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 MIC90s of DX-619 were ≤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 MIC90s 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 MIC90s of DX-619 against Enterobacteriaceae (except for Escherichia coli) and glucose-nonfermenting bacilli were ≤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.