利奈唑胺与万古霉素对耐甲氧西林金黄色葡萄球菌体外抗菌活性

目的 评价利奈唑胺(嗯唑烷酮类抗菌药)、万古霉素(胺基糖苷类抗生素)2种抗菌药物对耐甲氧西林金黄色葡萄球菌(MRSA)的体外抗菌活性.方法 用琼脂二倍稀释法,测定抗菌药物的最低抑菌浓度(MIC);用肉汤稀释法,测定抗菌药物的最低杀菌浓度(MBC),绘制杀菌曲线(KCs).结果 利奈唑胺对临床分离的98株MRSA的MIC50为1 μg·mL-1,MIC90为2 μg·mL-1,MBC50为8 μg·mL-1,MBC90为32 μg·mL-1,敏感率为100%;万古霉素对临床分离的98株MRSA的MIC50为1 μg·mL-1,MIC90为1 μg·mL-1,MBC50为8 μg·mL-1,MBC90为32 μg·mL-1,敏感率为100%.随着抗菌药物浓度的升高,其杀菌时间缩短不甚明显,呈现非浓度依赖性的特点.结论 利奈唑胺对MRSA的体外抗菌活性与万古霉素相当,均显示非浓度依赖性的杀菌曲线.     

Sansanmycin A对铜绿假单胞菌体内外抗菌活性的初步研究

目的评价sansanmycin A对临床分离铜绿假单胞菌的体内、外抗菌活性。方法体外试验以微量肉汤稀释法测定sansanmycin A同时对照10种药物对150株铜绿假单胞菌的最低抑菌浓度(MIC),以平皿计数法测定最低杀菌浓度(MBC);半体内试验以微量稀释法测定sansanmycin A的血清抑菌活性(SBS)和血清杀菌活性(SBA)。结果 Sansanmycin A对铜绿假单胞菌体外抗菌活性与哌拉西林相似,其MIC50和MBC50分别为8和16μg/mL,MIC范围为2~>512μg/mL,MBC范围为2~>512μg/mL,头孢曲松和替卡西林对铜绿假单胞菌的MIC50和MBC50较sansanmycin A高2~4倍。Sansanmycin A对铜绿假单胞菌显示浓度依赖性杀菌作用。Sansanmycin A对铜绿假单胞菌峰时SBS和SBA中位数分别为1:256和1:128。结论 Sansanmycin A对铜绿假单胞菌显示较强的体外和体内杀菌活性,有进一步研究和开发的价值。     

清肺消炎丸体外抗菌活性研究

目的观察清肺消炎丸对9种肺炎常见病原菌的体外抗菌作用。方法采用琼脂稀释法,测定清肺消炎丸对9种药敏质控菌株的最低抑菌浓度(MIC)及最低杀菌浓度(MBC)。结果清肺消炎丸对肺炎链球菌、化脓性链球菌、金黄色葡萄球菌、流感嗜血杆菌的MIC分别为6.25、25、25、50mg/mL,相应的MBC分别为12.5、25、50、50mg/mL;对大肠杆菌、铜绿假单胞菌、肺炎克雷伯菌、变形杆菌及白色念珠菌均无明显体外抑菌活性。结论清肺消炎丸对肺炎链球菌、化脓性链球菌、金黄色葡萄球菌、流感嗜血杆菌具有体外抗菌作用,其中对链球菌的抗菌活性较高。     

黄芩素对耐甲氧西林金黄色葡萄球菌的体外抗菌活性研究

目的:了解黄芩素对耐甲氧西林金黄色葡萄球菌(MRSA)的体外抗菌活性。方法:用美国临床实验室标准化委员会(CLSI/NCCLS)介绍的方法,检测黄芩素和万古霉素对117株临床分离的MRSA的体外抗菌活性。结果:黄芩素对MRSA的MIC_(50)、MIC_(90)和MBC分别为32.0、96.0和168.0μg/mL。结论:黄芩素为一种对MRSA敏感的抗菌药物,可用于临床治疗由MRSA感染引起的多种疾病。     

广西藤茶提取物APS体外抗菌作用研究

目的: 观察从广西藤茶中提取得到的一个单体化合物(简称APS) 的体外抗菌作用。方法: 利用琼脂稀释法对标准金黄色葡萄球菌(S. aureus) 、耐甲氧西林金黄色葡萄球菌( MRSA) 、绿脓杆菌( P.aeruginosa) 、大肠杆菌(E.coli) 、乙型溶血性链球菌( β-hemolytic streptococcus) 、福氏痢疾杆菌( Shigella flexneri) 、白色葡萄球菌(Staphylococcus albus)、奈氏菌(Neisseria)、白色念珠菌(Candida albicans)、枯草杆菌(Bacillus subtilis)进行最低抑菌浓度( MIC) 测定, 并与盐酸黄连素相比较, 利用不同浓度 APS 对标准金黄色葡萄球菌、MRSA、绿脓杆菌进行体外杀菌曲线测定。结果: 对 S. aureus、MRSA、P. aeruginosa、E.coli、β- hemolytic strepto-coccus、Shigella lexneri、Staphylococcus albus、Neisseria、Candida albicans、Bacillus subtilis 的 MIC 值分别为 0.078、0.078、1.25、0.31、2.5、1.25、0.625、2.5、5、1.25mg/mL; 体外杀菌曲线表明, APS 对 S. aureus、MRSA、P. aeruginosa 有直接抑制作用, 且与药物剂量呈正相关。结论: APS 体外具有明显的抗菌作用。     

含氨基噻唑肟结构的膦酸酯衍生物的合成与抗菌活性研究

采用分子杂合原理,将氨基噻唑肟与膦酸酯片段组合,设计合成了15个目标物进行抗菌活性研究。结果显示:该类衍生物对所测试细菌有较好的抑制作用,尤以化合物Ⅲf和Ⅲi的抗金葡菌(S.aureus)、大肠杆菌(E.coli)、耐甲氧西林金葡菌(MRSA)和耐氟喹诺酮大肠杆菌(FREC)活性最为显著,前者的最小抑菌浓度(MIC)分别为1、8、4和16μg·mL^-1,后者的MIC分别为4、4、16和8μg·mL^-1,抗S.aureus活性略低于苯唑西林,抗E.coli、MRSA和FREC活性优于对照药苯唑西林,值得进一步深入研究。     

头孢曲松-川参通注射液配伍液抗菌活性的观察

目的观察川参通注射液与头孢曲松配伍的抗菌活性及稳定性.方法将川参通注射液与头孢曲松钠注射液混合,以分光光度仪检测其吸光度值并以最低抑菌浓度(MIC)和最低杀菌浓度(MBC)试验检测其对粪链球菌、淋病奈瑟菌、大肠埃希菌及普通变形杆菌的抑菌与杀菌活性.结果头孢曲松-川参通配伍液外观为棕色澄清液体,无沉淀、浑浊或絮状物形成,405nm波长处的吸光度值小于川参通注射液的吸光度值.头孢曲松-川参通注射液配伍液对粪链球菌的MIC为200μg/mL/0.8μL/mL,MBC为500μg/mL/2μL/mL;对淋病奈瑟菌的MIC为0.1μg/mL/0.0004μL/mL,MBC为0.1μg/mL/0.0004μL/mL;对大肠埃希菌的MIC为0.005μg/mL/0.00002μL/mL,MBC为0.5μg/mL/0.002μL/mL;对变形杆菌的MIC为0.01μg/mL/}μL/mL,MBC为0.01μg/mL/0.00004μL/mL,较配伍前降低或不变.结论川参通注射液与头孢曲松配伍后未见浑浊或沉淀,对淋病奈瑟菌与大肠埃希菌的抗菌活性增高,对粪链球菌与普通变形杆菌的抗菌活性不变.     

复方奥硝唑栓剂的体外抗菌活性研究

目的:测定复方奥硝唑栓剂的体外抗菌活性。方法:采用液体连续稀释法测定复方奥硝唑栓剂对金黄色葡萄球菌、大肠杆菌、粪肠球菌及脆弱拟杆菌的最小抑菌浓度(MIC)和最小杀菌浓度(MBC),以氧氟沙星栓剂和替硝唑栓剂作为对照。结果:复方奥硝唑栓剂对大肠杆菌、金黄色葡萄球菌、粪肠球菌及脆弱拟杆菌均显示很强的抗菌活性,其MIC值分别为0.061,0.015,0.490,0.031μg/mL;MBC值分别为0.120,0.031,0.980,0.031μg/mL。无论是标准菌株还是临床分离的菌株,其MIC及MBC均明显低于氧氟沙星及替硝唑栓剂。结论:复方奥硝唑栓剂对治疗妇科炎症具有明显的临床意义,值得临床推广应用。     

稠环磺酰胺衍生物的合成与抗菌活性研究

为了寻找抗菌候选化合物,在前期研究基础上,18个稠环磺酰胺衍生物被设计合成,经1H NMR、13C NMR和MS确认结构。采用两倍稀释法对目标物进行体外抗菌活性测试,结果表明:该类衍生物对所测细菌有不同程度的抑制活性,尤以化合物Ⅱi、Ⅱr的抗菌活性最为突出,其中前者对金葡菌(S.aureus)、大肠埃希菌(E.coli)和耐甲氧西林金葡菌(MRSA)的最小抑菌浓度(MIC)分别为8、32和16μg·mL^-1,后者对S.aureus、E.coli及MRSA的MIC分别为8、64和32μg·mL^-1,两者的抗MRSA活性较显著,值得进一步结构优化和深入研究。     

7-[3-氨甲基-4-(脲亚氨基)吡咯烷-1-基]喹诺酮衍生物的合成与抗菌作用研究

目的 寻找新的喹诺酮类抗菌药.方法 设计合成7-位具有较强亲水性取代基的7个氟喹诺酮衍生物,测定其体外抗菌活性.结果 化合物10对金葡菌(包括MRSA)和表葡菌(包括MRSE)的活性(MIC:0.06～4μg/mL)与左氧氟沙星和吉米沙星基本相当.化合物11对肺炎链球菌08-2的活性(MIC:0.25μg/mL)分别是左氧氟沙星和吉米沙星的128倍和32倍,化合物12对肺炎克雷伯菌09-22和09-23的活性(MIC:1μg/mL)分别是左氧氟沙星和吉米沙星的16倍和4倍,但目标物对革兰阴性菌的活性普遍弱于对照药.结论 7-位取代基的水溶性并非决定喹诺酮抗菌活性的主要因素.     

Antibacterial activity of gatifloxacin against various fresh clinical isolates in 2002

Antibacterial activities of gatifloxacin (GFLX) and other antibacterial drugs against various fresh clinical strains (800 isolates) isolated from specimens of patients in 2002 were compared. GFLX was more active than levofloxacin and ciprofloxacin against Gram-positive bacteria such as methicillin susceptible Staphylococcus aureus and Streptococcus pneumoniae. For these isolates, clarithromycin and azithromycin were less active (MIC90; > 16- > 64 micrograms/mL), GFLX was more active than cefdinir. For Escherichia coli, Klebsiella pneumoniae, Acinetobacter species, Haemophilus influenzae and Moraxella (Branhamella) catarrhalis, three quinolones including GFLX were potently active (MIC90; < or = 0.06-0.5 microgram/mL). Pseudomonas aeruginosa isolated from urinary tract infections were resistant to three quinolones including GFLX (MIC90; 32-64 micrograms/mL), however P. aeruginosa isolated from respiratory and otolaryngological infections were more susceptible (MIC90; 0.5-2 micrograms/mL). Quinolones were less active against Neisseria gonorrhoeae as compared with the cephem antibiotics tested, but GFLX was the most active against N. gonorrhoeae among the quinolones tested. In this study, we investigated activity of GFLX against fresh clinical strains isolated early in 2002, GFLX is widely and potently active against S. aureus, S. pneumoniae and various Gram-negative bacteria.     

司帕沙星和妥舒沙星的体内外抗菌作用研究

目的观察国产司帕沙星、妥舒沙星及其它四种氟喹诺酮类抗菌药对成都地区780株临床分离菌的体外抗菌活性，并比较司帕沙星、妥舒沙星和环丙沙星对金葡球菌、大肠埃希菌和铜绿假单胞菌感染小鼠的体内抗菌活性。方法用琼脂稀释法测定国产司帕沙星和妥舒沙星的MIC50和MIC90，并与其它四种氟喹诺酮类抗菌药进行了比较。本文还测定了抗菌药对金葡球菌、大肠埃希菌和铜绿假单胞菌感染小鼠治疗的ED50结果体外试验表明司帕沙星和妥舒沙星能有效抑制或杀灭革兰阳性、革兰阴性菌及厌氧菌，显示了广谱抗菌活性。司帕沙星和妥舒沙星对革兰阳性菌的抗菌活性是环丙沙星的2～8倍，氧氟沙星和氟罗沙星的4～16倍，是诺氟沙星的16～32倍。司帕沙星对MRSA的抗菌活性与妥舒沙星相似，但优于环丙沙星、氧氟沙星、氟罗沙星和诺氟沙星。司帕沙星对大多数革兰阴性菌的抗菌活性与环丙沙星和妥舒沙星相似，是氧氟沙星、氟罗沙星和诺氟沙星的2～8倍。两药对厌氧菌的抗菌活性也较环丙沙星强。口服或皮下注射司帕沙星对金葡球菌和大肠埃希菌所致小鼠全身性感染的保护作用优于环丙沙星和妥舒沙星。同一给药途径下司帕沙星对铜绿假单胞菌所致小鼠全身性感染的保护作用与妥舒沙星和环丙沙星相似。三种受试药对金葡球菌和大肠埃希菌所致小鼠全身性感染的保护作用优于铜绿假单胞菌所致感染。结论司帕沙星和妥舒沙星对革兰阳性菌和厌氧菌的体外抗菌活性优于环丙沙星和其它药物，对大多数革兰阴性菌的抗菌活性与环丙沙星相似，但优于其它受试药。司帕沙星对金葡球菌和大肠埃希菌所致小鼠全身性感染的体内保护作用优于环丙沙星和妥舒沙星。同一给药途径下司帕沙星对铜绿假单胞菌所致小鼠全身性感染的保护作用与妥舒沙星和环丙沙星相似。     

龙血竭对分离自伤口感染的铜绿假单胞菌的抗菌活性研究#br#

目的 探究龙血竭对分离自伤口感染的铜绿假单胞菌的抗菌活性,为临床合理使用龙血竭抗感染治疗提供依据。方法 收集2017年温州医科大学附属第一医院分离自伤口标本的铜绿假单胞菌26株,琼脂稀释法检测龙血竭对铜绿假单胞菌的最低抑菌浓度(MIC);生长曲线试验、半定量结晶紫染色法和细菌泳动试验分别检测龙血竭对铜绿假单胞菌的生长、生物膜形成能力、泳动能力的影响;实时荧光定量PCR方法检测生物膜形成相关基因的表达情况。结果 龙血竭对铜绿假单胞菌的MIC值为>5000μg/mL;512μg/mL龙血竭能降低铜绿假单胞菌的生长速率和最大生长量;各浓度的龙血竭能降低铜绿假单胞菌的生物膜形成能力;经龙血竭处理的铜绿假单胞菌的生物膜形成相关基因pslA、pelA、algD、algU的表达量有所降低;铜绿假单胞菌在含≥128μg/mL龙血竭的泳动平板表面的扩散直径减小。结论 龙血竭对铜绿假单胞菌的生长具有一定的抑制作用,并能通过降低pslA、pelA、algD、algU基因的表达水平降低其生物膜形成能力,同时可以降低细菌的泳动能力,进而在治疗铜绿假单胞菌所致的伤口感染中发挥作用。     

龙血竭对分离自伤口感染的铜绿假单胞菌的抗菌活性研究#br#

目的 探究龙血竭对分离自伤口感染的铜绿假单胞菌的抗菌活性,为临床合理使用龙血竭抗感染治疗提供依据。方法 收集2017年温州医科大学附属第一医院分离自伤口标本的铜绿假单胞菌26株,琼脂稀释法检测龙血竭对铜绿假单胞菌的最低抑菌浓度(MIC);生长曲线试验、半定量结晶紫染色法和细菌泳动试验分别检测龙血竭对铜绿假单胞菌的生长、生物膜形成能力、泳动能力的影响;实时荧光定量PCR方法检测生物膜形成相关基因的表达情况。结果 龙血竭对铜绿假单胞菌的MIC值为>5000μg/mL;512μg/mL龙血竭能降低铜绿假单胞菌的生长速率和最大生长量;各浓度的龙血竭能降低铜绿假单胞菌的生物膜形成能力;经龙血竭处理的铜绿假单胞菌的生物膜形成相关基因pslA、pelA、algD、algU的表达量有所降低;铜绿假单胞菌在含≥128μg/mL龙血竭的泳动平板表面的扩散直径减小。结论 龙血竭对铜绿假单胞菌的生长具有一定的抑制作用,并能通过降低pslA、pelA、algD、algU基因的表达水平降低其生物膜形成能力,同时可以降低细菌的泳动能力,进而在治疗铜绿假单胞菌所致的伤口感染中发挥作用。     

The depsidones from marine sponge-derived fungus Aspergillus unguis IB151 as an anti-MRSA agent: Molecular docking,pharmacokinetics analysis,and molecular dynamic simulation studies

Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging nosocomial pathogen among hospitalized patients, with high morbidity and mortality rates. The discovery of a novel antibacterial is urgently needed to address this resistance problem. The present study aims to explore the antibacterial potential of three depsidone compounds: 2-clorounguinol (1), unguinol (2), and nidulin (3), isolated from the marine sponge-derived fungus Aspergillus unguis IB1, both in vitro and in silico. The antibacterial activity of all compounds was evaluated by calculating the Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) against MRSA using agar diffusion and total plate count methods, respectively. Bacterial cell morphology changes were  studied for the first time using scanning electron microscopy (SEM). Molecular docking, pharmacokinetics analysis, and molecular dynamics simulation were performed to determine possible protein–ligand interactions and the stability of the targeting penicillin-binding protein 2a (PBP2a) against 2-clorounguinol (1). The research findings indicated that compounds 1 to 3 exhibited MIC and MBC values of 2 µg/mL and 16 µg/mL against MRSA, respectively. MRSA cells displayed a distinct shape after the addition of the depsidone compound, as observed in SEM. According to the in silico study, 2-chlorounguinol exhibited the highest binding-free energy (BFE) with PBP2a (-6.7 kcal/mol). For comparison, (E)-3-(2-(4-cyanostyryl)-4-oxoquinazolin-3(4H)-yl) benzoic acid inhibits PBP2a with a BFE less than −6.6 kcal/mol. Based on the Lipinski's rule of 5, depsidone compounds constitute a class of compounds with good pharmacokinetic properties, being easily absorbed and permeable. These findings suggest that 2-chlorounguinol possesses potential antibacterial activity and could be developed as an antibiotic adjuvant to reduce antimicrobial resistance.     

四季青水煎液体外抗内毒素、抗菌和体内抗炎作用

目的 研究四季青水煎液的抗内毒素、抗菌和抗炎作用,揭示四季青清热解毒作用的药效学特点。方法 采用体外鲎试剂凝集实验方法检测其抗内毒素作用;采用琼脂二倍稀释法测定四季青水煎液以及与头孢噻肟、左氧氟沙星和庆大霉素联合使用时对25株甲氧西林敏感金黄色葡萄球菌(MSSA)、耐甲氧西林金黄色葡萄球菌(MRSA)、产超广谱β-内酰胺酶(extended-spectrum β-lactamase, ESBLs)大肠埃希菌、非产ESBLs大肠埃希菌和铜绿假单胞菌的最低抑菌浓度(minimum inhibitory concentration, MIC);采用二甲苯致小鼠耳廓炎症肿胀法观察其抗炎作用。结果 四季青水煎液在生药浓度6.25~100mg/mL时具有抗内毒素作用;对受试菌株MSSA、MRSA的MIC范围均为8~33mg/mL,对产ESBLs大肠埃希菌及非产ESBLs大肠埃希菌的MIC范围均为33~>133mg/mL,对铜绿假单胞菌的MIC为33~133mg/mL;与头孢噻肟、左氧氟沙星和庆大霉素联合使用时抗菌活性有相加作用,分级抑菌浓度(fractional inhibitory concentration, FIC)指数范围为0.5相似文献   

In vitro antibacterial activity of prulifloxacin,a new oral fluoroquinolone

We compared antibacterial activity of NM394, which is the active metabolite of a prodrug of new fluoroquinolone prulifloxacin (PUFX), against clinical isolates of bacteria with those of ciprofloxacin (CPFX), levofloxacin (LVFX), gatifloxacin (GFLX), tosufloxacin (TFLX) and fleroxacin (FLRX). 1. NM394 showed a broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria. 2. MIC80 of NM394 for methicillin-sensitive Staphylococcus aureus, Streptococcus pneumoniae and Enterococcus faecalis were 0.5 microgram/ml, 2 micrograms/ml and 4 micrograms/ml, respectively. MIC80 of NM394 for Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae was lower than 0.06 microgram/ml. MIC80 of NM394 for Serratia marcescens and Pseudomonas aeruginosa were 0.25 microgram/ml and 2 micrograms/ml, respectively. 3. Short-time bactericidal activity of NM394 against P. aeruginosa was stronger than those of CPFX, GFLX, LVFX and TFLX. 4. Short-time bactericidal activity of NM394 at Cmax concentration against 12 strains of P. aeruginosa was stronger than those of CPFX, LVFX, GFLX and TFLX.     

Comparative assessment of prurifloxacin, sparfloxacin, gatifloxacin and levofloxacin in the rabbit model of proarrhythmia

The administration of certain quinolone antibiotics has been associated with a prolongation of the QT interval on electrocardiogram, and in rare cases ventricular arrhythmias such as torsades de pointes. In this in vivo study using a rabbit arrhythmia model, we assessed the proarrhythmic effects and changes in the QT interval elicited by the administration of NM394 (UFX), an active metabolite of the new quinolone antibiotic prulifloxacin, and three representative quinolones, sparfloxacin (SPFX), gatifloxacin (GFLX) and levofloxacin (LVFX). Chloralose-anesthetized rabbits were co-administered a continuous infusion of methoxamine (15 microg/kg/min) together with NaOH (vehicle, 0.2 mol/L), SPFX (2, 3, 4 mg/kg/min), GFLX (4 mg/kg/min), LVFX (4 mg/kg/min) or UFX (4 mg/kg/min) via the ear vein, and then the effects on electrocardiogram were examined. SPFX and GFLX both prolonged the QT and QTc intervals. GFLX also induced premature ventricular contractions in all 6 rabbits that received it, and subsequently it induced torsades de pointes (TdP) in 3 of the 6 rabbits. SPFX infused at the dose of 4 mg/ kg/min induced conduction blocks without inducing TdP, whereas that infused at the lower dose of 3 mg/ kg/min induced both conduction blocks and TdP. The infusions with LVFX and UFX did not elicit remarkable prolongations in the QT interval, and none of the animals infused with the agents developed arrhythmia. These findings suggested that LVFX and UFX were less potent than SPFX and GFLX in prolonging the QT interval and inducing life-threatening arrhythmias.     

Small molecules with antimicrobial activity against E. coli and P. aeruginosa identified by high-throughput screening

BACKGROUND AND PURPOSE: New antimicrobials are needed because of the emergence of organisms that are resistant to available antimicrobials. The purpose of this study was to evaluate a high-throughput screening approach to identify antibacterials against two common disease-causing bacteria, and to determine the frequency, novelty, and potency of compounds with antibacterial activity. EXPERIMENTAL APPROACH: A high-throughput, turbidometric assay of bacterial growth in a 96-well plate format was used to screen a diverse collection of 150,000 small molecules for antibacterial activity against E. coli and P. aeruginosa. The statistical Z'-factor for the assay was > or = 0.7. KEY RESULTS: Screening for inhibition of E. coli growth gave a 'hit' rate (> 60% inhibition at 12.5 microM) of 0.025%, which was more than 5-fold reduced for P. aeruginosa. The most potent antibacterials (EC50 < 0.5 microM) were of the nitrofuran class followed by naphthalimide, salicylanilide, bipyridinium and quinoazolinediamine chemical classes. Screening of > 250 analogs of the most potent antibacterial classes established structure-activity data sets. CONCLUSIONS AND IMPLICATIONS: Our results validate and demonstrate the utility of a growth-based phenotype screen for rapid identification of small-molecule antibacterials. The favourable efficacy and structure-activity data for several of the antibacterial classes suggests their potential development for clinical use.