In vitro activity of moxifloxacin,levofloxacin, gatifloxacin and linezolid against Mycobacterium tuberculosis

The in vitro activity of moxifloxacin, gatifloxacin, levofloxacin and linezolid was evaluated against 234 strains of Mycobacterium tuberculosis isolated in the Southeast of Spain. All drugs tested showed good activity, with an MIC₉₀ of less than 1 mg/l, and were active against isociacide and rifampicin resistant strains. Three strains were resistant to isoniazid and to the fluoroquinolones, which suggested the existence of mechanisms of resistance not yet described. These new compounds may prove to be therapeutic alternatives for treatment of multi-resistant tuberculosis and further studies should be done to demonstrate their true usefulness.     

Comparative in vitro bacteriostatic and bactericidal activity of trovafloxacin, levofloxacin and moxifloxacin against clinical and environmental isolates of Legionella spp.

The susceptibility of 140 Legionella spp isolates (106 clinical and 34 environmental isolates) to trovafloxacin (TRFX), levofloxacin (LEVX), moxifloxacin (MOFX), ciprofloxacin (CIPX), ofloxacin (OFLX), erythromycin (ERY), azithromycin (AZI) and rifampicin (RIF) was studied using a standard microdilution method and buffered yeast extract broth (BYE) supplemented with 0.1% alpha-ketoglutarate. The post-antibiotic effects (PAEs) of the study drugs against 10 clinical isolates of Legionella pneumophila sg.1 were compared. The MIC inhibiting 90% of strains tested on BYEalpha broth were 0.008, 0.016, 0.016, 0.06, 0.125, 0.5, 0.5, and 0.004 mg/l for TRFX, LEVX, MOXX, CIP, OFLX, ERY, AZI, and RIF, respectively. The MBC/MIC ratios ranged from one to eight depending on the antibiotic tested: TRFX [1x-2 x MIC], LEVX, MOFX, CIPX and OFLX [1x-4 x MIC], RIF [2x-4 x MIC], ERY and AZI [2x-8 x MIC]. TRFX, RIF, LEVX, MOFX, CIPX, OFLX, ERY and AZI showed similar activity against Legionella species other than L. pneumophila. One-hour exposures to the study antimicrobial agents at a concentration of 4 x MIC resulted in PAEs as follows (average in hours): TRFX: 2.68 h; RIF: 2.63 h; CIPX: 2.62 h; MOFX: 2.56 h; LEVX: 2.41 h; OFLX: 2.25 h; AZI: 1.65 h; and ERY: 1.54 h. In conclusion, our in vitro data confirm that trovafloxacin, levofloxacin, moxifloxacin and rifampicin have excellent bacteriostatic and bactericidal activity against Legionella spp and show significant post-antibiotic effect.     

In vitro activity of gatifloxacin compared with gemifloxacin, moxifloxacin, trovafloxacin, ciprofloxacin and ofloxacin against uropathogens cultured from patients with complicated urinary tract infections

Minimum inhibitory concentrations (MICs) of gatifloxacin were compared with those of gemifloxacin, moxifloxacin, trovafloxacin, ciprofloxacin and ofloxacin using an agar dilution method for 400 uropathogens cultured from the urine of urological patients with complicated and/or hospital-acquired urinary tract infections (UTI). The collection of strains was made up of Enterobacteriaceae (34.5%), enterococci (31.5%), staphylococci (21.2%) and non-fermenting bacteria (12.8%). The antibacterial activity of the three newer fluoroquinolones, gatifloxacin, gemifloxacin, and moxifloxacin, were similar, but showed some drug specific differences. Gemifloxacin was most active against Escherichia coli, but less so against Proteus mirabilis. In this series all isolates of E. coli were inhibited at a MIC of 0.25 mg/l gatifloxacin and moxifloxacin and by 0.125 mg/l gemifloxacin. The MIC distribution of all fluoroquinolones showed a bimodal distribution for staphylococci, enterococci and Pseudomonas aeruginosa. The two modes for P. aeruginosa were 1 and 64 mg/l for gemifloxacin and moxifloxacin and 0.5 and 64 mg/l for gatifloxacin. For staphylococci the two modes were 0.125 and 2 mg/l for gatifloxacin, 0.03 and 4 mg/l for gemifloxacin, and 0.03 and 2 mg/l for moxifloxacin; for enterococci, 0.25 and 16 mg/l for gatifloxacin, 0.06 and 2 mg/l for gemifloxacin, and 0.25 and 8 mg/l for moxifloxacin. Compared with trovafloxacin the MICs were similar, but the newer fluoroquinolones were more active than ciprofloxacin and ofloxacin against Gram-positive bacteria. Of the newer fluoroquinolones gatifloxacin had the highest rate of renal excretion and could be considered a promising alternative fluoroquinolone agent for the treatment of UTI.     

Comparative in vitro and in vivo antimicrobial activities of sitafloxacin, gatifloxacin and moxifloxacin against Mycobacterium avium

Moxifloxacin exhibits therapeutic activity against Mycobacterium avium infection in mice. Since not only moxifloxacin but also another 8-methoxy quinolone, gatifloxacin, and a C-8-chloro quinolone, sitafloxacin, show favourable antimycobacterial activity in vitro, their anti-M. avium activities were compared in vivo. Minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs) and mutant prevention concentrations (MPCs) of the test quinolones for M. avium were determined by microdilution in 7HSF broth. Antimicrobial activity against intracellular bacteria was measured using Mono Mac 6 human macrophages. Therapeutic efficacy of the quinolones when administered subcutaneously with or without clarithromycin plus ethambutol was assessed using mice intravenously infected with M. avium in terms of changes in bacterial loads in the lungs and spleen following infection. Based on the MICs, MBCs and MPCs, the in vitro activities of sitafloxacin and moxifloxacin were greater than that of gatifloxacin. Moxifloxacin exhibited the strongest activity against intramacrophage M. avium. When each test quinolone was administered alone to infected mice, sitafloxacin and gatifloxacin exhibited greater therapeutic efficacy than moxifloxacin based on intrapulmonary bacterial elimination. However, moxifloxacin exerted greater activity in killing bacteria in the spleen. Moxifloxacin and sitafloxacin exhibited combined effects on intrapulmonary bacterial elimination when administered to mice in combination with clarithromycin plus ethambutol. Sitafloxacin exerted the most marked combined effects in bacterial killing in the spleen. Levofloxacin displayed the lowest in vitro and in vivo activities amongst the tested quinolones. Taken together, these findings indicate that sitafloxacin and moxifloxacin exhibit favourable activities against M. avium in vitro and in vivo.     

Global in vitro activity of tigecycline and linezolid against Gram-positive organisms collected between 2004 and 2009

This study reports the antimicrobial activity of tigecycline and comparator antimicrobials, including linezolid, against Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis and Enterococcus faecium collected as part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) between 2004 and 2009. Minimum inhibitory concentrations (MICs) were determined using broth microdilution methodology according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). Antimicrobial susceptibility was determined according to CLSI criteria. For tigecycline, the US Food and Drug Administration (FDA)-approved criteria were used. Overall, 41.3% (8249/19 982) of S. aureus collected were meticillin-resistant S. aureus (MRSA). All MRSA were susceptible to linezolid and 99.98% were susceptible to tigecycline. A total of 2.3% of E. faecalis (201/8576) and 39.7% of E. faecium (1226/3088) were vancomycin-resistant. Linezolid and tigecycline MIC(90) values (MIC at which 90% of isolates inhibited) against the Enterococcus spp. were 2mg/L and ≤ 0.25 mg/L, respectively. All S. pneumoniae [including 6.2% (599/9618) penicillin-non-susceptible] were susceptible to linezolid and vancomycin; tigecycline MIC(90) values were ≤ 0.12 mg/L. This report demonstrates the continuing good activity of tigecycline and linezolid against Gram-positive isolates globally, including resistant organisms such as MRSA, vancomycin-resistant enterococci and penicillin-resistant S. pneumoniae, with antimicrobial activity maintained over the 6 years of isolate collection.     

Comparative in vitro activity of tigecycline and other antimicrobials against Gram-negative and Gram-positive organisms collected from the Asia-Pacific Rim as part of the Tigecycline Evaluation and Surveillance Trial (TEST)

As part of the Tigecycline Evaluation and Surveillance Trial (TEST), Gram-negative and Gram-positive organisms were collected from 31 medical centres in nine countries in the Asia-Pacific Rim between 2004 and 2007. Overall, 34.2% of Acinetobacter spp. were multidrug-resistant, and 17.0% of Klebsiella pneumoniae and 10.6% of Escherichia coli produced extended-spectrum beta-lactamases. A total of 39.5% of Staphylococcus aureus were meticillin-resistant and 21.7% of Enterococcus faecium were vancomycin-resistant. Tigecycline MIC(90) values (minimum inhibitory concentration for 90% of the organisms) were 相似文献   

Antibacterial activity of high concentrations of carvedilol against Gram-positive and Gram-negative bacteria

Many drugs used to treat non-infectious diseases have also shown excellent antibacterial activity or the ability to enhance the action of antibiotics. The aim of this study was to investigate the antibacterial activity of a popular β-blocker, carvedilol, and its mechanism of antibacterial action. The antibacterial activity of carvedilol was evaluated using the microdilution method and its influence on the viability of bacterial cells was investigated by the alamarBlue^® test. Changes in phospholipid and fatty acid composition were analysed using LC-MS/MS and GC-MS techniques. The permeability of bacterial cell membranes following exposure to carvedilol was studied using propidium iodide staining and confocal microscopy. The ability of the tested bacteria to degrade carvedilol was examined by LC-MS/MS. In this study, the antibacterial activity of carvedilol is described for the first time, with a decrease in the viability of all assayed bacteria observed following treatment with the β-blocker. Staphylococcus aureus and Staphylococcus epidermidis were found to be the most sensitive among the tested strains. Significant modifications to fatty acid composition were observed in S. aureus incubated with carvedilol. Moreover, the cell membrane permeability of bacteria incubated with carvedilol was higher for Gram-positive bacteria than for Gram-negative bacteria. Furthermore, Gram-negative Escherichia coli and Pseudomonas aeruginosa strains, which were highly resistant to carvedilol, exhibited an ability to eliminate carvedilol from the growth medium. In addition, three carvedilol metabolites were identified in E. coli and P. aeruginosa cultures. The antibacterial activity of carvedilol may suggest its potential usefulness in the synthesis of new antibacterial drugs.     

Single and multi-step resistance selection study in Streptococcus pneumoniae comparing ceftriaxone with levofloxacin,gatifloxacin and moxifloxacin

Attempts were made to select resistant pneumococcal mutants by sequential subculturing of 12 clinically isolated pneumococci, [four were penicillin sensitive (MIC) 0.03-0.06 mg/l, four penicillin intermediate (MIC 0.25-0.5 mg/l) and four penicillin resistant (MIC 2-4 mg/l)] in sub-inhibitory concentrations of ceftriaxone, levofloxacin, gatifloxacin and moxifloxacin. Subculturing in gatifloxacin, levofloxacin, moxifloxacin and ceftriaxone selected 12 mutants (12/12), 10 mutants (10/12), 10 mutants (10/12) and three mutants (3/12), respectively. DNA sequencing of the quinolone-resistant mutants showed that most strains had mutations in GyrA at E85 or S81. This in vitro mutation study demonstrates a clear distinction between the low frequency of development of resistance with ceftriaxone exposure as opposed to the high frequency with quinolone exposure.     

Correlation between in vitro and in vivo activity of levofloxacin and moxifloxacin against pneumococcal strains with different susceptibilities to fluoroquinolones

In vitro and in vivo models were developed to evaluate the efficacy of levofloxacin and moxifloxacin against three serotype 3 pneumococcal strains with different susceptibilities to fluoroquinolones (wild-type, parC mutant, and parC, parE and gyrA mutant). Levofloxacin and moxifloxacin reduced the bacterial burden in the in vitro pharmacodynamic and animal models for the wild-type strain but had very little activity against the fully resistant strain (parC, parE and gyrA mutant). Levofloxacin showed very little activity both in the in vitro pharmacodynamic model and in the animal model for the strain having a mutation in parC (levofloxacin and moxifloxacin minimum inhibitory concentrations, 2mg/L and 0.25mg/L, respectively). However, moxifloxacin still had a significant in vitro and in vivo activity against this strain.     

某院革兰阴性杆菌对美罗培南与亚胺培南体外敏感性比较

目的:比较美罗培南和亚胺培南对687株临床分离的革兰阴性杆菌体外抗菌活性,为抗感染治疗的药物选择提供参考。方法:采用MIC法测定同一株革兰阴性菌对亚胺培南和美罗培南的敏感性,对细菌的耐药结果进行统计学分析。结果:150株大肠埃希菌、245株肺炎克雷伯菌和137株鲍曼不动杆菌对亚胺培南、美罗培南的敏感菌株之比是146:147、233:232和24:22,经χ²检验 P>0.05,两药敏感性差异无统计学意义;但铜绿假单胞菌对美罗培南的敏感率高于亚胺培南(P<0.05),鲍曼不动杆菌对亚胺培南、美罗培南的敏感率均小于20%。结论:亚胺培南和美罗培南对肠杆菌科仍保持高活性有同样有效,对于铜绿假单胞菌引起的严重感染,美罗培南体外试验有着较高抗菌活性。亚胺培南和美罗培南对鲍氏不动杆菌疗效不佳。     

Antibacterial activity and interactions of plant essential oil combinations against Gram-positive and Gram-negative bacteria

The aim of this study was to compare the antibacterial effects of several essential oils (EOs) alone and in combination against different Gram-positive and Gram-negative bacteria associated with food products. Parsley, lovage, basil, and thyme EOs, as well as their mixtures (1:1, v/v), were tested against Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Salmonella typhimurium. The inhibitory effects ranged from strong (thyme EO against E. coli) to no inhibition (parsley EO against P. aeruginosa). Thyme EO exhibited strong (against E. coli), moderate (against S. typhimurium and B. cereus), or mild inhibitory effects (against P. aeruginosa and S. aureus), and basil EO showed mild (against E. coli and B. cereus) or no inhibitory effects (against S. typhimurium, P. aeruginosa, and S. aureus). Parsley and lovage EOs revealed no inhibitory effects against all tested strains. Combinations of lovage/thyme and basil/thyme EOs displayed antagonistic effects against all bacteria, parsley/thyme EOs against B. cereus, S. aureus, P. aeruginosa, and E. coli, and lovage/basil EOs against B. cereus and E. coli. Combinations of parsley/lovage and parsley/basil EOs exhibited indifferent effects against all bacteria. The combination of lovage/basil EO showed indifferent effect against S. aureus, P. aeruginosa, and S. typhimurium, and the combination parsley/thyme EO against S. typhimurium. Thyme EO has the highest percentage yield and antibacterial potential from all tested formulations; its combination with parsley, lovage, and basil EOs determines a reduction of its antibacterial activity. Hence, it is recommended to be used alone as the antibacterial agent.     

Comparative in vitro activity of nine antistaphylococcal agents against 275 recent isolates of Gram-positive cocci

The aim of this study was to compare the in vitro activities of 9 antistaphylococcal agents including teicoplanin (TEI) against 275 non-repetitive clinical strains representing 15 species of staphylococci and 27 strains of Enterococcus (E.) faecalis, isolated from various specimens between 1991-1992 at a Canadian teaching hospital. The NCCLS agar dilution method was used (10(4) colonyforming units/spot). In terms of MIC(90), TEI and vancomycin (VAN) appeared to be the most potent antibiotics against all staphylococci tested (TEI: 2.0-4.0 mug/ml; VAN: 1.0-2.0 mug/ml; ciprofloxacin (CPF): 0.25-32 mug/ml; cefazolin (CEF): 8.0-256 mug/ml; methicillin (MET): 2.0->256 mug/ml; imipenem (IMP): 1.0-32 mug/ml; erythromycin (ERT): 16->256 mug/ml; ampicillin (AMP): 16-128 mug/ml; fusidic acid (FSA): 0.5-16 mug/ml). Multiple resistant strains, including MET-resistant Staphylococcus (Staph.) aureus and Staph. epidermidis, were susceptible to TEI and VAN with respective MICs of 2-4 mug/ml and 1-2 mug/ml regardless of specimen type. Moreover, TEI was highly active against E. faecalis (MIC(90) for TEI and VAN: 0.5 and 4.0 mug/ml, respectively).     

头孢硫脒等抗菌药物对革兰氏阳性球菌体外抗菌活性研究

目的 评价头孢硫脒及其他12种抗菌药对革兰氏阳性球菌的体外抗菌活性。方法 从本院2001年9月～12月临床病人血液、痰、分泌物、尿标本中分离出57株致病菌，经VITEK—AMS分析仪鉴定，共有金葡球菌24株，凝固酶阴性葡萄菌21株，粪肠球菌12株。质控金葡球菌ATCC25923，粪肠球菌ATCC29212。判断标准按2000年NCCLS标准。结果 头孢硫脒等10种抗菌药对金葡球菌体外抗菌活性，头孢硫脒敏感率87．5％，有2株耐药菌(8．33％)，敏感率与万古霉素、利福平比较无统计意义(P＞0．05)。头孢硫脒等10种抗菌药对凝固酶阴性葡萄球菌体外抗菌活性，头孢硫脒敏感率85．7％，有3株耐药菌株(14．29％)，敏感率略低于万古霉素、利福平(P＞0．05)，显著高于庆大霉素、氧氛沙星等(P＜0．05)。对粪肠球菌，头孢硫脒敏感率83．33％，有2株耐药菌株(16．67％)，其敏感率与庆大霉素、四环素、链霉素差异显著(P＜0．005，P＜0．01)。结论头孢硫脒是临床治疗金葡球菌、凝固酶阴性葡萄球菌、粪肠球菌感染的有效药物。     

加替沙星对金黄色葡萄球菌的体外抗菌活性

考察加替沙星对金黄色葡萄球菌的体外抗菌活性以及抗MRSA的能力。采用药敏纸片法（K－B法），从129株临床分离的金黄色葡萄球菌筛选对甲氧西林和氟喹诺酮类药物的耐药菌株，用琼脂二倍稀释法对交叉耐药菌进行MIC测试，比较了加替沙星与环丙沙星等第二代氟喹诺酮类药物的耐药菌株，用琼脂二倍稀释法对交叉耐药菌进行MIC测试，比较了加替沙星与环丙沙星等第二代氟喹诺酮类药物的抗菌活性。用苯唑西林筛选三代自发突变株，比较环丙沙星、加替沙星对MRSA的抗菌活性。实验表明，苯唑西林、环丙沙星、氧氟沙星、左氧氟沙星对129株金黄色葡萄球菌的耐药率相似。体外活性表明，加替沙星比环丙沙星等第二代氟喹诺酮类药物的抗菌活性强，抗MRSA菌株的活性较强；敏感金黄色葡萄球菌发生加替沙星耐药的突变频率在所试药物中也是最低的。说明加替沙星比环丙沙星等第二代氟喹诺酮类药物的抗菌活性得到明显提高。     

A novel polycationic analogue of gratisin with antibiotic activity against both Gram-positive and Gram-negative bacteria

A novel polycationic analogue of gratisin, cyclo(-Val-Orn-Leu-D-Phe-Pro-D-Lys-)2, was designed and synthesized, which exhibited strong activity against all Gram-positive and Gram-negative bacteria tested. Its activity against Pseudomonas aeruginosa IFO 3080 was two times higher than gramicidin S.     

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.     

夫西地酸对革兰阳性球菌的体外敏感性分析

摘要：目的检测夫西地酸对临床常见革兰阳性球菌的体外抗菌活性。方法用纸片扩散法检测夫西地酸对葡萄球菌和肠球菌的抑菌活性，并与其他常用抗生素比较。同时用琼脂稀释法检测部分菌株的夫西地酸最低抑菌浓度（MIC）。结果在121株菌株中MRSA34株，MRCNS41株，粪肠球菌15株，屎肠球菌10株。对夫西地酸的耐药率分别为2．9％、4．8％、100．0％和100．0％，略高于万古霉素，明显低于其他常用的抗生素（如红霉索、头孢唑林，环丙沙星等）。夫西地酸对MRSA、MRCNS的抗菌活性明显高于肠球菌。结论夫西地酸对MRS有较高的体外抗菌活性。夫西地酸对肠球菌并无杀菌作用。     

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％。