In vitro and in vivo activities of DW-224a, a novel fluoroquinolone antibiotic agent.
OBJECTIVE
The objective of the present study was to assess the in vitro and in vivo activities of DW-224a in order to eventually use it as an antibiotic.


METHODS
DW-224a was compared with DW286, ciprofloxacin and trovafloxacin. MICs of DW-224a, DW286, ciprofloxacin and trovafloxacin were determined against several groups of clinical isolates. In addition, intraperitoneal infection was induced with various organisms in mice. Test compounds were administered once orally to mice immediately after infection. The 50% protective dose (PD50) was calculated from the survival rates on day 7 after infection.


RESULTS
Against Gram-positive bacteria, the in vitro activity of DW-224a was stronger than those of ciprofloxacin and trovafloxacin, but slightly weaker than that of DW286. Against Gram-negative bacteria, the activity of DW-224a was similar to those of trovafloxacin and DW286, but weaker than that of ciprofloxacin. In experimental systemic infections in mice with various organisms, like DW286, DW-224a demonstrated potent activity against Gram-positive bacteria and somewhat less activity against Gram-negative bacteria.


CONCLUSIONS
DW-224a has a broad spectrum of antimicrobial activity, which is especially potent against Gram-positive bacteria.
Kwon
Ae-Ran
AR
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
Min
Yu-Hong
YH
Ryu
Jei-Man
JM
Choi
Dong-Rack
DR
Shim
Mi-Ja
MJ
Choi
Eung-Chil
EC
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C480202:zabofloxacin