Antibrucella Activity of Quinolone Sparfloxacin

Background: Sparfloxacin is a new fluoroquinolone with excellent in vitro activity against a variety of Gram-positive and Gram-negative bacteria.
Methods: In vitro antibacterial activity of this new drug was tested against 139 strains of Brucella melitensis. These strains were isolated from 138 patients at a major tertiary care referral center in Riyadh, Saudi Arabia.
Results: Seven percent of the strains were inhibited by 0.06 mg per L and 99% by 0.12 mg per L of sparfloxacin. Of the five other fluoroquinolones tested, ciprofloxacin, norfloxacin, pefloxacin, and fleroxacin exhibited comparable or slightly higher minimal inhibitory concentrations values. They inhibited the growth of 138 of the 139 isolates at 0.25–0.5 mg per L. Rufloxacin required 2–8 mg per L to inhibit 138 of the 139 strains tested. One of the isolates, which had previously developed resistance to ciprofloxacin during therapy with this drug, with a rise in MIC from 0.06 mg per L to >5.0 mg per L, exhibited cross-resistance to sparfloxacin and other fluoroquinolones.
Conclusion: Sparfloxacin exhibited excellent in vitro activity against clinical isolates of Brucella. Clinical trials are warranted to determine its potential in the treatment of brucellosis.     

Quinolone derivatives as antitubercular drugs

New chemotherapeutic drugs are the need to improve tuberculosis (TB) control particularly due to the emergence of multidrug-resistant strains and extensively drug-resistant strains of TB. These antitubercular compounds have different chemical moieties in their structure. Quinolones are generally used against many Gram-positive and Gram-negative bacteria. They are also active against atypical mycobacteria. Some quinolones (ciprofloxacin, levofloxacin, etc.) inhibit strains of Mycobacterium tuberculosis at concentrations <2.0 μg/mL. Fluoroquinolones are an important recent addition to the drugs available for TB, especially for strains that are resistant to first-line agents. The present review provides an overview of the drugs that are being used have quinolone moieties in TB treatment.     

喹诺酮类抗生素的快速系统鉴别方法的探讨

喹诺酮类抗生素由于其抗菌谱广，杀菌力强，目前临床应用非常广泛。由于该类抗生素母核结构相似，同类化合物化学反应相同，若用液相色谱方法进行不同的品种鉴别，则又受仪器条件的限制，不适用于现场快检。为了有力打击掺假的现象，我们对喹诺酮类抗生素进行了快速系统鉴别方法的研究，建立了以颜色反应与薄层色谱相结合的喹诺酮类抗生素快速的系统鉴别方法。经试验该方法具有使用仪器设备简单，样品消耗量小，检测速度快，结果准确，操作安全的特点，尤为适合于基层现场打假工作的需要，且此快速检测技术能够提高假劣药品的检出率，初步实现“靶向抽验”的目的。     

Quinolone resistance in the food chain

Antimicrobials are used in pet animals and in animal husbandry for prophylactic and therapeutic reasons and also as growth promoters, causing selective pressure on bacteria of animal origin. The impact of quinolones or quinolone-resistant bacteria on the management of human infections may be associated with three different scenarios. (i) Quinolone-resistant zoonotic bacterial pathogens are selected and food is contaminated during slaughter and/or preparation. (ii) Quinolone-resistant bacteria non-pathogenic to humans are selected in the animal. When the contaminated food is ingested, the bacteria may transfer resistance determinants to other bacteria in the human gut (commensal and potential pathogens). And (iii) quinolones remain in residues of food products, which may allow the selection of antibiotic-resistant bacteria after the food is consumed. In this review, we analyse the abovementioned aspects, emphasising the molecular basis of quinolone resistance in Escherichia coli, Salmonella spp. and Campylobacter spp.     

伤寒杆菌耐喹诺酮类机理研究

以伤寒杆菌临床分离的喹诺酮类敏感株 S2 75与其诱导耐药株 RG1 与 RG2 ,对有关伤寒杆菌耐喹诺酮类机制进行了研究。结果发现与伤寒杆菌 S2 75相比较 ,RG1 与 RG2 对喹诺酮类、四环素、氯霉素敏感性明显降低 ,对头孢唑林 ,亚胺培南敏感性有所增加。喹诺酮类对 DNA旋转酶活性 5 0 %抑制剂量 ,RG1 与RG2 较 S2 75呈 3～ 8倍增加 ,S2 75与 RG1 、RG2 旋转酶亚单位交叉重建及 DNA旋转酶 A亚单位基因 (gyr A)喹诺酮耐药决定区 PCR- RFL P分析表明 A亚单位变异为耐药原因之一。细菌对氧氟沙星聚积测定 ,RG1 与RG2 分别为 S2 75之 1/ 2与 1/ 8,经 CCCP处理后 ,分别上升为 S2 75原水平与 S2 75之 1/ 2水平。外膜蛋白分析示 RG2 5 5 k D蛋白带消失 ,同时伴生化反应改变。表明伤寒杆菌耐喹诺酮类机制存在 DNA旋转酶变异 ,药物主动外运及外膜通透性改变。     

Quinolone antimicrobial agents: structure-activity relationships.

The rapid growth in the quinolone research changed the whole face of the previous SAR concepts. So far structural modifications at all positions of the quinolone nucleus except the 4-oxo group have successfully lead to the discovery of potent antimicrobial agents. At position 1, ethyl and its bioisosteres such as fluoroethyl, methylamino, methoxy, etc, are optimal substituents while some groups with a tert.-carbon atom directly connected with N-1 position such as tert.-butyl, phenyl, etc. are also promising for the activity of the quinolone compounds. Steric bulk is no longer considered as the only factor which influences the activity of the compounds. However, it could only be answered by further research how big such steric bulk tolerance at position 1 would be and what is the precise role that the N-1 substituents play in the mechanism of action of the quinolones. Fluorination has been extensively employed as a modifying technique to almost all possible positions of the quinolone nucleus. While being maintained at C-6, a fluorine atom was also introduced to C-5 and C-8 to produce potent analogues. Fluorination of N-1 substituents, e.g., fluoroethyl, fluorophenyl, etc., and C-7 substituents, e.g. 2-((fluoromethyl)piperazinyl and fluorohomopiperazinyl, etc., yielded also a handful of potent quinolones. Amino-and chloro groups are found to be beneficial for positions 5 and 8, respectively. The "medium size" concept concerning the 7-substituents is no longer valid. Numerous potent quinolones with a "large" group substituted on position 7 have been discovered. A certain amount of free rotation in the 7-substituents appears to emerge as an important factor which influences the activity of the compounds. Some radical modifications in 7-substituents, e.g. C--C linkage between the nucleus and 7-substituents, afforded new insight into the SAR of quinolones. A planarity between the 4-oxo group and 3-carboxylic group may be important for binding to the DNA gyrase as demonstrated by a group of enolized isothiazoloquinolone derivatives. Further research will surely lead to the better understanding on the mechanism of action of quinolones as well as the discovery of analogues with better activity features, lower adverse effects and more favourable pharmacokinetic properties.     

喹诺酮类抗菌剂结构与不良反应之间的关系

简要介绍喹诺酮类抗菌剂的毒性和近年来一些具有代表性的不成功的喹诺酮类药物，并在此基础上分析了喹诺酮类药物的结构和不良反应之间的关系。提出了自己的观点。     

喹诺酮类抗菌药的研究新进展

喹诺酮类化合物是一类临床广泛使用的广谱、高效、低毒抗感染药物。随着耐药菌的迅速增加,抗感染治疗正面临重大挑战。因此,对喹诺酮类化合物进行结构修饰以获得活性更强、抗菌谱更广、毒性更小的抗感染药物仍是抗菌药研究领域的重要课题之一。综述近年来喹诺酮类化合物结构修饰及抗菌活性研究的新进展。     

普卢利沙星--新一代氟喹诺酮类抗菌药

普卢利沙星(NM441)是氟喹诺酮类抗菌药物NM394的前体药物。体内外实验和临床研究表明,NM441对G+菌和G-菌均具有强的广谱抗菌活性,安全性较好,适用于呼吸、泌尿等多种组织和器官系统细菌感染的治疗。并对其药物动力学、药理作用和临床应用等方面的研究进行了简要总结。     

无氟喹诺酮类抗菌药研究进展

目的 综述一类新型母核上无氟喹诺酮类抗菌药的的药效学/药动学及安全性的研究进展.方法 查阅近年来国内外相关文献30篇,对其进行归纳、总结和分析.结果 目前,全球已上市三种无氟喹诺酮类抗菌药,为新型广谱喹诺酮类抗菌药,保持了喹诺酮类抗菌药对革兰阴性菌的抗菌活性,同时对革兰阳性菌的抗菌活性也明显增强,且由于不含氟元素,其安全性更高,更少引起过敏反应和光毒性.结论 喹诺酮类抗菌药是临床上使用的一类十分重要的抗菌药,新型无氟喹诺酮抗菌药在全球面临耐药菌的威胁下值得进一步研究开发.     

喹诺酮类抗菌药物的临床不良反应

目的综述喹诺酮类抗菌药物所致临床不良反应的情况,为临床合理使用抗菌类药物提供警示,预防该类药物不良反应的发生。方法对国内外近期公开报道的喹诺酮类抗菌药物临床不良反应进行总结与分析。结果喹诺酮类药物的主要临床不良反应有消化系统反应、过敏反应、光敏反应、中枢神经系统反应、心血管系统反应、肝、肾功能损害、血液系统反应、软骨毒性和肌腱损伤以及影响血糖等。结论喹诺酮类抗菌药物引起的不良反应症状多,涉及系统广泛,有的后果严重,临床医生应严格掌握适应证,高度重视药品不良反应的监测,发现不良反应及时采取有效措施,提高用药的安全性。     

喹诺酮类药物不良反应监测

目的：总结分析广州军区武汉总医院12年来喹诺酮类药物不良反应情况，为临床合理用药提供依据。方法：查阅该院1989-2001年喹诺酮类药物不良反应报表。结果：喹诺桐类不良反应有逐年增加趋势，总数占全院抗菌药物不良反应报表的32%，皮疹，静脉炎等不良反应最多见，次为循环系统和消化系统的不良反应。结论：临床应用喹诺酮类药物应严格掌握适应证，疗程等，发现不良反应应及时停药并尽早采取治疗措施。     

铜绿假单胞菌对喹诺酮类药物耐药作用的研究

目的研究铜绿假单胞茵对喹诺酮类药物的耐药性及其机制。方法收集、分离及鉴定从四川大学华西医院分离的27株铜绿假单胞茵,测定5种喹诺酮类药物的最低抑茵浓度（MIC）及碳酰氰基-对-氯苯腙（CCCP）对喹诺酮类药物的体外抗茵活性。采用RT—PCR方法扩增铜绿假单胞茵外膜蛋白基因oprM,PCR方法扩增外排蛋白阻遏基因mexR、质粒qnr基因。结果5种喹诺酮类药物中没有一种对27株铜绿假单胞菌完全敏感,均出现了比较高的耐药水平,且具有交叉耐药性。CCCP能使部分耐药 细菌的MIC逆转。耐药菌株oprM基因在RNA水平上表达增加,mexR经DNA测序表明临床分离铜绿假单胞菌主动外排耐药株基因在编码66住氨基酸处发生了碱基突变oqnr基因经PCR扩增后电泳无条带显示,表明没有质粒介导的耐药产生。结论成都地区铜绿假单胞菌临床分离株对5种喹诺酮类药物呈现交叉耐药。主动外排是导致铜绿假单胞菌耐药性的重要因素。     

喹诺酮类抗菌药物的合理应用

自1962年第一个喹诺酮类药物萘啶酸问世，及1984年FDA批准第一个喹诺酮类抗菌药物诺氟沙星上市，虽然该类药物使用时间相对较短，但基于其药效学药动学特性优良，口服和静脉剂型兼备，且因新品种研发活跃，已发展到第四代，抗菌活性和抗菌谱扩大，毒性得到降低，因此在临床广泛应用于治疗感染性疾病，疗效优异。     

喹诺酮类药物的作用机制耐药机制及研究进展

喹诺酮类药物主要作用于DNA拓扑异构酶,阻碍DNA复制,发挥广谱抗菌作用。但该类药物的耐药问题日益严重,耐药菌株频现。本文综述喹诺酮类药物的耐药机制及其研究进展。     

质粒介导的喹诺酮类耐药机制研究进展

质粒介导的喹诺酮类抗菌药物的耐药是近十几年来新发现的一类细菌耐药机制,可在肠杆菌科细菌中水平传播,引起的感染不易控制,导致院内感染大范围流行.本文对质粒介导喹诺酮耐药基因的发现及种类、遗传背景、对喹诺酮类的作用机制及其临床意义等方面进行综述,为研究新型喹诺酮类抗菌药物及抗感染治疗中合理使用氟喹诺酮类抗菌药物提供依据.     

Quinolone derivatives and their antifungal activities: An overview

More than 300 million people suffer from the incidence of life‐threatening invasive fungal infections, resulting in over 1.35 million deaths annually. Currently, the antifungal agents available in clinics are rather limited, and the rapid development of resistance to the existing antifungal drugs has further aggravated mortality. Quinolones possess a broad spectrum of chemotherapeutic properties and demonstrate considerable antifungal activities as well. Various quinolone derivatives have been screened for their antifungal activities, and some of them exhibit excellent potency against both drug‐susceptible and drug‐resistant fungi. This review aims to outline the recent advances in quinolone derivatives as potential antifungal agents and summarize the structure–activity relationship, to provide insights for the rational design of more active candidates.     

喹诺酮类药物的降解物结构确证

氧氟沙星，盐酸洛美沙星及氟罗沙星在２ｍｏｌ／Ｌ盐酸液中长时间加热回流，分离纯化后所得的降解物，经ＭＳＨＮＭＲ，＾１３ＣＮＭＲ，ＩＲ及ＵＶ测试与解析，并与原药比较，确证它们是原药的脱羧物。