Abstract
The in vitro activity of T-3761, a new fluoroquinolone antimicrobial agent which has an oxazine ring structure with a cyclopropyl moiety at C-10, was compared with those of other agents against 2,854 clinical isolates. T-3761 had a broad spectrum of activity and had potent activity against gram-positive and -negative bacteria. The MICs of T-3761 against 90% of the methicillin-susceptible Staphylococcus aureus, methicillin-susceptible and -resistant Staphylococcus epidermidis, and Clostridium spp. tested were 0.39 to 6.25 micrograms/ml. Its activity was comparable to those of ciprofloxacin and ofloxacin and four- to eightfold greater than those of norfloxacin and fleroxacin, but its activity was two- to eightfold less than that of tosufloxacin. Some isolates of ciprofloxacin-resistant S. aureus (MIC of ciprofloxacin, greater than or equal to 3.13 micrograms/ml) were still susceptible to T-3761 (MIC of T-3761, less than or equal to 0.78 micrograms/ml). The MICs of T-3761 against 90% of the streptococci and enterococci tested were 3.13 to 100 micrograms/ml. Its activity was equal to or 2- or 4-fold greater than those of norfloxacin and fleroxacin, equal to or 2- or 4-fold less than those of ofloxacin and ciprofloxacin, and 4- to 16-fold less than that of tosufloxacin. The activity of T-3761 against gram-negative bacteria was usually fourfold greater than those of norfloxacin, ofloxacin, and fleroxacin. Many isolates which were resistant to nonfluoroquinolone agents, such as minocycline- or imipenem-resistant S. aureus, ceftazidime-resistant members of the family Enterobacteriaceae, gentamicin- or imipenem-resistant Pseudomonas aeruginosa, and ampicillin-resistant Haemophilus influenzae and Neisseria gonorrhoeae, were susceptible to T-3761. The MBCs of T-3761 were either equal to or twofold greater than the MICs. The number of viable cells decreased rapidly during incubation with T-3761 at one to four times the MIC. At a concentration of four times the MIC, the frequencies of appearance of spontaneous mutants resistant to T-3761 against S. aureus, Escherichia coli, Serratia marcescens, and P. aeruginosa were 2.2 x 10(-8) to less than or equal to 1.2 x 10(-9). The 50% inhibitory concentrations of T-3761 for DNA gyrases isolated from E. coli and P. aeruginosa were 0.88 and 1.9 micrograms/ml, respectively.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aoyama H., Sato K., Fujii T., Fujimaki K., Inoue M., Mitsuhashi S. Purification of Citrobacter freundii DNA gyrase and inhibition by quinolones. Antimicrob Agents Chemother. 1988 Jan;32(1):104–109. doi: 10.1128/aac.32.1.104. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fujimoto T., Mitsuhashi S. In vitro antibacterial activity of DR-3355, the S-(-)-isomer of ofloxacin. Chemotherapy. 1990;36(4):268–276. doi: 10.1159/000238777. [DOI] [PubMed] [Google Scholar]
- Gellert M., Fisher L. M., O'Dea M. H. DNA gyrase: purification and catalytic properties of a fragment of gyrase B protein. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6289–6293. doi: 10.1073/pnas.76.12.6289. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gellert M., Mizuuchi K., O'Dea M. H., Itoh T., Tomizawa J. I. Nalidixic acid resistance: a second genetic character involved in DNA gyrase activity. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4772–4776. doi: 10.1073/pnas.74.11.4772. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hane M. W., Wood T. H. Escherichia coli K-12 mutants resistant to nalidixic acid: genetic mapping and dominance studies. J Bacteriol. 1969 Jul;99(1):238–241. doi: 10.1128/jb.99.1.238-241.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inoue Y., Sato K., Fujii T., Hirai K., Inoue M., Iyobe S., Mitsuhashi S. Some properties of subunits of DNA gyrase from Pseudomonas aeruginosa PAO1 and its nalidixic acid-resistant mutant. J Bacteriol. 1987 May;169(5):2322–2325. doi: 10.1128/jb.169.5.2322-2325.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kojima T., Inoue M., Mitsuhashi S. In vitro activity of AT-4140 against clinical bacterial isolates. Antimicrob Agents Chemother. 1989 Nov;33(11):1980–1988. doi: 10.1128/aac.33.11.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kojima T., Inoue M., Mitsuhashi S. In vitro activity of AT-4140 against quinolone- and methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1990 Jun;34(6):1123–1127. doi: 10.1128/aac.34.6.1123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ozaki M., Matsuda M., Tomii Y., Kimura K., Kazuno K., Kitano M., Kise M., Shibata K., Otsuki M., Nishino T. In vitro antibacterial activity of a new quinolone, NM394. Antimicrob Agents Chemother. 1991 Dec;35(12):2490–2495. doi: 10.1128/aac.35.12.2490. [DOI] [PMC free article] [PubMed] [Google Scholar]