替考拉宁对葡萄球菌的体外抗菌活性研究

目的 :测定替考拉宁对葡萄球菌的体外抗菌活性。方法 :采用琼脂二倍稀释法测定替考拉宁对 492株葡萄球菌的最低抑菌浓度 (MIC) ,其中金黄色葡萄球菌 3 2 4株 ,表皮葡萄球菌 1 68株。结果 :替考拉宁对葡萄球菌的MIC90 值均为 1mg·L-1,明显低于氧氟沙星、红霉素和苯唑西林 ,与万古霉素相当 ;替考拉宁对甲氧西林耐药金黄色葡萄球菌 (MR SA)和对甲氧西林耐药表皮葡萄球菌 (MRSE)的MIC90 分别为 4mg·L-1和 2mg·L-1,是万古霉素的1 / 2。抗菌活性明显高于氧氟沙星和红霉素。结论 :替考拉宁对葡萄球菌的体外抗菌活性是万古霉素的 2倍 ,明显强于氧氟沙星和红霉素     

用蒙特卡洛模拟优化耐甲氧西林金黄色葡萄球菌感染的肾功能不全低龄患儿万古霉素的给药方案

目的 应用蒙特卡洛模拟评价万古霉素在肾功能正常与不全低龄耐甲氧西林金黄色葡萄球菌(MRSA)感染患儿中的给药方案.方法 收集2013—2014年成都地区万古霉素对MRSA菌株的最低抑菌浓度值(MIC)和其在2个月 ～2岁中国低龄患儿中药动学资料,经Crystal Ball软件模拟5000例次得到相应目标获得概率(PTA)与累计反应分数(CFR).结果 万古霉素对MRSA的MIC分布频率,MIC为0.03、0.06、0.12、0.25、0.50 mg·L-1时各占12.79％,MIC为1、2 mg·L-1时各占29.07％ 、6.98％.万古霉素达满意抗菌活性的最低剂量:肾功能正常者(A组),MIC为0.03～0.06、0.12和0.25 mg·L-1时分别予30、37.5和80 mg·kg-1·d-1,MIC为0.5～2 mg·L-1时即使80 mg·kg-1·d-1也不能达满意抗菌活性;肾功能轻度不全者[B组,估算的肾小球滤过率(eGFR)为60～89 mL·min-1·1.73 m-2],MIC为0.03～0.12、0.25和0.5 mg·L-1时分别予30、40和80 mg·kg-1·d-1,MIC为1～2 mg·L-1时即使80 mg·kg-1·d-1也不能达满意抗菌活性;肾功能中度不全者(C组,eGFR为30～59 mL·min-1·1.73 m-2),MIC为0.03～0.25、0.5 mg·L-1时分别予30、50 mg·kg-1·d-1,MIC为1～2 mg·L-1时即使80 mg·kg-1·d-1也不能达满意抗菌活性.各方案下A、B组对MRSA的CFR均<90％.结论 感染MR-SA的肾功能正常与轻度不全低龄患儿经验性应用万古霉素时可考虑联合用药,结合各MIC分布频率和达满意抗菌活性的最低剂量可知,大多数肾功能正常低龄患儿按40 mg·kg-1·d-1给药剂量偏低,绝大多数肾功能中度不全者应用50～80 mg·kg-1·d-1可获得满意抗菌活性.     

头孢硫脒与其他6种抗菌药物对表皮葡萄球菌体外联合药敏的研究

目的 :评价头孢硫脒分别与万古霉素、奈替米星、阿米卡星、环丙沙星、左氧沙星和加替沙星等 6种抗菌药物联合用药 ,对于表皮葡萄球菌 (Staphylo coccusepidermidis ,SE)的体外联合抗菌效应。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 6组抗菌药物对 30株临床分离的表皮葡萄球菌的最低抑菌浓度 (MIC) ,并计算部分抑菌指数 (FIC指数 )。结果 :头孢硫脒对表皮葡萄球菌的MIC50 、MIC90 为 1、6 4mg·L-1;与万古霉素、奈替米星、阿米卡星、环丙沙星、左氧沙星、加替沙星联合应用后 ,其MIC50 分别降低至 0 .12 5、0 .12 5、0 .12 5、0 .12 5、0 .2 5、0 .12 5mg·L-1,MIC90 分别降低至 1、1、1、2、1、1mg·L-1。结论 :6种抗菌药物与头孢硫脒联合用药后 ,对表皮葡萄球菌球菌基本表现为协同或相加作用 ,并以协同作用为主 ,无关作用较少 ,无拮抗作用。     

莫匹罗星与4种常用抗菌药物体外抗菌活性比较

目的 :莫匹罗星与 4种常用抗菌药物体外抗菌活性的比较。方法 :1 1 5株临床分离菌株 ,采用琼脂稀释法对莫匹罗星、环丙沙星、阿米卡星、青霉素、红霉素分别进行最小抑菌浓度 (MIC)测定。结果 :90株革兰阳性菌的MIC50 分别为 1 ,0 .2 5 ,1 ,8,1 2 8mg·L-1。莫匹罗星对葡萄球菌和链球菌的MIC50 分别为 0 .5 ,0 .2 5mg·L-1。对大肠埃希菌的MIC50 为 >64mg·L-1。结论 :莫匹罗星对革兰阳性菌有较强的抗菌活性 ,尤其对葡萄球菌和链球菌高度敏感 ,甚至对耐甲氧西林葡萄球菌 (MRSA)抗菌效果也好。莫匹罗星总的抗菌活性与环丙沙星、阿米卡星相似 ,明显优于青霉素、红霉素 ,并与其他抗生素无交叉耐药性。     

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。     

莫西沙星对224株凝固酶阴性葡萄球菌的体外抗菌活性观察

目的观察莫西沙星对224株表皮葡萄球菌、溶血葡萄球菌和里昂葡萄球菌等凝固酶阴性葡萄球菌（CNS）的体外抗菌活性。方法用二倍琼脂稀释法测定其最低抑菌浓度（MIC）。结果莫西沙星对表皮葡萄球菌、溶血葡萄球菌等CNS的抑菌效果较好，对124株表皮葡萄球菌的MIC50和MIC90分别为≥0．063和0．25μg／ml；对42株溶血葡萄球菌和14株里昂葡萄球菌的MIC90分别为2和0．5μg／ml。结论莫西沙星对表皮葡萄球菌、溶血葡萄球菌、里昂葡萄球菌和人葡萄球菌的抗菌效果好，敏感率分别为96．77％、85．71％、100％和100％；对35株耳葡萄球菌等的敏感率为100％。     

国产头孢硫脒对224株凝固酶阴性葡萄球菌的体外抗菌活性研究

目的观察头孢硫脒对表皮葡萄球菌、溶血葡萄球菌等凝固酶阴性葡萄球菌的体外抗菌活性。方法采用琼脂稀释法对头孢硫脒进行224株表皮葡萄球菌、溶血葡萄球菌等凝固酶阴性葡萄球菌的最低抑菌浓度(MIC)测定。结果头孢硫脒对100株耐甲氧西林的凝固酶阴性葡萄球菌和124株甲氧西林敏感的凝固酶阴性葡萄球菌的MIC50,MIC90分别为0．5、128、≤0．125和2μg／ml。对甲氧西林敏感的表皮葡萄球菌(MSSE)、溶血葡萄球菌(MSSH)和里昂葡萄球菌(MSSL)的MIC90分别为0．5、2．0和2．0μg／ml。结论头孢硫脒对124株甲氧西林敏感的凝固酶阴性葡萄球菌具有较强的抑菌力。     

乳酸左氧氟沙星体外抗菌作用的研究

目的 :研究乳酸左氧氟沙星的体外抗菌活性。方法 :采用两倍稀释法对临床分离的 8种细菌进行体外抗菌试验。结果 :该药对金黄色葡萄球菌、肺炎链球菌甚为敏感 ,其MIC50 为 0 0 5mg·L-1,MIC90 为 0 2 0mg·L-1,MBC50 为 0 0 5mg·L-1,MBC90 为 0 39mg·L-1。结论 :乳酸左氧氟沙星比氧氟沙星的抗菌活性强     

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.     

五倍子提取物对100株溶血葡萄球菌等凝固酶阴性葡萄球菌的体外抗菌活性观察

目的观察五倍子提取物对溶血葡萄球菌等凝固酶阴性葡萄球菌的体外抗菌活性。方法采用新的中药抑菌实验方法对五倍子提取物进行100株溶血葡萄球菌等凝固酶阴性葡萄球菌的最低抑菌浓度MIC测定。结果五倍子提取物对57株耐甲氧西林的凝固酶阴性葡萄球菌和43株甲氧西林敏感的凝固酶阴性葡萄球菌的MIC50、MIC90分别为0.072、0.072和0.288、0.144mg/ml。结论五倍子提取物对100株凝固酶阴性葡萄球菌具有较强的抑菌力,说明五倍子是极具开发前景的抗感染中药。     

Antimicrobial susceptibility of Gram-positive bacterial isolates from the Asia-Pacific region and an in vitro evaluation of the bactericidal activity of daptomycin, vancomycin, and teicoplanin: a SENTRY Program Report (2003-2004)

Medical centres in eight countries in the Asia-Pacific region provided 2391 isolates for the SENTRY Antimicrobial Surveillance Program during 2003-2004 to determine their susceptibility to several antimicrobial classes, including daptomycin. Daptomycin, vancomycin and teicoplanin minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined for 120 isolates of Staphylococcus aureus, which included wild-type (WT) methicillin-resistant S. aureus (MRSA) and strains with decreased susceptibility to vancomycin (hetero-vancomycin-intermediate S. aureus (hVISA)). Oxacillin-resistant staphylococcal isolates were much less susceptible to the other tested agents compared with oxacillin-susceptible strains. Vancomycin resistance was higher among Enterococcus faecium (10.3%) than Enterococcus faecalis (0.4%), and macrolide resistance was high both for beta-haemolytic (17.7%) and viridans group (48.7%) streptococci. Daptomycin (MIC for 90% of the organisms (MIC(90))=0.5-1mg/L) was two-fold more potent than vancomycin, with >99% susceptibility when tested against staphylococci. All tested isolates of E. faecalis (MIC(90)=2mg/L) and beta-haemolytic streptococci (MIC(90)=0.5mg/L) were susceptible to daptomycin. Daptomycin MIC and MBC values were slightly higher for the hVISA isolates compared with WT-MRSA, with MBC/MIC ratios of only 1-2 for both groups. The MBC/MIC ratio for vancomycin was often greater when tested against these strains, particularly hVISA. In contrast, teicoplanin MBC/MIC ratios were significantly higher, with many of the strains showing values consistent with tolerance (>or=32). Daptomycin was demonstrated to have excellent in vitro activity when tested against Gram-positive isolates collected from Asia-Pacific countries, including hVISA strains.     

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。     

In vitro evaluation of ceftaroline alone and in combination with tobramycin against hospital-acquired meticillin-resistant Staphylococcus aureus (HA-MRSA) isolates

The aim of this study was to evaluate the in vitro activity of ceftaroline and its potential for synergy with tobramycin in comparison with vancomycin against a collection of hospital-acquired meticillin-resistant Staphylococcus aureus (HA-MRSA), including isolates with reduced susceptibility to glycopeptides. Ceftaroline, vancomycin, daptomycin and linezolid susceptibilities were determined for 200 HA-MRSA isolates. Four randomly selected strains [including one vancomycin-intermediate S. aureus (VISA) and one heteroresistant VISA (hVISA)] were evaluated in time–kill experiments with ceftaroline and vancomycin alone or combined with tobramycin at 0.25 and 0.5 times the minimum inhibitory concentration (MIC). MICs for 50% and 90% of the organisms (MIC₅₀ and MIC₉₀, respectively) were both 1 mg/L for ceftaroline and were 1 mg/L and 2 mg/L, respectively, for vancomycin. The same ceftaroline MIC ranges (0.25–2 mg/L) were observed for isolates recovered from respiratory tract samples, blood or skin. In time–kill experiments, no synergy was observed at 0.25× MIC against any tested isolates with either ceftaroline or vancomycin. In contrast, the combination of ceftaroline plus tobramycin at 0.5× MIC was synergistic against the two MRSA strains and the hVISA but was indifferent against the VISA isolate. In conclusion, ceftaroline demonstrated antimicrobial activity independently of the specimen source and exhibited lower MICs than vancomycin. Finally, at sub-MIC levels, ceftaroline plus tobramycin displayed significantly greater activity than vancomycin plus tobramycin against MRSA (P < 0.01).     

Nationwide sensitivity surveillance of various antibiotic activities against bacteria isolated from patients with severe infections]

The susceptibility of 3,058 bacterial strains isolated between January and March, 1997 from patients with severe infections in Japan to ciprofloxacin and other injectable antimicrobial agents was measured using broth microdilution method. Methicillin-resistant Staphylococcus aureus (MRSA) strains were generally sensitive to vancomycin, teicoplanin and arbekacin, and resistant to CPFX and other antibacterial agents. MIC90 of CPFX against Streptococcus pneumoniae, to which MIC of ampicillin was more than 4 micrograms/mL, was below 2 micrograms/mL. PRSP (Penicillin resistant S. pneumoniae), which was also resistant to cephalosporins and carbapenems, showed no cross-resistance to CPFX. The susceptibility of Gram-negative bacteria to CPFX was as high as that to carbapenems. Especially, MIC90 against Pseudomonas aeruginosa was 2 micrograms/mL. 3 strains of isolated 446 P. aeruginosa strains had blaIMP gene. CPFX and pazufloxacin demonstrated good susceptibility with 0.25 microgram/mL of MIC to 2 strains of these 3 strains. The susceptibility rate of the most common isolates from patients suffering from lower respiratory tract infections excluding MRSA to CPFX was more than 80% (indication: % strains < pneumonia break point).     

In vivo efficacy of the antimicrobial peptide ranalexin in combination with the endopeptidase lysostaphin against wound and systemic meticillin-resistant Staphylococcus aureus (MRSA) infections

New treatments are urgently required for infections caused by meticillin-resistant Staphylococcus aureus (MRSA) as these strains are often resistant to multiple conventional antibiotics. Earlier studies showed that ranalexin, an antimicrobial peptide (AMP), in combination with lysostaphin, an antistaphylococcal endopeptidase, synergistically inhibits the growth of MRSA, meaning that it deserved consideration as a new anti-S. aureus therapy. Using haemolysis and Vero cell viability assays, ranalexin with lysostaphin is proven to be non-toxic at antibacterial concentrations. In human serum, ranalexin with lysostaphin is significantly more effective against MRSA than treatment with either component alone. In a rabbit model of wound infection, ranalexin with lysostaphin reduced MRSA in the wound by ca. 3.5 log₁₀ colony-forming units (CFU) compared with the untreated control. The combination is significantly more effective than treatment with ranalexin or lysostaphin alone. In a mouse model of systemic infection, ranalexin with lysostaphin reduced MRSA kidney burden by ca. 1 log₁₀ CFU/g compared with untreated controls or treatment with ranalexin or lysostaphin alone. Importantly, the combination is synergistically bactericidal against various S. aureus isolates in vitro, including those with reduced susceptibility to lysostaphin or vancomycin. Ranalexin and lysostaphin could be incorporated in wound dressings for the prevention and treatment of topical S. aureus infections. That AMPs can enhance the antibacterial effectiveness of lysostaphin in vivo highlights a new avenue of research in the fight against drug-resistant staphylococci.     

Synergistic action of cefodizime and other antimicrobial agents on clinically isolated microorganisms. I. Synergistic action with minocycline]

Since cefodizime (CDZM) shows a broad antimicrobial spectrum and relatively long half life in blood, we examined its synergistic action with minocycline (MINO) in vitro against Staphylococcus aureus. 1. CDZM in the presence of MINO, most of cases 1 MIC showed FIC index greater than 0.5-less than or equal to 2 against methicillin-susceptible S. aureus (MSSA), thus the results suggested a synergistic action against S. aureus. 2. CDZM in combination with MINO at 1 MIC or sub MIC where therapeutically a favorable efficacy is expected on MINO-susceptible strains exhibited FIC index less than or equal to 0.5-less than or equal to 1, Methicillin-resistant S. aureus (MRSA), thus suggesting a synergistic action against MINO-susceptible MRSA strains. Synergism was hardly recognized against MINO-resistant MRSA strains, however. 3. Synergism by both drugs was produced in MINO-susceptible strains of S. aureus including MRSA where MIC by CDZM was high or moderate, but no synergism was demonstrated against MINO-resistant strains. That is, synergistic action by both drugs was thought to depend on antimicrobial activity of MINO.     

抗菌药物联用对耐甲氧西林金黄色葡萄球菌体外抗菌活性研究

目的了解万古霉素与头孢哌酮/舒巴坦、亚胺培南、左氧氟沙星联用对MRSA的体外抗菌活性,指导临床合理用药。方法常规方法培养分离细菌,用VITEK微生物自动分析仪或API系统鉴定到种。MRSA鉴定应用乳胶凝集试剂盒,药敏试验采用肉汤倍比稀释法和琼脂平板稀释法。结果万古霉素对40株MRSA的MIC90为4mg/L,而与头孢哌酮/舒巴坦、亚胺培南、左氧氟沙星联用MIC90降为0.25～1mg/L。结论万古霉素与上述三种药物联用以协同作用为主,抗菌活性提高4倍以上。临床上治疗由MRSA引起的重症感染应根据药敏试验结果采用万古霉素与亚胺培南或头孢哌酮/舒巴坦或其它抗菌药物联合应用。