TANAKA M, AKASAKA T, ONODERA Y, YOSHIHARA K, TAKEMURA M, SATO K; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. F-552.

Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan

DQ-113, a novel quinolone, showed a potent antibacterial activity against Gram-positive bacteria especially Staphylococcus aureus including methicillin-resistant strains. The increase in the clinical use of fluoroquinolones has led to the widespread emergence of fluoroquinolone-resistant strains especially in MRSA, thus we investigated the development of resistance to DQ-113 in five MRSA strains isolated in Japan. The MIC values of DQ-113 against the strains selected after 14 serial exposures to sub-inhibitory concentrations of the compound were from 0.012 to 0.05 microg/ml, which were 1 to 4 times the initial MICs, while the MICs of levofloxacin, sitafloxacin, ciprofloxacin, and clinafloxacin raised 2-4, 1-16, 8-64, and 2-8 times after 14 passages, respectively. DQ-113 also inhibited the growth of all resistant strains including ciprofloxacin-selected mutants (ciprofloxacin MIC, >200 microg/ml) at 0.20 microg/ml. To clarify the potent antibacterial activity and the low incidence of resistance, the uptake in the S. aureus cells and the inhibitory activity of DQ-113 against target enzymes were determined. The amount of DQ-113 was at least 4.0 times higher than those of sitafloxacin and clinafloxacin in S. aureus FDA 209-P and NorA-overexpressing strain. The inhibitory activity of DQ-113 against wild-type and mutated topoisomerase IV was the highest among the quinolones tested. From these results, DQ-113 may be effective against the infections caused by ciprofloxacin-resistant and/or multi-drug resistant S. aureus.

Publication Types:

• Meeting Abstracts

Keywords:

• Anti-Bacterial Agents
• Ciprofloxacin
• DNA Topoisomerase IV
• DQ113
• Fluoroquinolones
• Gram-Positive Bacteria
• In Vitro
• Japan
• Microbial Sensitivity Tests
• Ofloxacin
• Quinolones
• Staphylococcal Infections
• Staphylococcus aureus
• clinafloxacin
• sitafloxacin

Other ID:

• GWAIDS0030424

UI: 102270061

From Meeting Abstracts