Potent oxazolidinone antibacterials with heteroaromatic C-ring substructure.

Novel oxazolidinone analogues bearing a condensed heteroaromatic ring as the C-ring substructure were synthesized as candidate antibacterial agents. Analogues 16 and 21 bearing imidazo[1,2-a]pyridine and 18 and 23 bearing [1,2,4]triazolo[1,5-a]pyridine as the C-ring had excellent in vitro antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis (VRE), and penicillin-resistant Streptococcus pneumoniae (PRSP). They also showed promising therapeutic effects in a mouse model of lethal infection.

Unique profiles of changes in cell membrane fluidity during ethanol-induced yeast-to-pseudohyphal transition in Candida tropicalis.

A dimorphic transition from the yeast form to filamentous one in Candida tropicalis pK233 is triggered by the addition of ethanol into the glucose semi-defined liquid medium and the process of filamentation accompanies temporal depolarization of yeast cells. The transition is completely prevented by further supplementation of myo-inositol at the start of cultivation. The addition of ethanol caused an increase in membrane fluidity during the process of depolarization, and then fluidity was gradually lowered to the level equivalent with that of the stationary-phase yeast cells in accordance with filamentation.

In vitro antibacterial activities of S-013420, a novel bicyclolide, against respiratory tract pathogens.

Objectives: The in vitro activity of S-013420, a novel bicyclolide, was investigated.

Methods: All test strains for this study were isolated from Japanese medical facilities. MICs were determined by the microbroth dilution method or agar dilution method according to the CLSI guidelines.

Susceptibility of Pseudomonas aeruginosa clinical isolates in Japan to doripenem and other antipseudomonal agents.

We investigated the susceptibility of 694 Pseudomonas aeruginosa clinical isolates to nine antipseudomonal agents including doripenem. Test strains were collected from 23 Japanese medical facilities from 1992 to 2004. Doripenem showed a minimum inhibitory concentration for 90% of the organisms (MIC(90)) of 8 microg/mL, which was the lowest among the tested antipseudomonal agents.

Staphylococcus aureus clinical isolate with high-level methicillin resistance with an lytH mutation caused by IS1182 insertion.

We previously reported that deficiency of the lytH gene, whose product is homologous to lytic enzymes, caused the elevation of methicillin resistance in Staphylococcus aureus strain SR17238, a strain of S. aureus with a low level of resistance to methicillin (low-level MRSA) (J. Bacteriol.

[Susceptibility of clinical isolates from primary care clinics to oral antibacterial agents].

The antimicrobial susceptibility of clinical isolates from specimens of patients in primary care clinics in 2005 was investigated by determining the minimum inhibitory concentrations of oral antibacterial agents. The numbers of test strains were 550 for Gram-positive aerobes, 700 for Gram-negative aerobes, and 150 for anaerobes. Cefcapene (CFPN), cefditoren (CDTR), and cefteram (CFTM) showed the most potent activities against Staphylococcus spp.

Occurrence of PER-1 producing clinical isolates of Pseudomonas aeruginosa in Japan and their susceptibility to doripenem.

The acquisition of resistance by extended-spectrum beta-lactamases (ESBL) has been reported primarily for Enterobacteriaceae, but there are few reports on the isolation of ESBL-producing Pseudomonas aeruginosa. PER-1-type ESBL producing P aeruginosa has been found in various regions around the world but there are no reports of clinical isolates in Japan. During our susceptibility surveillance studies over a 10 year period, we found four clinical isolates resistant to ceftazidime due to production of PER-1.

Ethanol-induced pseudohyphal transition in the cells of Candida tropicalis: participation of phosphoinositide signal transduction.

Ethanol-induced pseudohyphal development in the cells of Candida tropicalis Pk233 was accompanied by the transient accumulation of inositol 1,4,5-trisphosphate (IP3) that occurred at an early growth stage. The concomitant addition of myo-inositol prevented the activation of IP3 accumulation and cancelled pseudohyphal development in the presence of ethanol. The addition of a specific phospholipase C inhibitor, U73 122, inhibited ethanol-induced pseudohyphal transition at the concentrations of subinhibitory levels of cell growth.

In vitro activity of S-3578, a new broad-spectrum cephalosporin active against methicillin-resistant staphylococci.

The in vitro antibacterial activity of S-3578, a new parenteral cephalosporin, against clinical isolates was evaluated. The MICs of the drug at which 90% of the isolates were inhibited were 4 micro g/ml for methicillin-resistant Staphylococcus aureus (MRSA) and 2 micro g/ml for methicillin-resistant Staphylococcus epidermidis, which were fourfold higher than and equal to those of vancomycin, respectively. The anti-MRSA activity of S-3578 was considered to be due to its high affinity for penicillin-binding protein 2a (50% inhibitory concentration, 4.