Exploring the Antimicrobial Efficacy of DK-507k: A Comparative Study of In Vitro and In Vivo Fluoroquinolone Activities

The comparative study of a new quinolone, DK-507k, against several others such as ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, sitafloxacin, and garenoxacin, revealed its strong antibacterial properties. It demonstrated similar effectiveness to sitafloxacin and was notably more potent compared to gatifloxacin, moxifloxacin, and garenoxacin when tested against Streptococcus pneumoniae, including methicillin-sensitive and resistant Staphylococcus aureus, and coagulase-negative staphylococci. Notably, DK-507k was either as effective or up to 4 times more potent against ciprofloxacin-resistant strains of S. pneumoniae, including clinical isolates and in vitro-selected mutants with specific mutations. It was also able to inhibit all ciprofloxacin-resistant strains of S. pneumoniae at a concentration of 1μg/ml. In a time-kill assay with S. pneumoniae, DK-507k showed a more bactericidal effect than gatifloxacin and moxifloxacin.

In terms of activity against the family Enterobacteriaceae, DK-507k's performance was on par with ciprofloxacin and up to 32 times higher than that of other tested quinolones. However, it was less active against Pseudomonas aeruginosa compared to sitafloxacin and ciprofloxacin, but still showed greater potency than levofloxacin, gatifloxacin, moxifloxacin, and garenoxacin.

In vivo tests showed that DK-507k was more effective than gatifloxacin and moxifloxacin in treating systemic infections caused by S. aureus, S. pneumoniae, and P. aeruginosa in mice. In a mouse model of pneumonia due to penicillin-resistant S. pneumoniae, subcutaneous administration of DK-507k demonstrated dose-dependent efficacy and was able to clear bacteria from the lungs, unlike gatifloxacin and moxifloxacin. In a rat model of urinary tract infection caused by a P. aeruginosa isolate, oral treatment with DK-507k was slightly more effective than ciprofloxacin. Furthermore, rats given DK-507k orally reached higher peak serum concentrations and higher cumulative urine concentrations than those given ciprofloxacin.

These findings suggest that DK-507k may offer significant advantages over other quinolones for treating a broad spectrum of community-acquired infections.