7-取代-1-乙基(2-氟乙基)-6,8-二氟-1,4-二氢-4-氧喹啉-3-羧酸的合成及抗菌活性

７取代１乙基（２氟乙基）６，８二氟１，４二氢４氧喹啉３羧酸的合成及抗菌活性鄢立刚徐炳祥马振瀛朱艳静杨倩华（沈阳市沈阳军区后勤部军事医学研究所，沈阳１１００３１；上海市第二军医大学药学院中西药研究室，上海２００４...     

First report of plasmid-mediated fluoroquinolone efflux pump QepA in Escherichia coli clinical isolate ST68, in South America

This is the first report of the presence of qepA1 efflux pump gene in Escherichia coli clinical isolate from Argentina, which was associated to other plasmid-mediated quinolone resistance determinants, such as aac(6′)-Ib-cr and qnrB10 and also quinolone resistance determining regions mutations.     

淋球菌对环丙氟哌酸的药物敏感度测定

为了解我国淋球菌对氟喹诺酮类药物的敏感性，以琼脂稀释法测定了１９９４年７月～１９９６年７月由４个城市分离的５３５株淋球菌对环丙氟哌酸的敏感性，环丙氟哌酸最小抑菌浓度的范围为０．００２～〉２ｍｇ／Ｌ，７３株（１３．６４％）对环丙氟哌酸耐药，４９株（９．１６％），对环丙氟哌酸敏感。４１３株（７７．１９％）为低敏，４个城市对氟喹诺酮耐药的淋球菌的比率介于７．４６％～２５．５５％，耐药菌株比率呈上升趋势，     

Can bacterial virulence factors predict antibiotic resistant Helicobacter pylori infection?

AIM To evaluate the association between virulence factor status and antibiotic resistance in Helicobacter pylori(H. pylori)-infected patients in Ireland. METHODS DNA was extracted from antral and corpus biopsies obtained from 165 H. pylori-infected patients. Genotyping for clarithromycin and fluoroquinolone-mediating mutations was performed using the Genotype Helico DR assay. cag A and vac A genotypes were investigated using PCR. RESULTS Primary, secondary and overall resistance rates for clarithromycin were 50.5%(n = 53/105), 78.3%(n = 47/60) and 60.6%(n = 100/165), respectively. Primary, secondary and overall resistance rates for fluoroquinolones were 15.2%(n = 16/105) and 28.3%(n = 17/60) and 20%(n = 33/165), respectively. Resistance to both antibiotics was 12.4%(n = 13/105) in treatment-na?ve patients, 25%(n = 15/60) in those previously treated and 17%(n = 28/165) overall. A cag A-positive genotype was detected in 22.4%(n = 37/165) of patient samples. The dominant vac A genotype was S1/M2 at 44.8%(n = 74/165), followed by S2/M2 at 26.7%(n = 44/165), S1/M1 at 23.6%(n = 39/165) and S2/M1 at 4.8%(n = 8/165). Primary clarithromycin resistance was significantly lower in cag A-positive strains than in cag A-negative strains [32%(n = 8/25) vs 56.3%(n = 45/80); P = 0.03]. Similarly, in patients infected with more virulent H. pylori strains bearing the vac A s1 genotype, primary clarithromycin resistance was significantly lower than in those infected with less virulent strains bearing the vac A s2 genotype, [41%(n = 32/78) vs 77.8%(n = 21/27); P = 0.0001]. No statistically significant association was found between primary fluoroquinolone resistance and virulence factor status.CONCLUSION Genotypic H. pylori clarithromycin resistance is high and cag A-negative strains are dominant in our population. Less virulent(cag A-negative and vac A S2-containing) strains of H. pylori are associated with primary clarithromycin resistance.     

盐酸洛美沙星软膏抗菌作用研究

目的:观察盐酸洛美沙星软膏的抗菌作用,为临床用药提供科学依据。方法:体外抗菌试验通过对金黄色葡萄球菌、表皮葡萄球菌、肺炎球菌、溶血性链球菌、草绿色链球菌、绿脓杆菌、大肠直杆菌、变形杆菌的体外抗菌作用进行研究。体内抗菌作用采用皮下注入细菌使之形成闭合性疖肿,软膏外敷治疗验证其抗菌作用。结果:盐酸洛美沙星软膏对革兰氏阴性菌具有较强的抑菌活力,其MIC90在2mL/L附近对大肠杆菌的活力尤强,对肺炎球菌和其他链球菌的抗菌作用相对弱些,对实验性小鼠皮肤感染金黄色葡萄球菌所致闭合性疖肿有治疗作用。结论:盐酸洛美沙星软膏具有很强的抗菌活性。     

Identification of environmentally biodegradable scaffolds for the benign design of quinolones and related substances

Many micropollutants, such as pharmaceuticals and other chemicals, are present globally in the aquatic environment. During effluent treatment and in the environment, transformations result in new chemicals of often unknown structure, fate, and toxicity. The design of chemicals, that can be fully mineralized or broken down into non-hazardous fragments, is considered a green chemistry approach avoiding such problems from the very beginning (“benign by design”). N-heterocycles are central lead scaffolds for many important chemicals and pharmaceuticals such as quinolines, isoquinolines, quinolones, fluoroquinolones, naphthyridones, and quinazolinones. Understanding their environmental biodegradability is mandatory for the design of greener derivatives. While the biodegradability of simple quinolines has already been reported in the literature, information on more complex azaarenes and other N-heterocycles is rather scarce.The goal of this study was to investigate the ready biodegradability of several N-heterocycles to identify biodegradable lead scaffolds. LC-HRMS studies were performed to identify possible metabolites. Out of the 84 tested substances, only 14 were readily biodegradable in either the closed bottle test (OECD 301D) or the manometric respiratory test (OECD 301F). Hydroxylation at the C2 position increased the biodegradation level of the quinolines generally and tolerated even fluorine in the molecule. Moreover, 4-oxo-1,4-dihydroquinoline-3-carboxylic acid has been tested as readily biodegradable. It is an important bioactive lead scaffold with many different applications, i.e., in antibiotics. All other quinolones containing the β-keto-carboxylic acid moiety were persistent, including their bioisosteres. The identified biodegradable scaffolds can be used to design new environmentally biodegradable molecules following green fragment-based design.