环丙沙星与其它6种抗菌药物对临床常见致病菌抗菌活性的比较

用琼脂平板稀释法测定了环丙沙星（ＣＰＬＸ）与６种抗菌药物对２１５株临床常见致病的最低抑菌浓度（ＭＩＣ），并统计了敏感率。结果表明７种抗菌药物对大多数受试菌均显示了较高的抗菌活性。ＣＰＬＸ与其他抗菌药物对不同受试菌呈现２．３８％￣１９．０５％的交叉耐药率。该结果提示对其他β－内酰胺类抗菌药物耐药的致病菌引起的严重感染，应根据药敏实验结果慎重选用ＣＰＬＸ。     

Ciprofloxacin in combination with other antimicrobial substances

The antibacterial activity of ciprofloxacin, either alone or in combination with azlocillin, imipenem, mezlocillin or tobramycin, was tested against enterococcus and pseudomonas species. No synergy or antagonism was found by means of the checkerboard titration method used. Subsequently, the bactericidal activity of ciprofloxacin (2 x minimal inhibitory concentration, MIC), azlocillin, imipenem, mezlocillin or tobramycin (2 x MIC) either alone or in combination (1 x MIC each of each substance) was tested against individual strains. No reduction of bactericidal activity in comparison with the effect of the single substances at higher concentration was found, even though the concentrations of each substance were halved. An antagonism is unlikely when ciprofloxacin is combined with one of the beta-lactams studied or with tobramycin. More likely is a slight synergistic effect.     

Activity of moxifloxacin and other quinolones against pneumococci resistant to first-line agents, or with high-level ciprofloxacin resistance

The activity of moxifloxacin and other quinolones was assessed against 288 epidemiologically diverse isolates of Streptococcus pneumoniae, many of them resistant to one or more first-line agents and/or with increased ciprofloxacin resistance (minimum inhibitory concentrations, MICs 16- > 64 mg/l compared with 1-2 mg/l for most isolates). Moxifloxacin and grepafloxacin were the most active quinolone analogues, inhibiting about 90% of the isolates at < or = 1 mg/l, whereas levofloxacin inhibited 64% of isolates at < = 1 mg/l and ciprofloxacin inhibited 42%. Moxifloxacin also was the most active agent against isolates with elevated ciprofloxacin resistance (MIC 16- > 64 mg/l): moxifloxacin MICs of around 4 mg/l were seen for most such isolates, compared with 16-32 mg for levofloxacin and grepafloxacin. The activity of moxifloxacin against pneumococci resistant to one or more first-line agent suggests it will have a useful therapeutic role, although its activity against highly ciprofloxacin resistant isolates seems marginal.     

In vitro activity of beta-lactams in combination with other antimicrobial agents against resistant strains of Pseudomonas aeruginosa

Using the chequerboard titration method, the activity in combination of beta-lactams, fluoroquinolones and aminoglycosides was investigated against 24 Pseudomonas aeruginosa isolates resistant to these antibiotics. Synergy was detected with one or more antimicrobial combinations against 15 of 24 (63%) isolates and partial synergy was detected with one or more combinations against all 24 isolates. No antagonism was seen with any combination. Ceftazidime and cefepime with aztreonam, amikacin and isepamicin showed synergy or partial synergy against 12-20 (50-80%) isolates. Imipenem and meropenem with amikacin and isepamicin showed synergy or partial synergy against eight to 12 (33-50%) isolates. The results of this study indicate that against P. aeruginosa, synergy may occur between beta-lactams, fluoroquinolones and aminoglycosides although the strains are resistant to the individual antibiotics.     

Activity of GAR-936 and other antimicrobial agents against North American isolates of Staphylococcus aureus

The comparative in vitro activity of GAR-936 and 12 other drugs against 602 North American isolates of methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus was determined. The GAR-936 MICs ranged from 0.06 to 1.0 mg/l. The MIC(50)s and MIC(90)s were 0.12 and 0.25 mg/l for MSSA and 0.25 and 0.5 mg/l for MRSA.     

磷霉素与14种抗菌药物分别联用的体外抗菌活性研究

目的研究磷霉素与14种常用抗菌药物分别联用在体外抗耐甲氧西林葡萄球菌(MRS)过程中的相互作用关系，为临床联合用药提供实验依据。方法将磷霉素等15种抗菌药物单独以及磷霉素与14种抗菌药物分别联用作用于163株MRS菌株，通过测定最低抑菌浓度(MIC)、计算部分抑菌浓度(FIC)指数、测定不同作用时间的细菌菌落数、绘制杀菌曲线、扫描电镜观察细菌形态学改变，以评价磷霉素和这些抗菌药物联合应用的体外相互作用关系。结果磷霉素与头孢唑林、头孢呋辛、头孢噻肟、头孢哌酮、头孢甲肟、氧氟沙星、环丙沙星、左氧氟沙星、加替沙星、红霉素、罗红霉素、克拉霉素、庆大霉素、阿米卡星在体外分别联合应用后，MIC值均比单独应用时下降，FIC指数均≤2；联合应用可增强杀菌活性。扫描电镜观察，1／4MIC浓度的阿米卡星或氧氟沙星单独作用于MRS菌时，细菌形态学无改变，1／4MIC浓度的磷霉素单独应用时细菌肿胀、变形，同样浓度两药联用后，细菌发生变形和破坏，细菌数量明显减少。结论磷霉素与14种抗菌药物分别联用对MRS具有协同抗菌作用，尤其能够提高头孢唑林、阿米卡星、氧氟沙星对MRS的杀菌速度。     

Antimicrobial susceptibility surveillance of recent isolates from ophthalmological infections to gatifloxacin and other antimicrobial drugs

The antimicrobial susceptibility of 240 isolates from the ophthalmological infections during July 2003 to March 2004 was determined to gatifloxacin (GFLX), levofloxacin, lomefloxacin and cefmenoxime applicable for ophthalmological infections. The in vitro activities of these drugs against the fresh isolates were compared. The quinolones including GFLX were potently active against Gram-positive bacteria, except for MRSA, a major causative pathogens for ophthalmological infection. When MIC ranges, MIC50 and MIC90 of three quinolones were compared, it was considered that the activity of GFLX was the most active of them. GFLX showed to be more active against opportunistic pathogens including Pseudomonas aeruginosa than other antimicrobial agents, and GFLX was especially potent against Streptococcus pneumoniae and Enterococcus faecalis. In conclusion, GFLX exhibits a potently active against fresh isolates from ophthalmological infections, and has an effective potential in the treatment of ophthalmological infections with the drug to administer eye drops.     

组蛋白去乙酰酶抑制剂联合应用治疗肿瘤的研究进展

组蛋白去乙酰酶(histone deacetylase,HDAC)抑制剂可促进组蛋白乙酰化,调节染色质结构和基因转录。临床前研究,Ⅰ和(或)Ⅱ期临床试验都已证实,HDAC的小分子抑制剂能够有效地促进抑癌基因表达,抑制肿瘤生长并诱导细胞凋亡。在多种肿瘤中都已观察到,HDAC抑制剂与其他抗肿瘤药物联合应用,可在较低的剂量下产生更好的疗效,而不良反应减轻。     

Bile acid sequestrants: their use in combination with other lipid-lowering agents

Several potent drugs are currently available for the treatment of hyperlipidemia. These pharmacotherapies include bile acid sequestrants, HMG-CoA reductase inhibitors (commonly referred to as 'statins'), fibrates and nicotinic acid. Combination therapy to reduce plasma cholesterol levels in hyperlipidemic patients is becoming more popular, as concerns about toxicity resulting from the long-term used of systemically acting drugs are raised. One of the more widespread combinations used to reduce plasma cholesterol levels is that of a bile acid sequestrant and a statin. Combinations of bile acid sequestrants with either niacin or fibrates have been found to be very effective in patients with mixed hyperlipidemia, since the triglyceride-lowering effect of niacin or a fibrate complements the cholesterol-lowering effect of the sequestrant. One major advantage of combination therapy is the ability to reduce the dose of each component to more tolerable levels for the patient. An additional advantage is the reduced cost to achieve the cholesterol reduction goal, as the dose response is relatively good at greatly reduced doses for each component.     

In vitro efficacy of imipenem in combination with six antimicrobial agents against Mycobacterium abscessus

Antimicrobial therapy of Mycobacterium abscessus infection is difficult because there are relatively few effective treatment regimens and single-agent therapy frequently fails clinically. In light of the lack of data on the susceptibility profile of M. abscessus strains recovered from infections in Japan, the in vitro activity of imipenem in combination with clarithromycin, levofloxacin, moxifloxacin, minocycline, amikacin or tobramycin was investigated by the checkerboard method and compared with the combination amikacin and cefoxitin. The combination of imipenem with moxifloxacin, levofloxacin or clarithromycin had a higher synergistic and/or additive effect than amikacin and cefoxitin. A decrease in the MIC(90) value (minimum inhibitory concentration for 90% of the organisms) was observed in the presence of imipenem for clarithromycin, minocycline, levofloxacin and moxifloxacin. The data suggest that a combination regimen including imipenem may be a good choice in empirical treatment of M. abscessus infection.     

加替沙星和环丙沙星对大鼠肝细胞色素P450酶系的影响

目的 研究加替沙星和环丙沙星对大鼠肝微粒体细胞色素P450酶系的影响。方法 加替沙星和环丙沙星400 mg.kg-1灌胃给药大鼠,qd,7天后,用差速离心法制备大鼠肝微粒体,用Lowry法测定蛋白浓度,用分光光度计法检测6种肝微粒体细胞色素P450酶含量及活性,并用单因素方差分析进行统计。结果 加替沙星组的6种细胞色素P450酶的活性与空白对照组相比差异无统计学意义;而环丙沙星能抑制6种细胞色素P450酶中的b5、NADPH-CytC还原酶、氨基比林N-脱甲基酶、红霉素N-脱甲基酶和7-乙氧基香豆素脱烃酶的活性,对CYP450酶系有选择性抑制作用。结论 加替沙星对大鼠肝微粒体CYP450酶系无显著性影响,而环丙沙星对CYP450酶系有选择性抑制作用。     

司帕沙星与其他5种抗菌药体外抗菌活性比较研究

测定了司帕沙星对临床分离的１９９ 株致病菌的体外抗菌活性并与氧氟沙星、环丙沙星、头孢唑啉、头孢噻肟、阿米卡星的抗菌活性进行比较。司帕沙星对革兰阳性菌的ＭＩＣ９０为０．１２５～０．５ｍ ｇ／Ｌ,对金葡球菌、化脓链球菌的抑菌率均为１００％ ,强于氧氟沙星、环丙沙星;对革兰阴性菌也具有良好的体外抗菌活性,与氧氟沙星、环丙沙星相似。不同细菌接种量和不同浓度血清对其抗菌活性无明显影响,仅在ｐＨ５．０ 时抗菌活性略有下降     

国产氟罗沙星体外抗菌活性研究

测定国产氟罗沙星对４９３株临床分离细菌的最低抑菌浓度（ＭＩＣ），并与氧氟沙星、洛美沙星、环丙沙星和几种头孢菌素、氨基糖苷类抗生素作了比较。结果表明：氟罗沙星对革兰氏阴性细菌有强大抗菌活性，对肠杆菌科细菌的ＭＩＣ９０≤１μｇ／ｍｌ。对铜绿假单胞菌亦有较强抗菌活性，其ＭＩＣ５０、ＭＩＣ９０分别为２和４μｇ／ｍｌ。金葡球菌（含ＭＲＳＡ菌株）对氟罗沙星亦很敏感，ＭＩＣ９０≤１μｇ／ｍｌ。链球菌属对其基本耐药，ＭＩＣ９０为８～１６μｇ／ｍｌ。对大多数常见致病菌，氟罗沙星体外抗菌活性与氧氟沙星、洛美沙星相近，稍逊于环丙沙星。对革兰氏阴性菌，氟罗沙星与头孢噻肟、头孢他啶、阿米卡星相当，优于头孢唑林、氨苄西林、哌拉西林、庆大霉素。耐庆大霉素、头孢菌素菌株对氟罗沙星仍敏感。细菌对氟罗沙星单步自发耐药突变频率极低，但通过连续传代培养可以培育出对氟罗沙星高度耐药菌株。     

Anti-tumor effect of honokiol alone and in combination with other anti-cancer agents in breast cancer

Honokiol, an active component isolated and purified from Chinese traditional herb magnolia, was demonstrated to inhibit growth and induce apoptosis of different cancer cell lines such as human leukaemia, colon, and lung cancer cell lines; to attenuate the angiogenic activities of human endothelial cells in vitro; and to efficiently suppress the growth of angiosarcoma in nude mice. In this study, we have demonstrated that treatment of different human breast cancer cell lines with honokiol resulted in a time- and concentration-dependent growth inhibition in both estrogen receptor-positive and -negative breast cancer cell lines, as well as in drug-resistant breast cancer cell lines such as adriamycin-resistant and tamoxifen-resistant cell lines. The inhibition of growth was associated with a G1-phase cell cycle arrest and induction of caspase-dependent apoptosis. The effects of honokiol might be reversely related to the expression level of human epidermal growth receptor 2, (HER-2, also known as erbB2, c-erbB2) since knockdown of her-2 expression by siRNA significantly enhanced the sensitivity of the her-2 over-expressed BT-474 cells to the honokiol-induced apoptosis. Furthermore, inhibition of HER-2 signalling by specific human epidermal growth receptor 1/HER-2 (EGFR/HER-2) kinase inhibitor lapatinib synergistically enhanced the anti-cancer effects of honokiol in her-2 over-expressed breast cancer cells. Finally, we showed that honokiol was able to attenuate the PI3K/Akt/mTOR (Phosphoinositide 3-kinases/Akt/mammalian target of rapamycin) signalling by down-regulation of Akt phosphorylation and upregulation of PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten) expression. Combination of honokiol with the mTOR inhibitor rapamycin presented synergistic effects on induction of apoptosis of breast cancer cells. In conclusion, honokiol, either alone or in combination with other therapeutics, could serve as a new, promising approach for breast cancer treatment.     

In vitro drug interaction studies of atorvastatin with ciprofloxacin, gatifloxacin, and ofloxacin

We describe the in vitro availability of atorvastatin, a potent HMG-CoA reductase inhibitor, in presence of ciprofloxacin, gatifloxacin, and ofloxacin, all with a wide antibacterial spectrum. These studies were performed at 37°C, 48°C, and 60°C in different pH environments, simulating human body compartments. The reactions were studied by UV spectroscopy, and the availability of both the drugs in presence of each other was determined by deriving a simultaneous equation for two component system through modification of Beer’s law. It has been observed that due to interaction, the availability of both atorvastatin and quinolones increased considerably in nearly all pH mediums, which are attributed to the formation of charge-transfer complexes. The results were further confirmed by IR, HNMR, and mass spectrometric studies.     

加替沙星和环丙沙星对大鼠肝微粒体酶系的影响

目的研究加替沙星和环丙沙星对大鼠肝微粒体细胞色素P450酶系的影响.方法Wistar大鼠经加替沙星和环丙沙星400mg/kg灌胃给药,qd×7d后,应用差速离心法制备大鼠肝微粒体,采用Lowry法测定蛋白浓度,应用分光光度计法检测6种肝微粒体细胞色素P450酶含量及活性,并用单因素方差分析进行统计.结果加替沙星组中6种细胞色素P450酶测定结果与空白对照组相比差异无统计学意义,而环丙沙星能抑制6种细胞色素P450酶中的b5、NADPH-CytC还原酶、氨基比林N-脱甲基酶、红霉素N-脱甲基酶和7-乙氧基香豆素脱烃酶的活性,对CYP450酶系有选择性抑制作用.结论加替沙星对大鼠肝微粒体CYP450酶系无显著影响,而环丙沙星对CYP450酶系有选择性抑制作用.     

Treatment of murine pneumonic Francisella tularensis infection with gatifloxacin, moxifloxacin or ciprofloxacin

The efficacies of gatifloxacin and moxifloxacin were assessed in a BALB/c mouse model of pneumonic tularemia and compared with the efficacy of ciprofloxacin. The rate of relapse following dexamethasone treatment was also investigated. Mice were given 100 mg/kg of the antibiotic by oral administration twice daily for 14 days following an aerosol challenge. All three fluoroquinolones prevented disease during the treatment period, but significant failure rates occurred after the cessation of therapy. Both gatifloxacin and moxifloxacin were more effective than ciprofloxacin at reducing late mortality. Fluoroquinolones may therefore be considered useful candidates for the treatment of pneumonic tularemia.     

Evaluation of dalbavancin in combination with nine antimicrobial agents to detect enhanced or antagonistic interactions

Dalbavancin is a potent, once-weekly administered lipoglycopeptide that is active against a broad spectrum of Gram-positive species. Synergy studies were performed with dalbavancin and each of nine antimicrobial agents (90 tests in total) representing nine antimicrobial classes using the broth microdilution checkerboard method to establish in vitro interactive categories. Antagonism was not observed between dalbavancin and any of the antimicrobials tested. However, dalbavancin was synergistic or partially synergistic with oxacillin for staphylococci, including methicillin-resistant strains, vancomycin-intermediate Staphylococcus aureus and enterococci, a significant finding that warrants further investigation to establish its potential clinical relevance.