Abstract
The in vitro activity of the new fluoroquinolone CP-99,219 [7-(3-azabicyclo[3.1.0]hexyl)naphthyridone] was compared with those of four other quinolones against 541 gram-negative, 283 gram-positive, and 70 anaerobic bacterial isolates. CP-99,219 inhibited 90% of many isolates in the family Enterobacteriaceae at a concentration of < or = 0.25 micrograms/ml (range, < 0.008 to 1 microgram/ml), an activity comparable to those of tosufloxacin and sparfloxacin and two times greater than that of temafloxacin. Ninety percent of the Proteus vulgaris, Providencia rettgeri, Providencia stuartii, and Serratia marcescens isolates were inhibited by 0.5 to 2 micrograms of CP-99,219 per ml. CP-99,219 inhibited 90% of the Pseudomonas aeruginosa and Haemophilus influenzae isolates at 1 and 0.015 micrograms/ml, respectively. The compound inhibited methicillin-susceptible Staphylococcus aureus at 0.06 micrograms/ml, whereas a ciprofloxacin concentration of 1 microgram/ml was required to inhibit these organisms. CP-99,219 inhibited 90% of methicillin-resistant S. aureus isolates at a concentration of < or = 4 micrograms/ml, while ciprofloxacin and temafloxacin had MICs against these isolates of > 16 micrograms/ml. Streptococci were inhibited by < or = 0.25 micrograms/ml, an activity comparable to that of tosufloxacin. CP-99,219 was eight times more active than ciprofloxacin against Streptococcus pneumoniae. Bacteroides species were inhibited by CP-99,219 at a concentration of 2 micrograms/ml, whereas inhibition of these species required 4- and 16-microgram/ml concentrations of tosufloxacin and ciprofloxacin, respectively. The MBCs of CP-99,219 ranged from two to four times the MICs, and inoculum size had a minimal effect on MIC. CP-99,219 was active against P. aeruginosa at pH 5.5, with only a fourfold increase in MIC compared with values obtained at pH 7.5. The addition of up to 9 mM Mg(2+) increased the MIC range from 0.03 to 0.06 microgram/ml to 0.12 to 0.5 microgram/ml. In view of its excellent in vitro activity against both gram-positive and gram-negative bacteria, CP-99,219 merits further study to determine it's clinical pharmacologic properties and potential for therapeutic use.
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- Blumberg H. M., Rimland D., Carroll D. J., Terry P., Wachsmuth I. K. Rapid development of ciprofloxacin resistance in methicillin-susceptible and -resistant Staphylococcus aureus. J Infect Dis. 1991 Jun;163(6):1279–1285. doi: 10.1093/infdis/163.6.1279. [DOI] [PubMed] [Google Scholar]
- Eliopoulos G. M., Klimm K., Eliopoulos C. T., Ferraro M. J., Moellering R. C., Jr In vitro activity of CP-99,219, a new fluoroquinolone, against clinical isolates of gram-positive bacteria. Antimicrob Agents Chemother. 1993 Feb;37(2):366–370. doi: 10.1128/aac.37.2.366. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gooding B. B., Jones R. N. In vitro antimicrobial activity of CP-99,219, a novel azabicyclo-naphthyridone. Antimicrob Agents Chemother. 1993 Feb;37(2):349–353. doi: 10.1128/aac.37.2.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hirschhorn L., Neu H. C. Factors influencing the in vitro activity of two new aryl-fluoroquinolone antimicrobial agents, difloxacin (A-56619) and A-56620. Antimicrob Agents Chemother. 1986 Jul;30(1):143–146. doi: 10.1128/aac.30.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jorgensen J. H., Redding J. S., Maher L. A., Howell A. W. Improved medium for antimicrobial susceptibility testing of Haemophilus influenzae. J Clin Microbiol. 1987 Nov;25(11):2105–2113. doi: 10.1128/jcm.25.11.2105-2113.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaatz G. W., Seo S. M., Ruble C. A. Mechanisms of fluoroquinolone resistance in Staphylococcus aureus. J Infect Dis. 1991 May;163(5):1080–1086. doi: 10.1093/infdis/163.5.1080. [DOI] [PubMed] [Google Scholar]
- Neu H. C., Novelli A., Chin N. X. Comparative in vitro activity of a new quinolone, AM-1091. Antimicrob Agents Chemother. 1989 Jul;33(7):1036–1041. doi: 10.1128/aac.33.7.1036. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neu H. C. Quinolone antimicrobial agents. Annu Rev Med. 1992;43:465–486. doi: 10.1146/annurev.me.43.020192.002341. [DOI] [PubMed] [Google Scholar]
- Pearson R. D., Steigbigel R. T., Davis H. T., Chapman S. W. Method of reliable determination of minimal lethal antibiotic concentrations. Antimicrob Agents Chemother. 1980 Nov;18(5):699–708. doi: 10.1128/aac.18.5.699. [DOI] [PMC free article] [PubMed] [Google Scholar]