and Activities of DS-2969b, a Novel GyrB Inhibitor, and Its Water-Soluble Prodrug, DS11960558, against Methicillin-Resistant Staphylococcus aureus.

DS-2969b is a novel GyrB inhibitor under clinical development. In this study, the activity of DS-2969b and the activities of DS-2969b and its water-soluble prodrug, DS11960558, against methicillin-resistant (MRSA) were evaluated. DS-2969b inhibited the supercoiling activity of DNA gyrase and the decatenation activity of its topoisomerase IV.

In vivo antianaerobe activity of DS-8587, a new fluoroquinolone, against Fusobacterium necrophorum in a mouse model.

DS-8587 is a novel parenteral fluoroquinolone, which has an activity equivalent to sitafloxacin against various pathogens including anaerobes. We examined the in vivo anti-anaerobic activity of DS-8587, and compared it with that of levofloxacin (LVFX), using a murine model of Fusobacterium necrophorum-induced liver abscess developed via blood borne infection. Mice with liver abscess infection caused by F.

Anti-multidrug-resistant Acinetobacter baumannii activity of DS-8587: In vitro activity and in vivo efficacy in a murine calf muscle infection model.

DS-8587 is a novel broad-spectrum fluoroquinolone with extended antimicrobial activity against both Gram-positive and Gram-negative pathogens. In this study, we evaluated the in vitro and in vivo antibacterial activity of DS-8587 against multidrug-resistant (MDR) Acinetobacter baumannii. The MIC range of DS-8587 against MDR A.

[Therapeutic efficacy of levofloxacin against a model of replicable Legionella pneumophila lung infection in DBA/2 mice].

The in vitro and in vivo antibacterial activities of levofloxacin (LVFX), a quinolone antibacterial, against clinically isolated Legionella pneumophila were investigated in comparison with those of existing antimicrobial agents approved for legionnaires disease. The minimum inhibitory concentrations (MICs) of the agents against 42 strains of L. pneumophila isolated in Japan were determined using agar dilution methods with buffered starch yeast extract agar.

[Novel model of replicative Legionella pneumophila lung infection in DBA/2 mice].

We present here a new model of Legionella pneumophila lung infection in DBA/2 mice. By intranasal inoculation with 106 colony-forming units of L. pneumophila strain suzuki serogoup 1, persistent non-lethal lung infection was established as reflected by the detection of more than 10(4) CFU/lung of the organism 14 days after infection.

In vitro and in vivo antibacterial activities of DC-159a, a new fluoroquinolone.

DC-159a is a new 8-methoxy fluoroquinolone that possesses a broad spectrum of antibacterial activity, with extended activity against gram-positive pathogens, especially streptococci and staphylococci from patients with community-acquired infections. DC-159a showed activity against Streptococcus spp. (MIC(90), 0.

In vitro and in vivo antibacterial activities of DK-507k, a novel fluoroquinolone.

The antibacterial activities of DK-507k, a novel quinolone, were compared with those of other quinolones: ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, sitafloxacin, and garenoxacin (BMS284756). DK-507k was as active as sitafloxacin and was as active as or up to eightfold more active than gatifloxacin, moxifloxacin, and garenoxacin against Streptococcus pneumoniae, methicillin-susceptible and methicillin-resistant Staphylococcus aureus, and coagulase-negative staphylococci. DK-507k was as active as or 4-fold more active than garenoxacin and 2- to 16-fold more active than gatifloxacin and moxifloxacin against ciprofloxacin-resistant strains of S.

MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 2: achieving activity in vivo through the use of alternative scaffolds.

Problems of low solubility, high serum protein binding, and lack of efficacy in vivo in first generation MexAB-OprM specific efflux pump inhibitors were addressed. Through the use of pharmacophore modelling, the key structural elements for pump inhibition were defined. Use of alternative scaffolds upon which the key elements were arrayed gave second generation leads with greatly improved physical properties and activity in the potentiation of antibacterial quinolones (levofloxacin and sitafloxacin) versus Pseudomonas aeruginosa in vivo.