莫西沙星类似物的合成及其体内外抗菌活性

目的合成具有良好抗菌活性的莫西沙星类似物。方法以盐酸莫西沙星为原料,先与甲基乙烯酮发生加成反应生成N-(3-氧代-1-正丁基)莫西沙星(1),接着经氧化并重排及中和反应得到N-羟基莫西沙星(2)。测定化合物1和2的体内外抗菌活性。结果1的体外活性与对照药莫西沙星基本相当,且优于2(P<0.05);1和2对试验菌株所致小鼠系统感染均具有疗效,其中1的体内疗效与对照药莫西沙星基本相当(P>0.05),且优于2(P<0.05)。结论在莫西沙星7-位侧链的亚氨基上引入3-氧代-1-正丁基后其活性基本保持,但引入羟基后其活性明显降低。     

水产品中多种氟喹诺酮类药物残留的HPLC测定法

目的建立多种喹诺酮类（FQs）药物同时检测的高效液相色谱方法，建立水产品中（FQs）药物残留提取的前处理方法。方法研究水产品中喹诺酮类药物检测的最佳提取条件，液相色谱条件和荧光检测参数等。结果在该实验条件下，7种FQs类药物检测线性范围0.01～0.50mg/L（沙拉沙星0.10-5.0mg/1），最低检出限0.08-0.36μg/kg，变异系数1.5％～8.6％，样品加标回收率64.0％-93.4％。结论该方法能同时检测水产品中多种（FQs）药物残留，简单、快速、精密度较好、准确灵敏度较高，结果较满意。     

Association between proline-requiring auxotype and fluoroquinolone resistance in Neisseria gonorrhoeae isolated in Japan

We examined the association between auxotype and fluoroquinolone resistance in Neisseria gonorrhoeae isolated in Fukuoka, Japan, and investigated whether the prevalence of fluoroquinolone-resistant N. gonorrhoeae isolates was caused by the dissemination of the same clone in the community. We examined the antimicrobial susceptibility of 294 N. gonorrhoeae, isolates obtained during three different periods in Fukuoka, Japan, and 89 isolates of N. gonorrhoeae, classified by the presence of amino-acid substitutions in the quinolone resistance-determining regions (QRDRs) of GyrA and ParC proteins, to various agents, and we examined the auxotypes of the isolates. In 22 isolates with amino-acid substitutions within QRDRs in GyrA and ParC, pulsed-field gel electrophoresis analysis was performed. The proportion of fluoroquinolone-resistant isolates (ciprofloxacin, minimum inhibitory concentration [MIC] > or = 1 microg/ml) in 1998 (23.9%) was significantly higher than that in 1992-1993 (0%). The proportion of proline-requiring isolates increased significantly, from 4.4% in 1992-1993 to 54.5% in 1998. The ciprofloxacin MIC90 for the proline-requiring isolates were 32- and 128-fold, respectively, higher than those for the prototrophic isolates and the arginine-requiring isolates. The proportion of isolates with amino-acid substitutions within the QRDRs in GyrA and ParC in the proline-requiring group (55.5%) was significantly higher than that in the prototrophic group (0%). Of the 22 isolates with amino-acid substitutions within the QRDRs in GyrA and ParC, 16 showed the same pulsed-field gel electrophoresis pattern. These results suggest that a close association exists between the increase in the proline-requiring isolates and the increase in the fluoroquinolone-resistant isolates in the gonococci isolated in Fukuoka, and that the prevalence of fluoroquinolone-resistant N. gonorrhoeae isolates with GyrA and ParC substitutions may be mainly caused by the dissemination of a single clone in the community.     

氟喹诺酮类药物治疗结核病

由于需联合用药和长疗程治疗 ,结核病的治疗依然存在许多困难 ,而临床能用的抗结核药物很少 ,急需新的抗结核药物。氟喹诺酮类药物在许多方面显示是一个理想的抗结核药物 ,对氟喹诺酮药物治疗结核病的实验室和临床资料进行了概述。     

In silico study of Moxifloxacin derivatives with possible antibacterial activity against a resistant form of DNA gyrase from Porphyromonas gingivalis

We performed a homology modeling of the structure of a non-mutated and mutated Ser83→Phe DNA gyrase of Porphyromonas gingivalis. The model presented structural features conserved in type II topoisomerase proteins. We designed and evaluated in silico structural modifications to the core of Moxifloxacin by molecular docking, predicted toxicity and steered molecular dynamics simulations (SMD). Our results suggest that 8D derivative of Moxifloxacin could present a strong inhibitory activity in Porphyromonas gingivalis bacteria that exhibits resistance to some conventional fluoroquinolone drugs. Also, our results suggest that hydrophobic radicals in the hydroxyl group at position 3 of the quinolone core would increase the antibacterial activity of the compound when a reported mutation Ser83→Phe is present in the DNA gyrase protein. In addition, new candidates that could have a higher antibacterial activity compared to Moxifloxacin in non-resistant bacteria are proposed.     

2008～2010年氟喹诺酮类抗菌药物应用分析

目的：了解氟喹诺酮类抗菌药物使用情况,为合理用药提供依据。方法：对2008～2010年氟喹诺酮类抗菌药物使用数量、消耗金额、用药频度和日均费用进行统计分析。结果：2008～2010年左氧氟沙星注射液用药频度相对较高,在2010年氟喹诺酮类抗菌药物销售金额有所下降。结论：近三年内氟喹诺酮类抗菌药物的使用情况基本一致,随着氟喹诺酮类抗菌药物耐药问题的日益严重,应加强临床抗菌药物合理应用的监督管理,以提高临床抗菌药物合理应用水平。     

Multiple transmissible genes encoding fluoroquinolone and third-generation cephalosporin resistance co-located in non-typhoidal Salmonella isolated from food-producing animals in China

The aim of this study was to identify genes conferring resistance to fluoroquinolones and extended-spectrum β-lactams in non-typhoidal Salmonella (NTS) from food-producing animals in China. In total, 31 non-duplicate NTS were obtained from food-producing animals that were sick. Isolates were identified and serotyped and the genetic relatedness of the isolates was determined by pulsed-field gel electrophoresis of XbaI-digested chromosomal DNA. Antimicrobial susceptibility was determined using Clinical and Laboratory Standards Institute methodology. The presence of extended-spectrum β-lactamase (ESBL) and fluoroquinolone resistance genes was established by PCR and sequencing. Genes encoded on transmissible elements were identified by conjugation and transformation. Plasmids were typed by PCR-based replicon typing. The occurrence and diversity of numerous different transmissible genes conferring fluoroquinolone resistance [qnrA, qnrD, oqxA and aac(6′)-Ib-cr] and ESBLs (CTX-M-27 and CTX-M-14), and which co-resided in different isolates and serovars of Salmonella, were much higher than in European countries. Furthermore, different plasmids encoded fluoroquinolone resistance (ca. 6 kb) and β-lactam resistance (ca. 63 kb) and these co-resided in isolates with mutations in topoisomerase genes (gyrA and parC) giving very resistant Salmonella. The presence of multidrug-resistant bacteria in food-producing animals in countries that export foodstuffs suggests that global transfer of antibiotic resistances from country to country on food is possible.