and antibacterial activity of 5-deoxy-5-episubstituted arbekacin derivatives

5-Deoxy-5-episubstituted arbekacin derivatives have been designed and efficiently synthesized. The synthetic compounds showed potent antibacterial activity against both Staphylococcus aureus, including methicillin-resistant S. aureus, and Pseudomonas aeruginosa. In particular, these derivatives were superior to arbekacin against MRSA strains expressing the bifunctional aminoglycoside-modifying enzyme AAC(6')-APH(2'). The antibacterial activity of the 5-deoxy-5-episubstituted arbekacin derivatives against Pseudomonas aeruginosa was markedly influenced by the efflux system of MexXY/OprM. The 6'-N-methyl derivative of the 5-epi arbekacin was effective against Pseudomonas aeruginosa expressing the aminoglycoside-modifying enzyme AAC(6').     

Structure--activity relationships of 1beta-methyl-2-(5-phenylpyrrolidin-3-ylthio)carbapenems

Structure--activity relationship studies of 1beta-methyl-2-[(3S,5R)-5-(4-aminomethylphenyl)pyrrolidin-3-ylthio]carbapenems, especially those pertaining to the relationship between antibacterial activity and side-chain structure were conducted. These studies suggested that the trans-(3S,5R)-5-phenylpyrrolidin-3-ylthio side-chain and the aminomethyl group at the 4-position of the phenyl ring play a key role in enhancing the antibacterial activity against the MRSA and Pseudomonas aeruginosa strains. In particular, the basicity of a substituent at the 4-position of the phenyl ring were shown to greatly contribute to the antibacterial activity against MRSA and methicillin-resistant Staphyloccocus epidermidis strains. In contrast, the amidine group was shown to lead to potent antibacterial activity against P. aeruginosa strains comparable to that of imipenem, however, a good correlation between the basicity of the 4-substituent and antipseudomonal activity was not observed. In conclusion, the 4-aminomethyl or methylaminomethyl group on the phenyl ring was the best substituent for antipseudomonal activity.     

Drug susceptibility of Pseudomonas aeruginosa strains isolated from patients of a hospital and specialistic outpatients clinics of the SP ZOZ in Nidzica

The aim of this study was to evaluate a frequency of isolation and antimicrobial susceptibility testing (AST) of Pseudomonas aeruginosa strains cultured from clinical specimens collected from patients hospitalized in wards and specialistic outpatients clinics of a hospital in Nidzica (01. 09. 2000 -31. 12. 2003). During over three years 392 Pseudomonas aeruginosa strains were cultured from 16346 clinical samples provided to bacteriological laboratory. P. aeruginosa strains were isolated from 2.5% of examined specimens. Susceptibility of Pseudomonas aeruginosa strains to antimicrobial agents was tested. The highest in vitro activity against clinical P. aeruginosa strains demonstrated imipenem. One strain was resistant to imipenem. This strain was isolated from a patient of a surgical department. Metalo-beta-lactamase was not detected (MBL-negative strain).Twenty nine strains were ESBL producer (7.4% of all strains). The contribution of Pseudomonas aeruginosa strains to the etiology of nosoconial and ambulatory infections increases. In vitro activity of antibacterial agents against P. aeruginosa strains should be monitored during therapy of infections. Resistance to antibiotics/chemothe-rapeutics may be acquired during treatment with antibacterial agent to which P. aeruginosa strain was susceptible according to the antibiogram.     

Antioxidant, radical-scavenging, anti-inflammatory, cytotoxic and antibacterial activities of methanolic extracts of some Hedyotis species

The antioxidant, radical-scavenging, anti-inflammatory, cytotoxic and antibacterial activities of methanolic extracts of seven Hedyotisspecies were investigated. The antioxidant activity was evaluated by the ferric thiocyanate (FTC) and thiobarbituric acid (TBA) methods while the radical scavenging activity was measured by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. The anti-inflammatory activity related to NO inhibition of the plant extracts was measured by the Griess assay while cytotoxicity were measured by the MTT assay against CEM-SS cell line. The antibacterial bioassay (against 4 bacteria, i.e. Bacillus subtilis B28 (mutant), Bacillus subtilis B29 (wild-type), Pseudomonas aeruginosa UI 60690 and methicillin resistant Staphylococcus aureus, (MRSA) was also carried out using the disc-diffusion method. All tested extracts exhibited very strong antioxidant properties when compared to Vitamin E (alpha-tocopherol) with percent inhibition of 89-98% in the FTC and 60-95% in the TBA assays. In the DPPH method, H. herbacea exhibited the strongest radical scavenging activity with an IC50 value of 32 microg/ml. The results from the Griess assay showed that the tested extracts are weak inhibitors of NO synthase. However, all tested extracts exhibited moderate cytotoxic properties against CEM-SS cell line giving CD50 values in the range of 21-41 microg/ml. In the antibacterial bioassay, the stems and the roots of H. capitellata showed moderate activity against the 4 tested bacteria while the leaves showed moderate activity towards B. subtilis B28, MRSA and P. aeruginosa only. The roots of H. dichotoma showed strong antibacterial activity against all 4 bacteria. All other extracts did not exhibit any antibacterial activity.     

Antibacterial activity of crude methanolic extract and its fractions of aerial parts of Anthemis tinctoria

The antibacterial activity of the methanolic extract and its fractions of aerial parts of Aniheinis tinctoria (Asteraceae) was investigated against representative gram-positive Staphylococcus aureus (ATCC 25923) and Enterococcus faecalis (ATCC 29212) and gram-negative strains Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853). The activity was concentrated mainly in the dichloromethane (DCM) and hexane fractions of crude methanolic extract. The 5 mg of DCM extract per disk produced 15-16 mm of inhibition zone against S. aureus and P. aeruginosa, however, no activity was found against E. faecalis and E. coli. The hexane fraction showed activity against S. aureus, P. aeruginosa and E. faecalis. As DCM fraction showed the highest antibacterial activity in the disk diffusion assay, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of only this fraction was determined against S. aureus and P. aeruginosa. These values were found to be in the range of 1.25 to 10 mg/ml.     

CP0569, a new broad-spectrum injectable carbapenem. Part 1: synthesis and structure-activity relationships

A series of 1beta-methylcarbapenems bearing an (imidazo[5,1-b]thiazolium-6-yl)methyl moiety, a 5,5-fused heterobicycle, at the C-2 position was synthesized and evaluated for in vitro antibacterial activities. CP0569 (1r) and its analogues showed potent antibacterial activities against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and Gram-negative bacteria, including Pseudomonas aeruginosa. Moreover, CP0569 (1r) exhibited stronger antibacterial activity against MRSA and higher resistance to renal dehydropeptidase-1 (DHP-1) than any currently marketed carbapenems, that is, imipenem (IPM), panipenem (PAPM), and meropenem (MEPM).     

Antibacterial activity of coumarins

The antibacterial activity of coumarin per se and other 45 coumarin derivatives was tested against strains of Bacillus cereus MIP 96016, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, and Staphylococcus aureus ATCC 25923. The inhibitory effects of coumarins were affected by their substitution patterns. Osthenol (44) showed the most effective antibacterial activity against Gram-positive bacteria with MIC values ranging between 125 and 62.5 microg/ml. These results suggested that the prenyl chain of 44 at position 8 and the presence of OH at position 7 of the benzenic ring are required for the antibacterial activity against these strains.     

Effect of varying the 4'-position of arbekacin derivatives on antibacterial activity against MRSA and Pseudomonas aeruginosa

4'-Deoxy-4'-episubstituted arbekacin derivatives and 4'-epi-5-deoxy-5-episubstituted arbekacin derivatives were designed and synthesized. Arbekacin and 4'-epiarbekacin both displayed the same antibacterial activity against Staphylococcus aureus (including methicillin-resistant S. aureus (MRSA)) and Pseudomonas aeruginosa. The 4'-epi-5-deoxy-5-episubstituted arbekacin derivatives showed potent antibacterial activity. Among them, the antibacterial activity of 5,4'-diepiarbekacin was superior to that of arbekacin or 5-episubstituted arbekacin against Gram-positive and Gram-negative bacteria. The 6'-N-methyl derivative of the 5,4'-diepiarbekacin was effective against P. aeruginosa expressing an aminoglycoside-modifying enzyme AAC(6')-Ib.     

Antibacterial activity, structure and CMC relationships of alkanediyl alpha,omega-bis(dimethylammonium bromide) surfactants

Some alpha,omega-alkanediyl bis-dimethylammonium bromide compounds (gemini surfactants) referred as "m-s-m" have been synthesized, purified and characterized by usual spectroscopic methods. These compounds have been screened for antibacterial activity against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Their activity was compared. The compounds tested showed excellent in vitro antibacterial activity against Staphylococcus aureus ranging from 1.5 to 20 microg/ml and had variable activity against E. coli with minimum minimum inhibitory concentration (MIC) of 50 microg/ml. These compounds are less active against P. aeruginosa. On the other hand, contrary to the antibacterial activity of these products against S. aureus, a relation between the MIC and the critical micellar concentration (CMC) was found and relationship between chain's Length and antibacterial activity was found.