利奈唑胺、去甲万古霉素等抗菌药物对耐甲氧西林金黄色葡萄球菌的抗菌活性

目的:研究北京市三家医院耐甲氧西林金黄色葡萄球菌(MRSA)耐药现状,评价利奈唑胺、去甲万古霉素等药物的抗菌活性。方法:收集解放军总医院、北京医院、北京协和医院三家医院分离的非重复MRSA111株,头孢西丁纸片法确认MRSA,采用琼脂稀释法测定抗菌药物的最低抑菌浓度(MIC)。结果:111株MRSA,对β-内酰胺类的耐药率为100%,对红霉素的耐药率为92.8%,对氨基糖苷类(奈替米星、庆大霉素)的耐药率为99.1%,对氟喹酮类(加替沙星、莫西沙星、左氧氟沙星)的耐药率为91.9%~99.1%,对氯霉素的耐药率为3.6%,对去甲万古霉素、利奈唑胺全部敏感,对去甲万古霉素MIC50和MIC90分别为0.5和1μg/mL,对利奈唑胺的MIC50和MIC90均为2μg/mL。结论:北京三家医院分离的MRSA对本研究的大多数抗菌药物均耐药,去甲万古霉素和利奈唑胺对于MRSA有很高的抗菌活性。     

万古霉素联合利奈唑胺体外抑制MRSA活性的探讨

目的:探讨万古霉素联合利奈唑胺体外对耐甲氧西林金黄色葡萄球菌(MRSA)抑菌效应。方法:采用试管二倍稀释法测定万古霉素、利奈唑胺及两者联用时对MRSA抑菌的各自最低抑菌浓度(MIC)值,同时利用棋盘微量稀释法测定不同浓度组合的万古霉素、利奈唑胺抗菌药物对MRSA的最低抑菌浓度,计算相应的联合抑菌指数(FIC)。结果:单用抑制MRSA时,MIC万古霉素为1.563μg/m L,MIC利奈唑胺为0.25μg/m L;当两者联用时,MIC万古霉素、MIC利奈唑胺分别为0.391 0μg/m L、0.312 5μg/m L,联用前后MIC差异有统计学意义(P<0.05),其相应的FIC<0.5。结论:万古霉素与利奈唑胺联用有协同抑菌作用,具有较高的体外抗菌活性,可为有效降低临床细菌耐药率提供新途径。     

利奈唑胺、万古霉素对甲氧西林耐药的金黄色葡萄球菌的防耐药突变体选择浓度的研究

目的：比较利奈唑胺、万古霉素对耐甲氧西林金黄色葡萄球菌的防耐药突变选择能力;研究防耐药突变体选择浓度（MPC）和最低抑菌浓度（MIC）的相关性。方法：采用琼脂微量稀释法测定利奈唑胺、万古霉素对35株耐甲氧西林金黄色葡萄球菌（MRSA）临床分离菌株的MPC和MIC;采用线性回归法比较利奈唑胺、万古霉素对MRSA的MPC和MIC的相关性;结合人体药代动力学数据,预测利夺唑胺、万古霉素对MRSA的防耐药突变体选择能力。结果：利奈唑胺、万古霉素对35株MRSA的MPC90值（抑制90％的细菌发生细菌耐药的最低防耐药突变体选择浓度）分别为16.8μg／mL,选择指数（MPC90／MIC90）均为8。两药对MRSA的MPC和MIC的线性相关系数R^2分别为0．32和0．008。结合两药药代动力学参数,利奈唑胺药物浓度在整个给药间隔落在耐药突变选择窗理论（MSW）中,万古霉素药物浓度在大部分给药间隔落在MPC之上。结论：万古霉素对MRSA的防耐药选择能力强于利奈唑胺;MPC和MIC的相关性差。     

利奈唑胺、替考拉宁和万古霉素等抗菌药物对常见需氧革兰阳性球菌的体外抗菌活性

目的评价利奈唑胺、替考拉宁和万古霉素等抗菌药物的体外抗菌活性。方法采用琼脂稀释法对临床收集的132株革兰阳性球菌进行抗菌活性测定,记录其各自的MIC并进行比较。结果利奈唑胺、替考拉宁及万古霉素3药对革兰阳性球菌均有较大抗菌活性,敏感率均为100%,包括其中的耐甲氧西林葡萄球菌和青霉素中介肺炎链球菌均有良好抗菌作用。3药在部分革兰阳性球菌的抗菌作用中与利福平相仿,但比氨基糖苷类抗生素和氟喹诺酮类抗菌药强。在对甲氧西林敏感金葡萄的抗菌活性中,替考拉宁的MIC90均为利奈唑胺和万古霉素的4倍;在对甲氧西林敏感凝固酶阴性葡萄球菌的抗菌活性中,替考拉宁的MIC90分别均为利奈唑胺和万古霉素的8倍;而在青霉素敏感和中介肺炎链球菌的抗菌活性中,替考拉宁的MIC90为利奈唑胺的1/16,为万古霉素的1/8;在肠球菌属的抗菌活性中,万古霉素的MIC90分别为利奈唑胺的2倍,是替考拉宁的4倍和8倍。结论利奈唑胺、替考拉宁以及万古霉素等三药对革兰阳性球菌有较大的抗菌作用,对部分革兰阳性菌的抗菌作用与利福平相仿,但比其他如氨基糖苷类抗生素和氟诺酮类抗菌药更优,是临床革兰阳性球菌严重感染的有效药物。     

利奈唑胺对h-VRS体外抗菌活性研究

目的 了解利奈唑胺对异质性耐万古霉素葡萄球菌(heterogeneous vancomycin resistant Staphylococci,h-VRS)体外抗菌活性.方法 采用含万古霉素脑心浸液琼脂(BHIA)筛选h-VRS,采用KB法检测万古霉素、利奈唑胺对其原代菌株及h-VRS的抑菌圈直径,琼脂稀释法检测万古霉素、利奈唑胺对h-VRS的MICs值,并将检测结果分别与原代检测结果相比较.结果 h-VRS的检出率为2.6%;KB法与琼脂稀释法检测原代菌株及h-VRS对万古霉素的药敏实验结果不完全符合,KB法不能检出h-VRS;利奈唑胺对原代菌株及h-VRS的MIC均≤21 μg/ml,没有检出对利奈唑胺呈中介或耐药株.KB法与琼脂稀释法检测利奈唑胺对原代菌株及h-VRS的药敏结果完全符合.结论 利奈唑胺对h-VRS具有较强的体外抗菌活性,葡萄球菌对万古霉素和利奈唑胺的耐药性之间无交叉耐药现象.     

利奈唑胺对人多形核细胞吞噬作用的影响

利奈唑胺是口服唑烷酮类抗菌药 ,主要抑制细菌蛋白合成。许多常见革兰氏阳性菌 (如金黄色葡萄球菌、肠球菌属、肺炎链球菌 )对抗菌剂耐药性不断增加 ,研发新的抗革兰氏阳性菌的药物迫在眉睫。利奈唑胺对革兰氏阳性菌具有广谱抗菌活性 ,包括甲氧西林耐药金黄色葡萄球菌、头孢菌素耐药肺炎球菌、万古霉素耐药粪肠球菌和屎肠球菌 ,以及厌氧菌如梭菌属、消化链球菌属、普雷沃氏菌属 ,对大多敏感菌株有抑菌作用 ,但对肺炎球菌、脆弱拟杆菌和产气荚膜梭菌有杀菌作用。许多药物在组织中对不能达到特定病原菌的MIC ,但低于特定病原菌MIC浓度的…     

利奈唑胺对万古霉素敏感及耐药屎肠球菌的抗菌活性

目的 评价利奈唑胺对临床分离万古霉素敏感及耐药屎肠球菌的体外抗菌活性.方法 多重PCR法鉴定屎肠球菌万古霉素耐药基因类型,平皿二倍稀释法测定利奈唑胺等11种抗菌药物MIC值.结果 75株临床分离万古霉素耐药屎肠球菌均携带vanA基因.万古霉素敏感及耐药屎肠球菌对利奈唑胺均敏感,MIC范围1～2mg/L.与红霉素、氨苄西林、左氧氟沙星和利福平相比,万古霉素敏感及耐药屎肠球菌的耐药率均在80%以上.万古霉素敏感屎肠球菌对高浓度庆大霉素、高浓度链霉素、四环素和氯霉素的耐药率分别为80.2%、13.9%、38.6%和37.6%;万古霉素耐药屎肠球菌对上述4种药物的耐药率分别为64.5%、8.0%、18.5%和5.3%.结论 利奈唑胺对我国临床分离万古霉素敏感和耐药屎肠球菌均具有很好的体外抗菌活性.     

2743株革兰阳性菌的临床分离及耐药性分析

目的探讨我院2013年革兰阳性菌的临床分离及耐药情况。方法常规方法培养、分离革兰阳性菌,用纸片扩散法、Etest法或全自动细菌分析仪测定细菌对不同抗菌药物的敏感性,采用2013年版CLSI标准判读结果。结果共分离2 743株革兰阳性菌,葡萄球菌属占43.3%,肠球菌属占35.6%,链球菌属占15.2%。金黄色葡萄球菌、表皮葡萄球菌和溶血葡萄球菌对苯唑西林耐药率分别为46.9%,81.4%和94.2%,未发现万古霉素和利奈唑胺耐药葡萄球菌。屎肠球菌对利奈唑胺和万古霉素耐药率分别为0.4%和0.5%,粪肠球菌对利奈唑胺耐药率为0.3%,未发现万古霉素耐药粪肠球菌。结论万古霉素、利奈唑胺和替考拉宁对葡萄球菌、肠球菌和链球菌仍有很高抗菌活性,甲氧西林耐药葡萄球菌比率较高。     

比较6种氟喹诺酮类药物对金黄色葡萄球菌的防耐药变异浓度

目的比较6种氟喹诺酮类药物对临床分离金黄色葡萄球菌耐药突变体的选择能力。方法用呼吸道标本,选择对苯唑西林、环丙沙星敏感的金黄色葡萄球菌36株,采用标准琼脂二倍稀释法、标准琼脂平板稀释法,测定6种氟喹诺酮类药物对金黄色葡萄球菌的MIC、MPC。结果 MPC值比较,莫西沙星最低;而环丙沙星最高。选择指数(MPC90/MIC90)较低有如下4种:莫西沙星、卡屈沙星、加替沙星和帕珠沙星,均为2。6种药物MPC90值与其体内药动学参数比较,莫西沙星和卡屈沙星小于其Cmax。结论莫西沙星、卡屈沙星和加替沙星对金葡菌的MPC值较低,突变选择窗范围相对较窄。     

利奈唑胺对耐甲氧西林金黄色葡萄球菌细菌生物膜的抑制与消除活性及体内外抗菌活性研究

目的：系统性评价利奈唑胺对2013~2014年耐甲氧西林金黄色葡萄球菌（MRSA）临床分离株细菌生物膜（BBF）的活性及体内外抗菌效果。方法：体外试验测定最低抑菌浓度（MIC）;最低杀菌浓度（MBC）;最小抑制BBF浓度（MBIC）和最低BBF消除浓度（MBEC）;活菌计数法绘制时间-杀菌曲线（KCs）;体内试验采用小鼠MRSA全身感染模型,尾静脉给药保护小鼠后测定半数有效剂量（ED50）;建立免疫低下小鼠MRSA大腿感染模型,记录尾静脉给药24 h后大腿组织菌量的变化。结果：利奈唑胺对2013~2014年临床分离的60株MRSA均敏感;对金黄色葡萄球菌BBF的MBIC值与万古霉素相当,敏感性显著高于阿莫西林;体内试验中,利奈唑胺对全身感染小鼠有很好的治疗效果,ED50小于万古霉素与阿莫西林;对免疫低下MRSA大腿感染模型小鼠的保护作用也要优于万古霉素和阿莫西林。结论：利奈唑胺对2013~2014年分离的MRSA临床菌株体内外活性均较高,尤其对MRSA的细菌生物膜也显示了极强的抑制作用。     

2007-2009年金黄色葡萄球菌对万古霉素MIC值变化的研究

目的 逐年分析金黄色葡萄球菌对万古霉素、替考拉宁及利奈唑胺的MIC值变化,评估是否存在万古霉素MIC漂移.方法 收集我院2007-2009年临床分离的金黄色葡萄球菌菌株,头孢西丁纸片法确认MRSA,琼脂稀释法测定MRSA与MSSA菌株对万古霉素、替考拉宁、利奈唑胺及头孢西丁的最低抑菌浓度(MIC),计算MIC50,MIC90,MIC几何均值,敏感率及耐药率.结果 共收集金黄色葡萄球菌菌株184株,这3年的MRSA检出率分别为38.8%、46.7%和53.3%,呈逐年增高的趋势(P<0.005).万古霉素、替考拉宁及利奈唑胺对所有菌株均敏感.MRSA对万古霉素MIC几何均值为1.052、1.06和1.069μg/mL,呈逐年上升趋势(P<0.001),MIC≥1μg/mL菌株比例为68.4%、82.9%和91.6%,呈逐年增高的趋势(P<0.005).利奈唑胺对MRSA菌株几何均值为1.037、1.02和1.266μg/mL,无渐进性上升趋势(P>0.05).替考拉宁对MRSA菌株几何均值为0.747、0.714和0.971μg/mL,无渐进性上升趋势(P>0.05).MRSA对万古霉素的MIC几何均值高于MSSA组,差异具有统计学意义(P<0.01).结论 我院2007-2009年临床分离株MRSA检出率逐年增高,MRSA对万古霉素的MIC几何均值高于MSSA菌株,MRSA的MIC几何均值渐年上升,MIC≥1μg/mL菌株比例逐年增高,存在万古霉素MIC漂移趋势.     

利奈唑胺对临床分离阳性球菌的体外敏感性分析

目的:对比利奈唑胺与万古霉素及其他几种常用抗菌药物对临床分离阳性球菌的体外抗菌活性。方法:按照NCCLS(CLSI)2007纸片扩散法操作标准测定利奈唑胺与其他几种常用抗菌药物的体外抗菌活性。结果:本院分离的耐甲氧西林金黄色葡萄球菌(MRSA)比例较高(79.1%),利奈唑胺、万古霉素、替考拉宁的敏感率均达到100%。耐甲氧西林凝固酶阴性葡萄球菌(MRC-NS)的比例较MRSA高(88.9%),利奈唑胺与万古霉素、替考拉宁活性相当,敏感率均为100%。利奈唑胺对粪肠球菌的活性与万古霉素、替考拉宁相当,对屎肠球菌的活性优于万古霉素和替考拉宁(100%,80.4%,78.1%),对青霉素耐药的肺炎链球菌(PRSP)也表现了优越的抗菌活性。结论:对于MRSA、MRCNS、PRSP、粪肠球菌,利奈唑胺与万古霉素、替考拉宁的活性相当,均为100%的敏感率;对屎肠球菌的抗菌活性优于万古霉素和替考拉宁,是治疗多药耐药阳性球菌感染的新型药物。     

In vitro activity of linezolid,synercid and telithromycin against genetically defined high level fluoroquinolone-resistant methicillin-resistant Staphylococcus aureus

The in vitro activity of levofloxacin, moxifloxacin, gatifloxacin, erythromycin, telithromycin, linezolid, synercid and vancomycin was measured against 36 genetically defined, gyrA/grlA double mutant MRSA clinical strains with an MIC to ciprofloxacin > or = 8 mg/l. The three newer fluoroquinolones tested were more active than ciprofloxacin. Resistance rates for levofloxacin and gatifloxacin were high (44.5 and 36.1%, respectively). All the strains were moxifloxacin-susceptible, though most of them had MICs close to the break point. All the strains were intermediate or resistant to erythromycin and most were also resistant to telithromycin. No strains were resistant to linezolid, synercid or vancomycin (MIC(90): 2, 1 and 2 mg/l, respectively).     

莫西沙星对耐药葡萄球菌生物膜药效学研究

目的：研究莫西沙星对4株临床耐药葡萄球菌生物膜的体外药效学。方法：采用微量肉汤稀释法测定莫西沙星的最低抑菌浓度（Minimal inhibitory concentration,MIC）、最低抑制生物被膜浓度（Minimal biofilm inhibitory concentration,MBIC）和最低摧毁生物被膜浓度（minimal biofilm eradication concentration,MBEC）;测定莫西沙星对细菌生物膜形成量以及存活菌的影响;采用微量稀释棋盘法测定莫西沙星与局部用药瑞他帕林的联合抗生物膜效果。结果：莫西沙星在16~256mg/L的范围内可完全摧毁细菌生物膜;2 × MIC显著降低生物被膜的形成量;100 × MIC可显著降低生物被膜存活菌数;与瑞他帕林的联合抗生物膜分数（fractional biofilm inhibitory concentration,FBIC）均小于1.0。结论：莫西沙星对4株临床耐药葡萄球菌生物被膜具有抑制和摧毁作用,而且与局部用药瑞他帕林具有协同作用。     

In vitro susceptibility of 4903 bacterial isolates to gemifloxacin--an advanced fluoroquinolone

The in vitro activity of gemifloxacin against over 4900 bacterial isolates was determined by microbroth dilution with interpretation in accordance with NCCLS guidelines. Susceptibility results were compared with those for ciprofloxacin, gatifloxacin, levofloxacin and moxifloxacin. Gemifloxacin and the other fluoroquinolones were not affected by either beta-lactamase production or penicillin-resistance in Streptococcus pneumoniae. The MIC90 values for gemifloxacin were: S. pneumoniae 0.063 mg/l; Haemophilus influenzae 0.016 mg/l; Moraxella catarrhalis 0.008 mg/l, methicillin-susceptible Staphylococcus aureus 0.063 mg/l; methicillin-susceptible Streptococcus pyogenes 0.031 mg/l; Enterobacteriaceae 0.031-0.16 mg/l; Pseudomonas aeruginosa 4 mg/l; Neisseria meningitidis 0.008 mg/l. The MIC90 for gemifloxacin was lower than those for the other quinolones tested against S. pneumoniae (ciprofloxacin 2-4 mg/l, gatifloxacin 0.5 mg/l, levofloxacin 1-2 mg/l, moxifloxacin 0.25 mg/l). This study confirms the enhanced potent activity of gemifloxacin against Gram-positive pathogens, its broad-spectrum, Gram-negative activity and indicates that gemifloxacin is likely to have an important role in treating patients with Gram-positive and/or Gram-negative infections.     

In vitro efficacy of antimicrobial agents against high-inoculum or biofilm-embedded meticillin-resistant Staphylococcus aureus with vancomycin minimal inhibitory concentrations equal to 2 μg/mL (VA2-MRSA)

Minimal inhibitory concentration (MIC) creep in meticillin-resistant Staphylococcus aureus (MRSA) isolates has been observed in recent years. The potential roles of vancomycin-based combination regimens as well as linezolid and tigecycline against five clinical MRSA isolates with vancomycin MICs of 2 μg/mL (VA2-MRSA) were evaluated and compared in vitro. Antimicrobial susceptibility was studied by the agar dilution method. Anti-MRSA activities of linezolid, tigecycline, vancomycin, minocycline, rifampicin and fosfomycin alone as well as of three vancomycin-based combinations were studied by time-kill method and using a biofilm model. When VA2-MRSA at an inoculum of 1 × 10⁵ colony-forming units (CFU)/mL was incubated with vancomycin, tigecycline, linezolid or rifampicin alone, bactericidal activity lasted for 48 h in time-kill analysis. At a higher inoculum of 1 × 10⁷ CFU/mL, only linezolid demonstrated a bacteriostatic effect at 24 h and the inhibitory activity lasted for 36 h. However, bacterial growth was inhibited ≥2 log₁₀ at 24 h and was even undetectable at 48 h with vancomycin plus fosfomycin or rifampicin. In biofilm studies, vancomycin plus fosfomycin or minocycline at susceptible breakpoint concentrations demonstrated an enhanced antibacterial effect comparable with linezolid and better than tigecycline. In conclusion, vancomycin plus fosfomycin or rifampicin exhibited a synergistic and better antibacterial effect than linezolid or tigecycline alone against high-inoculum planktonic VA2-MRSA. Vancomycin plus fosfomycin or minocycline compared with linezolid exhibited a similar inhibitory effect, better than tigecycline alone, against biofilm-embedded VA2-MRSA. Evaluating the toxicity and efficacy of high-dose vancomycin monotherapy for VA2-MRSA, the fosfomycin combination exhibited a rapid killing effect in both conditions and may provide another therapeutic choice.     

溶葡萄球菌酶对耐甲氧西林金黄色葡萄球菌的体外抗菌活性

目的 :探讨溶葡萄球菌酶对万古霉素低敏耐甲氧西林金黄色葡萄球菌 (MRSA)的抗菌活性。方法 :琼脂稀释法测定万古霉素和溶葡萄球菌酶对MRSA的最低抑菌浓度 (MIC) ,棋盘法检测 2药联合抑菌作用。结果 :万古霉素对其敏感或低敏MR SA的MIC90 分别为 2mg·L- 1,8mg·L- 1;溶葡萄球菌酶对万古霉素敏感或低敏MRSA的MIC90 分别为 0 .2 5mg·L- 1,0 .5mg·L- 1;2药联合对其敏感株和低敏株的FIC90 (FIC为联合抑菌分数 )较万古霉素单独应用时MIC90 分别减少 4倍和 8倍 ,较溶葡萄球菌酶单独应用时均减少 4倍。FIC指数均小于0 .5。结论 :溶葡萄球菌酶对万古霉素敏感或低敏的MRSA均有良好的体外抗菌活性     

In vitro and in vivo activities of cefpodoxime proxetil against penicillin-resistant Streptococcus pneumoniae

We evaluated in vitro and in vivo activities of cefpodoxime proxetil (CPDX-PR) in comparison with other oral beta-lactams, cefdinir (CFDN), cefditoren pivoxil (CDTR-PI), and faropenem (FRPM), against penicillin-susceptible and -resistant Streptococcus pneumoniae. In vitro activities (MICs) of CPDX, CFDN, CDTR, and FRPM against clinical isolates, penicillin-susceptible S. pneumoniae (PSSP: MIC of penicillin G, < or = 0.063 microgram/ml), penicillin-intermediate S. pneumoniae (PISP: MIC of penicillin G, 0.125-1 microgram/ml), and penicillin-resistant S. pneumoniae (PRSP: MIC of penicillin G, > or = 2 micrograms/ml), were tested by an agar dilution method. The MIC80s of CPDX against 27 PSSP strains, 23 PISP strains, and 23 PRSP strains were 0.032, 1, and 8 micrograms/ml, respectively, which were superior to or equal to those of CFDN (0.063, 4, and 8 micrograms/ml) and were inferior to those of CDTR (0.016, 0.5, and 1 microgram/ml) and FRPM (< or = 0.008, 0.25, and 1 microgram/ml). Infection was induced in mice by inoculating with a PRSP clinical isolate, 9605 or 9601 (serotype 6), or 10692 (serotype 19), through the nares of male ddY mice into the lungs. The mice were treated with drugs with doses of 2-50 mg/kg at 18, 26, 42, and 50 hours after the infection. Viable cell numbers in the lungs and blood were assayed at 66 hours after the infection. The efficacy of each drug was dose-dependent. CPDX-PR showed the most potent in vivo efficacy among the drugs tested against the infections caused by the PRSP strains. MICs of the drugs against PRSP 9605, 9601, and 10692 were as follows: CPDX, 4, 4 and 2 micrograms/ml; CFDN, 16, 16, and 4 micrograms/ml; CDTR, 1, 1, and 0.5 microgram/ml; and FRPM, 1, 0.5, and 0.5 microgram/ml, respectively. Thus, CPDX-PR showed a stronger in vivo activity than that expected from the MICs of CPDX. This was probably caused by the pharmacokinetic advantage of CPDX over the other drugs used in this study.