title: In vitro antibacterial activity of DX-619, a novel Des-F (6)-quinolone against clinical isolates in China.
abstract: The aim of the study was to investigate in vitro antibacterial activity and bactericidal effect of DX-619 and other nine comparators against 1,101 recently collected clinical bacterial isolates in China. The minimum inhibitory concentrations (MICs) of antimicrobials were determined by a CLSI recommended standard agar dilution method and the minimum bactericidal concentrations (MBCs) were examined by the broth dilution method. Time-kill curves against representative isolates of Staphylococcus aureus, enterococci, and Klebsiellia pneumoniae were also conducted. DX-619 exhibited excellent antibacterial activity against 1,101 clinical isolates, especially to multi-drug resistant Gram-positive cocci. The MIC(90)s of DX-619 were < or =0.016 and 0.125 mg/L against methicillin-sensitive and -resistant S. aureus, 0.062 and 0.125 mg/L against methicillin-sensitive and -resistant S. epidermidis, respectively, which were 8-512 and 64-128 fold lower than those of comparative fluoroquinolones. The MIC(90)s of DX-619 for penicillin-sensitive and -non-sensitive Streptococcus pneumoniae, Enterococcus faecalis and Enterococcus faecium were 0.016, 0.062, 0.25 and 0.5 mg/L, respectively. The MIC(90)s of DX-619 against Enterobacteriaceae (except for Escherichia coli) and glucose-nonfermenting bacilli were < or =4 mg/L, which were comparable to other comparators. MBCs and time-kill curves showed that DX-619 was a potent bactericidal agent. There was no significant inoculum effect on MICs. But the activities of DX-619 against S. aureus, K. pneumoniae and Pseudomonas aeruginosa were decreased by acidic pH and human serum. DX-619 was a potent antibacterial compound against multi-drug resistant bacteria including Gram-positive cocci, such as S. aureus and enterococci, which may warrant further exploration.
authors.affiliation: First Hospital, Peking University, Beijing, Chna. xiaoyonghong@bjmu.edu.cn
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Xiao
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhong
authors.forename: Weiwei
authors.initials: W
authors.lastname: Yang
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002681:China; D024901:Drug Resistance, Multiple, Bacterial; D008826:Microbial Sensitivity Tests; D011759:Pyrrolidines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; C505440:DX 619; D011759:Pyrrolidines; D015363:Quinolones