In vitro activity of piperacillin/tazobactam against isolates from patients enrolled in clinical trials

The in vitro activity of piperacillin alone or titrated with a constant concentration of 4 mug/ml tazobactam was evaluated against 3962 baseline pathogens isolated from 1899 patients enrolled in 9 clinical trial studies in North America. Tazobactam increased susceptibility rates of piperacillin for Enterobacteriaceae from 81% to 96%, Staphylococcus (methicillin susceptible) spp. from 6% to 100%, Bacteroides fragilis group from 79% to >99% and Haemophilus from 85% to 98%. The excellent activity of piperacillin against Pseudomonas, Streptococcus and Enterococcus was maintained in the presence of tazobactam. Overall piperacillin/tazobactam had better activity than ticarcillin/clavulanic acid, ceftazidime, and in general equaled the activity of imipenem. The excellent in vitro, extended-spectrum activity of piperacillin/tazobactam suggests its utility for various infections.     

In vitro activity of coumermycin alone or in combination against Staphylococcus aureus and Staphylococcus epidermidis

The in vitro activity of coumermycin was tested against oxacillin-susceptible and resistant strains of Staphylococcus aureus and Staphylococcus epidermidis, and compared with that of penicillin G, oxacillin, minocyclin, erythromycin, vancomycin, teicoplanin, rifampicin and LM 427. The MICs were measured using the agar dilution method with an inoculum of 10(5) cfu/spot. Coumermycin was the most active antibiotic with MIC90 of 0.025-0.2 mg/l. The MICs of coumermycin remained unchanged by further incubation for 48 h. The combination of coumermycin with ciprofloxacin, an inhibitor of subunit A of the DNA gyrase, was studied by the time-kill curve method and resulted in a synergistic effect when subinhibitory concentrations of either antibiotic were used. The combination of coumermycin with rifampicin or LM 427 was antagonistic.     

哌拉西林／舒巴坦对临床分离菌的体外抗菌作用

目的 对哌拉西林／舒巴坦进行体外抗菌活性研究。方法 采用琼脂二倍稀释法测定最低抑菌浓度,采用肉汤稀释法测定最低杀菌浓度,并对其影响因素进行测定。结果 本品对肠杆菌科细菌、非发酵菌、葡萄球菌、粪肠球菌抗菌活性均低于亚胺培南,对不产酶流感嗜血杆菌和粘膜莫拉氏菌抗菌活性高于亚胺培南2－16倍。对肺炎链球菌和嗜麦芽黄单胞菌的抗菌活性同本次所研究的所有对照药。对临床常见5种致病菌（铜绿假单胞菌、大肠埃希氏菌、肺炎克雷伯氏菌、金葡球菌和粪肠球菌）的MIC和MBC非常接近,差异在0－2之间,表明本品为一杀菌剂。     

In vitro interaction of tazobactam/piperacillin combined with aminoglycosides against Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli AND Staphylococcus aureus

The in vitro combination effect of tazobactam/piperacillin (TAZ/PIPC) with aminoglycosides (amikacin (AMK) and isepamicin (ISP)) were investigated by the checkerboard dilution method against PIPC-resistant and TAZ/PIPC-susceptible Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli and Methicillin-sensitive Staphylococcus aureus (MSSA). The following results were obtained. 1. The combination of TAZ/PIPC with AMK showed synergistic effect for 66.7% of P. aeruginosa and 9.1% of K. pneumoniae and additive effect for 76.9% of E. coli and 74.1% of MSSA. The antagonistic effect of TAZ/PIPC with AMK was not demonstrated for all tested strains. 2. The combination of TAZ/PIPC with ISP showed synergistic effect for 61.9% of P. aeruginosa and 22.7% of K. pneumoniae and additive effect for 84.6% of E. coli and 66.7% of MSSA. The antagonistic effect of TAZ/PIPC with ISP was not demonstrated for all tested strains. In conclusion, these results suggest that the combination therapies of TAZ/PIPC with aminoglycosides are useful for the clinical treatment of sepsis caused by above four species.     

哌拉西林/舒巴坦对非发酵菌体外抗菌活性研究

目的 评价哌拉西林/舒巴坦对非发酵菌体外抗菌活性.方法 采用微量肉汤稀释法测定哌拉西林/舒巴坦对细菌的体外抗菌作用.结果 北京、天津、广州、哈尔滨和重庆5个城市的8家医院共收集菌株809株.对于所有铜绿假单胞菌,在8种测试药物中,哌拉西林/舒巴坦的敏感率最高(71.9%),而亚胺培南、头孢吡肟、头孢他啶、头孢哌酮/舒巴坦敏感率都低于50%.对于亚胺培南不敏感的铜绿假单胞菌,哌拉两林/舒巴坦敏感率仍可达55.8%.对于碳青霉烯敏感的鲍曼不动杆菌,哌拉西林/舒巴坦和头孢哌酮/舒巴坦敏感率最高,分别为71.0%和73.0%.对于嗜麦芽寡养单胞菌,26%和20%的菌株对哌拉西林/舒巴坦和哌拉两林/三唑巴坦的MIC≤16μg/mL.对于洋葱伯克霍尔德菌,69%的菌株对哌拉两林/舒巴坦的MIC≤16μg/mL.对于黄杆菌属和产碱杆菌属,哌拉西林/舒巴坦、头孢哌酮/舒巴坦和哌拉西林/三唑巴坦3种酶抑制剂复合制剂敏感率最高,分别为70.2%、63.2%、57.9%和94.4%、94.4%、91.7%.结论 哌拉西林/舒巴坦对于多种非发酵菌具有良好的体外抗菌活性.对碳青霉烯不敏感的铜绿假单胞菌具备一定的抗菌优势,哌拉西林/舒巴坦是经验性治疗非发酵菌感染(包括复数菌感染)的的适宜选用药物之一.     

In vitro synergistic interaction of 5-O-methylglovanon and ampicillin against ampicillin resistant Staphylococcus aureus and Staphylococcus epidermidis isolates

5-O-methylglovanon (5-O-MG) is a bioactive compound that was first isolated and characterized from Glycosmis plants. In this study, we found that chemically synthesized 5-O-MG has antimicrobial ability against eleven clinical ampicillin resistant Staphylococcus aureus and S. epidermidis isolates. The MICs of 5-O-MG against the S. aureus and S. epidermidis isolates were 12.5–50 μg/mL and 25–50 μg/mL, respectively. In combination with ampicillin, a synergistic interaction between 5-O-MG and ampicillin against the eleven resistant Staphylococcus isolates was observed, with fractional inhibitory concentration indices of 0.03–0125. Moreover, the anti-staphylococcal activity of 5-O-MG in combination with ampicillin was comparable with that of clavulanic acid in combination with ampicillin. The drug combination had no antagonistic effects when tested against any of the strains. Time-killing assays confirmed the synergy between 5-O-MG and ampicillin (p < 0.01). The combination of these two agents yielded greater than a 2 log₁₀ cfu/mL decrease in comparison with 5-O-MG or ampicillin alone. These findings suggest that 5-O-MG is a promising compound with the potential for future anti-staphylococcal drug development.     

In vitro activity of tigecycline against quinolone-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci

Tigecycline is a glycylcycline with promising broad-spectrum activity, including resistant Gram-positive organisms. This study characterizes in vitro activity of tigecycline against quinolone-resistant Streptococcus pneumoniae (QRSP), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE). An in vitro pharmacodynamic model generated specific bacterial kill profiles for tigecycline against clinical isolates of QRSP, MRSA and VRE. Tigecycline produced a 6.6 log total reduction and cleared QRSP from the pharmacodynamic model by 18 h. Tigecycline and vancomycin were unable to achieve 3-log reductions in the MRSA and VRE isolates; log reductions in MRSA and VRE were 1.5 and 1.2 logs for tigecycline and 2.8 and zero for vancomycin, respectively. Area under the concentration time curve to minimum inhibitory concentration (AUC/MIC) values for tigecycline ranged from 79 to 158 microg h/mL and tigecycline concentrations remained above the MIC (T>MIC) throughout the simulated dosing interval. Tigecycline showed in vitro activity against the QRSP, MRSA and VRE isolates studied. Low MIC values, prolonged elimination half-life and the associated post-antibiotic effect (PAE) observed with tigecycline are desirable attributes that make it a potentially attractive option for treating resistant Gram-positive organisms.     

In vitro activity of minocycline combined with fosfomycin against clinical isolates of methicillin-resistant Staphylococcus aureus

This study aimed to evaluate the in vitro activity of minocycline combined with fosfomycin against isolates of methicillin-resistant Staphylococcus aureus (MRSA). A total of 87 clinical isolates of MRSA collected from three Chinese hospitals were included in the study. The checkerboard method with determination of the fractional IC index (FICI) was used to determine whether antibiotic combinations act synergistically against these isolates. The susceptibility results for minocycline and fosfomycin were interpreted according to the most relevant criteria. The results demonstrated the following interactions: 76 isolates (87.4%) showed synergistic interactions (FICI0.5) and 11 isolates (12.6%) showed indifferent interactions (0.5相似文献   

哌拉西林／舒巴坦对临床分离功的体外抗菌活性研究

目的比较研究哌拉西林、舒巴坦、哌拉西林与舒巴坦不同比例联合及阿莫西林/舒巴坦(21),对临床分离309株需氧菌和30株厌氧菌的体外抗菌活性及其影响因素(研究哌拉西林/舒巴坦(21)对金葡球菌、大肠埃希氏菌和铜绿假单胞菌的的杀菌曲线).方法采用琼脂平板稀释法及肉汤稀释法测定MIC值,Nitrocefin纸片法测定细菌产生的β-内酰胺酶,时间杀菌曲线采用肉汤10倍稀释法.结果对临床分离的339株需氧菌及厌氧菌体外抗菌活性研究结果显示,哌拉西林及其与舒巴坦联合时,对革兰氏阳性球菌及厌氧菌的体外抗菌活性MIC5o为1～4μg/ml,MIC90多数低于128μg/ml,优于革兰氏阴性杆菌,其MIC50为1～128μg/ml,MIC90多数高于128μg/ml;单用舒巴坦对各种细菌的体外抗菌活性极差,多数菌的MICso及MIC90分别为64及256μg/ml.对革兰氏阴性杆菌及厌氧菌,哌拉西林与舒巴坦联合时体外抗菌活性明显优于单用哌拉西林;对于革兰氏阳性球菌,哌拉西林联合舒巴坦后体外抗菌活性改善不如革兰氏阴性杆菌及厌氧菌.哌拉西林对产酶株的MIC高于非产酶株,联合舒巴坦后,产酶株MIC降低而非产酶株MIC变化不明显.不同比例联合的体外抗菌活性比较发现,以哌拉西林/舒巴坦21联合时效果较好.哌拉西林与舒巴坦21联合时,对多数临床分离菌的体外抗菌活性与阿莫西林/舒巴坦(21)的体外抗菌活性相当.本研究中,I临床分离细菌对哌拉西林的耐药率以假单胞菌属最高,达61.5%,其次是肠杆菌属细菌及大肠埃希氏菌,分别为50.8%、50.0%.哌拉西林联合舒巴坦后,所有细菌的耐药率明显下降.体外杀菌效果研究表明,当哌拉西林联合舒巴坦21时,4×MIC浓度作用于金葡球菌、大肠埃希氏菌及铜绿假单胞菌后,细菌数均随时间延长而呈指数级减少,在作用于8h细菌均被杀灭.1×MIC及2×MIC作用于以上细菌后,杀菌效果不及4×MIC.各种细菌的体外抗菌活性主要受培养基pH值及接种菌量的影响,几乎不受小牛血清白蛋白浓度的影响.结论哌拉西林/舒巴坦对β-内酰胺酶产生菌株的体外抗菌活性优于哌拉西林,以21联合效果最好,杀菌效果以4×MIC浓度最好,体外抗菌活性受培养基pH值及接种量的影响.     

哌拉西林/舒巴坦对临床分离菌的体外抗菌活性研究

目的　比较研究哌拉西林、舒巴坦、哌拉西林与舒巴坦不同比例联合及阿莫西林 /舒巴坦 (2∶1) ,对临床分离 3 0 9株需氧菌和 3 0株厌氧菌的体外抗菌活性及其影响因素 (研究哌拉西林 /舒巴坦 (2∶1)对金葡球菌、大肠埃希氏菌和铜绿假单胞菌的的杀菌曲线 )。方法　采用琼脂平板稀释法及肉汤稀释法测定MIC值 ,Nitrocefin纸片法测定细菌产生的 β 内酰胺酶 ,时间杀菌曲线采用肉汤 10倍稀释法。结果　对临床分离的3 3 9株需氧菌及厌氧菌体外抗菌活性研究结果显示 ,哌拉西林及其与舒巴坦联合时 ,对革兰氏阳性球菌及厌氧菌的体外抗菌活性MIC50 为 1～ 4μg/ml,MIC90 多数低于 12 8μg/ml,优于革兰氏阴性杆菌 ,其MIC50 为 1～12 8μg/ml ,MIC90 多数高于 12 8μg/ml;单用舒巴坦对各种细菌的体外抗菌活性极差 ,多数菌的MIC50 及MIC90 分别为 64及 2 5 6μg/ml。对革兰氏阴性杆菌及厌氧菌 ,哌拉西林与舒巴坦联合时体外抗菌活性明显优于单用哌拉西林 ;对于革兰氏阳性球菌 ,哌拉西林联合舒巴坦后体外抗菌活性改善不如革兰氏阴性杆菌及厌氧菌。哌拉西林对产酶株的MIC高于非产酶株 ,联合舒巴坦后 ,产酶株MIC降低而非产酶株MIC变化不明显。不同比例联合的体外抗菌活性比较发现 ,以哌拉西林 /舒巴坦 2∶1联合时效果较好。     

In vitro susceptibilities of clinical isolates of Staphylococcus aureus

In vitro susceptibilities of 350 strains of Staphylococcus aureus to ampicillin (ABPC), methicillin (DMPPC), cloxacillin (MCIPC), cefazolin (CEZ), cefmetazole (CMZ), cefmenoxime (CMX), latamoxef (LMOX) and 5 non-beta-lactam antimicrobial agents were determined according to the standard method of Japan Society of Chemotherapy. Frequencies of the appearance of resistant organisms (MIC greater than or equal to 12.5 micrograms/ml) to beta-lactam antibiotics were 45% for ABPC, 27% for DMPPC, 11% for MCIPC, 24% for CEZ, 15% for CMZ, 36% for CMX and 51% for LMOX. To non-beta-lactam antimicrobial agents, resistant strains appeared at 31% to gentamicin, 15% to amikacin, 0.6% to minocycline (MINO), 1% to norfloxacin (NFLX) and 65% to fosfomycin (FOM). More than 80% of DMPPC-resistant strains were also resistant to LMOX, CMX, ABPC, FOM, and CEZ, but most of those were susceptible to MINO and NFLX. Incidence of DMPPC-CEZ resistant S. aureus was 23% of the 350 strains tested. As stated above, multiply resistant strains of S. aureus are present throughout different hospitals in Okinawa.     

In vitro antimicrobial activity of telavancin against methicillin-resistant Staphylococcus aureus clinical isolates from Japan (2006)

In vitro antimicrobial activity of telavancin, a rapidly bactericidal lipoglycopeptide, was evaluated against 1500 strains of MRSA recently isolated in Japan. Telavancin had potent activity, with MIC values that ranged from 0.12 microg/ml to 0.5 microg/ml and a MIC90 value of 0.5 microg/ml. The MIC90s of vancomycin and linezolid were 1.0microg/ml and 2 microg/ml, respectively. No vancomycin intermediate resistant or vancomycin-resistant MRSAs were detected in this surveillance study.     

异帕米星对金葡菌的体外抗菌活性分析

目的 观察异帕米星（isepamicin）对金葡菌的体外抗菌活性，为临床用药提供参考。方法 使用纸片扩散法检测异帕米星和其他12种抗生素对152株金葡菌的敏感性，并对结果进行分析。结果 敏感率最高的4种抗生素依次为万古霉素（100％）、异帕米星（93．4％）、氯霉素（92．1％）、复方磺胺甲噁唑（89．5％）。异帕米星对MRSA的敏感率为91．7％；对MSSA的敏感率为100％。结论 异帕米星对金葡菌有良好的抗菌活性。     

美罗培南对临床分离致病菌的体外抗菌活性研究

目的评价美罗培南的体外抗菌活性方法采用琼脂二倍稀释法测定美罗培南及对照药亚胺培南、头孢吡肟、头孢他啶、头孢哌酮／舒巴坦、环内沙星对412株临床分离致病菌的体外抗菌活性。结果显示，对多种革兰氏阴性菌，美罗培南均有较强的抗菌作用，其抗菌作用强于对照药亚胺培南、头孢吡肟、头孢他啶、环丙沙星、奈替米星；对大肠埃希氏菌、克雷泊氏菌属、产气肠杆菌、志贺氏菌属、沙门氏菌属、柠檬酸菌属、变形菌属、沙雷氏菌属MIC90≤0．008～0．25mg/L，是亚胺培南MIC9o的1／4～1／16，对阴沟肠杆菌、不动杆菌属与亚胺培南的抗菌作用相当，分别为0．25、0．5mg／L：对流感嗜血杆菌美罗培南的MIC90为0．125mg／L，是亚胺培南的1／16，是第四代头孢菌素头孢吡肟的1/4：对铜绿假单孢菌美罗培南的MIC90为4mg／L，低于亚胺培南8mg／L。对革兰氏阳性菌作用稍差于亚胺培南，优予其他4种对照药。     

不同配比的头孢呋辛/三唑巴坦对临床分离革兰阴性菌的体外药效学研究

目的比较不同配比头孢呋辛／三唑巴坦（cefuroxime／tazobactam，1：1、2：1、4：1）对临床分离致病菌的体外抗菌活性，为新药研发提供实验依据。方法以平皿二倍稀释法测定MIC值，nitrocefin纸片法测定产酶株，双纸片法筛选ESBLs菌株。结果对本次研究收集的2004年1月～2006年1月共482株致病菌进行MIC测定，其中84．85％的菌株产β-内酰胺酶，36．31％产生ESBLs。不同配比的头孢呋辛／三唑巴坦联合制剂对革兰阴性菌的抗菌作用较强，尤其对大肠埃希菌与克雷伯菌属，头孢呋辛／三唑巴坦（1：1）的MIC90值分别从〉256和〉256μg／ml下降至32和64μg／ml，部分细菌，尤其是产ESBLs菌株的耐药率明显下降。头孢呋辛／三唑巴坦3个配比中以1：1配比的抗菌作用最强。头孢哌酮／舒巴坦和哌拉西林／三唑巴坦对革兰阴性菌具有较好的抗菌活性。结论头孢呋辛／三唑巴坦（1：1）为一强效广谱杀菌药物，对产ESBLs菌具有较好的抗菌活性。本次研究中孢呋辛／三唑巴坦1：1配比的MIC50与MIC90值都低于2：1和4：1两个配比，对产超广谱β-内酰胺酶的大肠埃希菌和肺炎克雷伯菌的抗菌活性最强。     

不同配比头孢呋辛与他唑巴坦的体外抗菌活性

目的评价不同配比头孢呋辛／他唑巴坦及单剂对临床分离致病菌的体外抗菌活性。方法以平皿二倍稀释法对22种661株致病菌测定MIC值；以试管二倍稀释法测定MBC值；以活菌计数法绘制杀菌曲线。结果661株致病菌中，72．01％产β内酰胺酶；联合制剂明显增强了对革兰阴性菌的抗菌作用；酶抑制剂他唑巴坦可明显提高头孢呋辛对耐药菌的抗菌作用，MIC90值下降到单药的1／8～1／30，耐药率减少了12％～80％。在碱性条件下，使联合制剂抗菌作用增强；而酸性环境，可减弱其抗菌作用；4个配比中，1：1配比抗菌作用最强。结论头孢呋辛／他唑巴坦（1：1）为一强效广谱杀菌药。     

香叶醇体外抗MRSA活性研究

目的 通过体外抑菌实验,评价香叶醇单独使用以及与3种β-内酰胺类抗生素(阿莫西林、头孢氨苄及头孢吡肟)联合使用对耐甲氧西林金黄色葡萄球菌(methicillin resistant Staphylococcus aureus, MRSA)的抑制效果。方法 采用微量稀释法测定香叶醇与3种β-内酰胺类抗生素的最低抑菌浓度(minimum inhibitory concentration, MIC)及最低杀菌浓度(minimum bactericidal concentration, MBC);微量棋盘法测定香叶醇与3种β-内酰胺类抗生素的分级抑菌浓度指数(fractional inhibitory concentration, FIC)。结果与结论 香叶醇具有明显的体外抗MRSA活性,MIC和MBC分别为0.34~0.69mg/mL和0.69~10.76mg/mL。联合药敏试验发现香叶醇与3种β-内酰胺类抗生素联合使用FIC指数集中分布在≤0.5和0.5~1;能够增强β-内酰胺类抗生素的活性,降低其用量,使其MIC50和MIC90降低为单独用药的1/8~1/4和1/4~1/2。