Antibacterial spectrum of a novel des-fluoro(6) quinolone, BMS-284756.

نویسندگان

  • J C Fung-Tomc
  • B Minassian
  • B Kolek
  • E Huczko
  • L Aleksunes
  • T Stickle
  • T Washo
  • E Gradelski
  • L Valera
  • D P Bonner
چکیده

The in vitro spectrum of a novel des-fluoro(6) quinolone, BMS-284756, was compared with those of five fluoroquinolones (trovafloxacin, moxifloxacin, levofloxacin, ofloxacin, and ciprofloxacin). BMS-284756 was among the most active and often was the most active quinolone against staphylococci (including methicillin-resistant strains), streptococci, pneumococci (including ciprofloxacin-nonsusceptible and penicillin-resistant strains), and Enterococcus faecalis. BMS-284756 inhibited approximately 60 to approximately 70% of the Enterococcus faecium (including vancomycin-resistant) strains and 90 to 100% of the Enterobacteriaceae strains and gastroenteric bacillary pathogens at the anticipated MIC susceptible breakpoint (</=4 microg/ml). Against the nonfermenters, BMS-284756 inhibited 90 to 100% of Pseudomonas fluorescens, Pseudomonas stutzeri, Stenotrophomonas maltophilia, Flavobacterium spp., and Acinetobacter spp. and 72% of Pseudomonas aeruginosa strains at 4 microg/ml. Against anaerobic bacteria, BMS-284756 was among the most active, inhibiting essentially all strains tested. It had very low MICs against the fastidious and atypical microbial species, in particular against mycoplasmas or ureaplasmas, Borrelia burgdorferi, chlamydia, and gonococci. These results indicate that with its broad antibacterial spectrum, BMS-284756 should be evaluated clinically for the treatment of community and nosocomial infections.

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منابع مشابه

In vitro activities of novel des-fluoro(6) quinolone BMS-284756 against mutants of Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus selected with different quinolones.

BMS-284756 (T-3811) is a novel quinolone that lacks a fluorine at the C-6 position. BMS-284756 has a broad spectrum of antibacterial activity (3, 7). The purpose of the present study was (i) to analyze the in vitro activity of the novel quinolone against mutants of Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus selected with marketed quinolones and (ii) to investiga...

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Staphylococcus aureus mutants selected by BMS-284756.

BMS-284756, a novel des-fluoro(6)-quinolone, was used to select for in vitro mutants of Staphylococcus aureus ISP794. Step mutants were obtained, and the quinolone resistance-determining regions of four target genes, gyrA, gyrB, grlA, and grlB, were sequenced. The data suggest that DNA gyrase is the primary target for BMS-284756 in S. aureus.

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The inhibition and selectivity of bacterial topoisomerases by BMS-284756 and its analogues.

Analogues of BMS-284756, a novel des-F(6)-quinolone, were synthesized and evaluated in order to determine the effects of modification of substituents on in vitro target inhibition. BMS-340281 (stereoisomer of BMS-284756), BMS-340280 (C-6 fluorinated analogue of BMS-284756), BMS-340278 (C-8-H derivative), BMS-433366 (C-8 methoxy analogue) and fluoroquinolone comparators were evaluated for antiba...

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In vitro activities of the des-fluoro(6) Quinolone BMS-284756 against aerobic and anaerobic pathogens isolated from skin and soft tissue animal and human bite wound infections.

BMS-284756, a new des-fluoro(6) quinolone, was very active against 240 aerobic and 180 anaerobic isolates from bite victims. It inhibited 403 of 420 (96%) isolates, including those of Moraxella spp., CDC group EF-4, and Eikenella corrodens at < or = 2 microg/ml and those of all Pasteurella spp. and Bergeyella zoohelcum at < or = 0.015 microg/ml. Fusobacterium russii and 6 of 11 Fusobacterium nu...

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Efficacies of BMS 284756 against penicillin-sensitive, penicillin-resistant, and quinolone-resistant pneumococci in experimental meningitis.

BMS 284756 penetrated well into inflamed meninges (44% +/- 11%) and produced good bactericidal activity (-0.82 +/- 0.22 Delta log(10) CFU/ml. h) in the treatment of experimental meningitis in rabbits due to a penicillin-sensitive strain. BMS 284756 monotherapy had a greater potency than the standard regimen of ceftriaxone and vancomycin (-0.49 +/- 0.08 Delta log(10) CFU/ml. h) against a penicil...

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عنوان ژورنال:
  • Antimicrobial agents and chemotherapy

دوره 44 12  شماره 

صفحات  -

تاریخ انتشار 2000