体内抗菌活性的盐酸沙拉沙星，一种新型氟喹诺酮类抗生素。

In vivo antibacterial activity of chinfloxacin, a new fluoroquinolone antibiotic.

机构信息

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

出版信息

J Antimicrob Chemother. 2012 Apr;67(4):955-61. doi: 10.1093/jac/dkr557. Epub 2011 Dec 29.

DOI:10.1093/jac/dkr557

PMID:22210757

Abstract

OBJECTIVES

To evaluate the in vivo antibacterial efficacy of chinfloxacin, a novel fluoroquinolone, in murine systemic and local infection models.

METHODS

The efficacy of chinfloxacin in systemic infection was evaluated in a mouse peritonitis model using isolates of methicillin-susceptible Staphylococcus aureus (MSSA, n = 3), methicillin-resistant Staphylococcus aureus (MRSA; n = 1), penicillin-intermediate Streptococcus pneumoniae (PISP; n = 1), penicillin-resistant S. pneumoniae (PRSP; n = 2), vancomycin-susceptible Enterococcus faecalis (VSE; n = 1), vancomycin-resistant E. faecalis (VRE; n = 2), Escherichia coli (n = 3) and Klebsiella pneumoniae (n = 2). The local infections included mouse pulmonary infections caused by penicillin-susceptible S. pneumoniae (PSSP; n = 1), PRSP (n = 1) and K. pneumoniae (n = 2).

RESULTS

In the mouse systemic infection model, chinfloxacin demonstrated potent activity against MSSA [50% effective dose (ED(50)) 2.28-4.15 mg/kg], MRSA (ED(50) 14.75 mg/kg), PISP (ED(50) 6.20 mg/kg), PRSP (ED(50) 3.51-5.03 mg/kg), VSE (ED(50) 25.02 mg/kg), VRE (ED(50) 5.18-15.39 mg/kg), E. coli (ED(50) 1.25-1.90 mg/kg) and K. pneumoniae (ED(50) 2.92-8.28 mg/kg). The therapeutic efficacy of chinfloxacin was generally similar to (P > 0.05) that of moxifloxacin, significantly higher (P < 0.01 or P < 0.05) than that of levofloxacin in Gram-positive isolate infections (MSSA, MRSA, PISP, PRSP, VSE and VRE), and less than that of levofloxacin against E. coli and K. pneumoniae infections (P < 0.01). In the mouse pulmonary infection model, chinfloxacin showed potent activity towards S. pneumoniae (higher than levofloxacin and ciprofloxacin) and K. pneumoniae (lower than levofloxacin and similar to or higher than ciprofloxacin) infections.

CONCLUSIONS

The results validated the potent efficacy of chinfloxacin in vivo. The high efficacy of chinfloxacin in murine systemic and local infections warrants investigation of its clinical use.

摘要

目的

评估新型氟喹诺酮类药物 - 克林沙星在小鼠全身和局部感染模型中的体内抗菌疗效。

方法

采用耐甲氧西林金黄色葡萄球菌（MSSA，n = 3）、耐甲氧西林金黄色葡萄球菌（MRSA；n = 1）、青霉素中介性肺炎链球菌（PISP；n = 1）、青霉素耐药性肺炎链球菌（PRSP；n = 2）、万古霉素敏感性粪肠球菌（VSE；n = 1）、万古霉素耐药性粪肠球菌（VRE；n = 2）、大肠杆菌（n = 3）和肺炎克雷伯菌（n = 2）的分离株，在小鼠腹膜炎模型中评估克林沙星对全身感染的疗效。局部感染包括青霉素敏感性肺炎链球菌（PSSP；n = 1）、PRSP（n = 1）和肺炎克雷伯菌引起的小鼠肺部感染。

结果

在小鼠全身感染模型中，克林沙星对 MSSA [50%有效剂量（ED（50））2.28-4.15 mg/kg]、MRSA（ED（50）14.75 mg/kg）、PISP（ED（50）6.20 mg/kg）、PRSP（ED（50）3.51-5.03 mg/kg）、VSE（ED（50）25.02 mg/kg）、VRE（ED（50）5.18-15.39 mg/kg）、大肠杆菌（ED（50）1.25-1.90 mg/kg）和肺炎克雷伯菌（ED（50）2.92-8.28 mg/kg）具有强大的活性。克林沙星的治疗疗效通常与莫西沙星相似（P > 0.05），显著高于（P < 0.01 或 P < 0.05）治疗革兰氏阳性分离株感染（MSSA、MRSA、PISP、PRSP、VSE 和 VRE）的左氧氟沙星，低于治疗大肠杆菌和肺炎克雷伯菌感染的左氧氟沙星（P < 0.01）。在小鼠肺部感染模型中，克林沙星对肺炎链球菌（高于左氧氟沙星和环丙沙星）和肺炎克雷伯菌（低于左氧氟沙星，与环丙沙星相似或高于环丙沙星）感染具有强大的活性。