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S Mitsuhashi

Publications and source records attributed to S Mitsuhashi.

At least 109 records · Page 6Linked to original sources
PubMed1989

In vitro and in vivo antibacterial activities of KB-5246, a new tetracyclic quinolone.

The in vitro and in vivo antibacterial activities of KB-5246, a tetracyclic quinolone, were compared with those of ciprofloxacin, ofloxacin, and norfloxacin. KB-5246 demonstrated a broad antibacterial spectrum. The in vitro activity of KB-5246 against gram-negative bacteria was higher than that of ofloxacin or norfloxacin and was comparable to that of ciprofloxacin. KB-5246 demonstrated the greatest activity against gram-positive bacteria of the four agents tested. Among Streptococcus pyogenes strains resistant to 1.56 micrograms of norfloxacin per ml, there were 26 strains susceptible to 0.2 micrograms of KB-5246 per ml. Similarly, among the Staphylococcus aureus and Staphylococcus epidermidis strains resistant to 3.13 micrograms of norfloxacin per ml, there were 23 S. aureus and 11 S. epidermidis strains susceptible to 0.39 micrograms of KB-5246 per ml. Among the Streptococcus pneumoniae and Enterococcus faecalis strains resistant to 12.5 micrograms of norfloxacin per ml, there were 5 S. pneumoniae and 10 E. faecalis strains susceptible to 0.39 micrograms of KB-5246 per ml. KB-5246 had bactericidal activity at the MIC. KB-5246 demonstrated excellent antibacterial activity against various systemic infections in mice. After oral administration, KB-5246 was as active as ofloxacin and about two times more active than norfloxacin.

Animals↗
PubMed1989

In vitro activity of AT-4140 against clinical bacterial isolates.

The activity of AT-4140, a new fluoroquinolone, was evaluated against a wide range of clinical bacterial isolates and compared with those of existing analogs. AT-4140 had a broad spectrum and a potent activity against gram-positive and -negative bacteria, including Legionella spp. and Bacteroides fragilis. The activity of AT-4140 against gram-positive and -negative cocci, including Acinetobacter calcoaceticus, was higher than those of ciprofloxacin, ofloxacin, and norfloxacin. Its activity against gram-negative rods was generally comparable to that of ciprofloxacin. Some isolates of methicillin-resistant Staphylococcus aureus (MIC of methicillin, greater than or equal to 12.5 micrograms/ml) were resistant to existing quinolones, but many of them were still susceptible to AT-4140 at concentrations below 0.39 micrograms/ml. The MICs of AT-4140, ciprofloxacin, ofloxacin, and norfloxacin for 90% of clinical isolates of methicillin-resistant S. aureus were 0.2, 12.5, 6.25, and 100 micrograms/ml, respectively. AT-4140 was bactericidal for each of 20 clinical isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa at concentrations near the MICs. AT-4140 inhibited the supercoiling activity of DNA gyrase from E. coli.

4-Quinolones↗
PubMed1989

Interaction of E1040 with cephalosporinase from Citrobacter freundii GN7391.

The interactions of E1040 with cephalosporinase from Citrobacter freundii, including affinity and hydrolysis, were studied in comparison with those of cefotaxime and ceftazidime. E1040 showed a higher stability at low drug concentrations and a much lower affinity for the enzyme than did cefotaxime or ceftazidime. These enzymological properties explain the high activity of E1040 against cephalosporinase-producing C. freundii.

Cefotaxime↗
PubMed1989

Effects of beta-lactamases and omp mutation on susceptibility to beta-lactam antibiotics in Escherichia coli.

Four types of beta-lactamases consisting of a penicillinase type I (TEM-1), a penicillinase type II (OXA-1), a cephalosporinase of Citrobacter freundii, and a cephalosporinase of Proteus vulgaris were introduced into Escherichia coli MC4100 and its omp mutants, MH1160 (MC4100 ompR1) and MH760 (MC4100 ompR2), by transformation. Effects of the combination of the omp mutations and these beta-lactamases on the susceptibility of E. coli strains were studied with 15 beta-lactam antibiotics including cephalosporins, cephamycins, penicillins, imipenem, and aztreonam. The ompR1 mutant, MH1160, lacks OmpF and OmpC, and it showed reduced susceptibility to 11 of the 15 beta-lactam agents. The reduction in susceptibility to cefoxitin, moxalactam, and flomoxef was much greater than reduction in susceptibility to the other agents. When the ompR1 mutant produced the cephalosporinase of C. freundii, the susceptibility of the mutant to 12 of the 15 beta-lactam antibiotics decreased. The reduction in susceptibility of MH1160 to 10 of the 12 agents affected by the enzyme was two- to fourfold greater than that observed in MC4100. Such a synergistic effect was also observed with the cephalosporinase of P. vulgaris and ompR1 mutation against six cephalosporins, moxalactam, and aztreonam.

Anti-Bacterial Agents↗
PubMed1989

Interaction of cefpirome and a cephalosporinase from Citrobacter freundii GN7391.

The interaction of cefpirome and a cephalosporinase from Citrobacter freundii, including hydrolysis and inhibition, was studied in comparison with those of cefotiam, cefotaxime, and ceftazidime. Cefpirome was hydrolyzed by the enzyme more rapidly at Vmax than were cefotaxime and ceftazidime. However, the low affinity of the enzyme for cefpirome caused a reduction in the hydrolytic rate of cefpirome at a low drug concentration (0.1 microM). The high stability of cefpirome at a low concentration explains the high antimicrobial activity of the agent against cephalosporinase-producing bacteria.

Cefotaxime↗
PubMed1989

Quinolone resistance in clinical isolates of Serratia marcescens.

The uptakes of norfloxacin by quinolone-resistant and -susceptible strains of Serratia marcescens were almost the same and 50% inhibitory concentrations for DNA gyrase and the MICs of quinolones were correlated, suggesting that DNA gyrase alterations are the basis of quinolone resistance.

Anti-Infective Agents↗
PubMed1989

[Analysis of patients surviving for six months after irradiation of a bone metastasis].

The effects of treatment of a bone metastasis have been studied in 49 patients who survived for more than six months after radiotherapy (RT). Relief from the symptoms reached a rate as high as 91% (85/93 irradiated sites) irrespective of the primary site of the cancer. However, the survival rate and the rate of symptom relief maintenance were statistically higher in those with breast cancer (15 patients, 38 irradiated sites) than in those with a lung cancer (15, 24). The local control rate was dose dependent (TDF). High-dose irradiation, therefore is recommended to achieve a high local control rate for patients with a long life expectancy.

Bone Neoplasms↗
PubMed1989

Comparison of the in vitro and in vivo antibacterial activities of cefepime (BMY-28142) with ceftazidime, cefuzonam, cefotaxime and cefmenoxime.

Cefepime (BMY-28142), a new semisynthetic cephalosporin, was evaluated for in vitro and in vivo antibacterial activities in comparison with ceftazidime, cefuzonam, cefotaxime and cefmenoxime. Cefepime showed a well-balanced, broad spectrum of activity against a number of clinical isolates collected in Japan. The activity of cefepime against Gram-positive bacteria was several times greater than that of ceftazidime, nearly comparable to cefotaxime and cefmenoxime, and slightly weaker than cefuzonam. Against Enterobacteriaceae, cefepime showed superior activity to the reference cephalosporins against Proteus inconstans, Providencia rettgeri, Morganella morganii, Citrobacter freundii and Enterobacter cloacae. The activity of cefepime against Pseudomonas aeruginosa was nearly comparable to that of ceftazidime. Cefotaxime, cefuzonam and cefmenoxime were substantially less active against P. aeruginosa. Cefepime was more stable than cefuzonam, cefotaxime and cefmenoxime to various types of beta-lactamases from Gram-negative bacteria. The high in vitro activity of cefepime was reflected in its in vivo efficacy against experimental infections in normal and immuno-suppressed mice. Cefepime was the most effective among the cephalosporins tested against four Gram-negative bacterial infections.

Animals↗
PubMed1989

In vitro and in vivo antibacterial activity of the new semisynthetic cephalosporin cefpirome.

Cefpirome (HR 810), a new semisynthetic cephalosporin derivative, was found to have a broad antibacterial spectrum against gram-positive and gram-negative bacteria. Against Staphylococcus aureus, cefpirome was more active than not only cefotaxime and ceftazidime but also cefotiam. Against gram-negative bacteria, especially, Enterobacter cloacae and Citrobacter freundii, it was also more active than the other antibiotics tested, but against Pseudomonas aeruginosa, it was less active than ceftazidime. Cefpirome was stable to hydrolysis by the common plasmid mediated beta-lactamases and was stable to the action of chromosomal cephalosporinases. But it was slightly hydrolyzed by both Rms 213 mediated penicillinase and oxyiminocephalosporinases produced by Proteus vulgaris and Pseudomonas cepacia. When cefpirome was administered subcutaneously to mice experimentally infected with Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae or Pseudomonas aeruginosa, its efficacy well reflected its in vitro potency.

Animals↗
PubMed1988

In-vitro and in-vivo antibacterial activity of fleroxacin, a new fluorinated quinolone.

The in-vitro and in-vivo antibacterial activities of fleroxacin were compared with those of other new quinolones including NY-198. Fleroxacin showed potent activity against most members of the Enterobacteriaceae, Neisseria gonorrhoeae and Haemophilus influenzae, and good activity against Pseudomonas aeruginosa and staphylococci. Against these bacteria, the activity of fleroxacin was roughly comparable to that of norfloxacin, enoxacin, NY-198, and ofloxacin, but slightly less than that of ciprofloxacin. Fleroxacin strongly inhibited DNA supercoiling activity of DNA gyrase purified from Escherichia coli which may explain its high antibacterial activity. The protective effects of a single oral dose of fleroxacin in mice were greater than those of norfloxacin and comparable to or greater than that of ciprofloxacin, ofloxacin and NY-198 against systemic infections with Staphylococcus aureus, Esch. coli and Ps. aeruginosa, and Serratia marcescens.

Anti-Infective Agents↗
PubMed1988

Purification and some properties of a chloramphenicol acetyltransferase mediated by plasmids from Vibrio anguillarum.

Vibrio anguillarum strains were isolated from chloramphenicol-resistant bacteria in diseased fish. Plasmid Rms418, which confers chloramphenicol resistance, was transferred from V. anguillarum GN11379 to Escherichia coli K12 by conjugation. The Rms418-encoded chloramphenicol acetyltransferase (CAT) [EC 2.3.1.99] was isolated and purified to homogeneity using affinity chromatography on immobilized p-amino-chloramphenicol or ATP. The general CAT could be adsorbed by a matrix with a chloramphenicol base ligand (Zaidenzaig, Y. & Shaw, W.V. (1976) FEBS Lett. 62,266-271), but the Rms418-encoded CAT was not bound under these conditions. The specific activity of the enzyme, when measured by the spectrophotometric assay, was 71.4 units/mg protein at 37 degrees C. The molecular weight of the enzyme treated with SDS and 2-mercaptoethanol was shown to be approximately 22,000. The molecular weight of the native enzyme, as determined by gel filtration, was approximately 69,000, and the optimal pH was 7.8. The Km values for chloramphenicol and CoASAc were 34.5 and 150 microM, respectively. Enzyme activity was inhibited by HgCl2, p-chloromercuribenzoate (p-CMB), 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), and ethylendiaminotetraacetic acid (EDTA). The half life at 53 degrees C was approximately 100 min.

Cations, Divalent↗
PubMed1988

Purification of Citrobacter freundii DNA gyrase and inhibition by quinolones.

DNA gyrase is a bacterial enzyme which catalyzes the ATP-dependent negative supercoiling of DNA. It is the accepted target of quinolones. The enzyme from Citrobacter freundii IID976 was purified by affinity chromatography on novobiocin-Sepharose and heparin-Sepharose. It had two subunits, designated A and B, which closely resembled those of the enzyme from Escherichia coli and Micrococcus luteus in enzymatic requirements. The inhibitory effects of the quinolones on the supercoiling activities of the enzyme correlated with their antibacterial activities. New quinolones were better inhibitors of DNA gyrase than nalidixic acid and pipemidic acid. We also purified DNA gyrase from a spontaneous nalidixic acid-resistant mutant (M2-5). The gyrases from IID976 and M2-5 were defined as mixtures of subunits As+Bs (s, susceptible) and Ar+Br (r, resistant), respectively. The supercoiling activities of reconstituted Ar+Br and Ar+Bs were more resistant to quinolones than As+Bs and As+Br. These findings indicate that one mechanism of C. freundii resistance against quinolones is resistance modification of the A subunit protein.

Anti-Bacterial Agents↗
PubMed1988

Mechanism of action of cephalosporins and resistance caused by decreased affinity for penicillin-binding proteins in Bacteroides fragilis.

The susceptibilities of 52 clinical isolates of Bacteroides fragilis to five monoanionic cephalosporins were examined. Cefoperazone showed the highest antibacterial activity, followed by ceftezole, cefazolin, cefamandole, and cephalothin. There were two groups of resistant strains: one group (ca. 15%), of which B. fragilis G-232 was a typical sample, was resistant to ceftezole (MIC, 100 micrograms/ml), cefazolin (MIC, 100 micrograms/ml), and cephalothin (MIC, 200 micrograms/ml) but not cefoperazone (MIC, 6.25 micrograms/ml) or cefamandole (MIC, 25 micrograms/ml). On the basis of studies of stability to beta-lactamase, outer membrane permeation, and affinity for penicillin-binding proteins (PBPs), we conclude that decreased affinity for PBP 3 may play an important role in the resistance to ceftezole, cefazolin, and cephalothin in B. fragilis G-232. Another group (also ca. 15%), of which B. fragilis G-242 was a representative, was resistant to all five cephalosporins (MIC, 100 to 400 micrograms/ml) and produced a high amount of beta-lactamase. Similar broad-spectrum resistance was seen in a mutant of strain G-232 that had a greater-than-30-fold increase in beta-lactamase production.

Bacterial Proteins↗
PubMed1988

Purification and characterization of human renal dehydropeptidase I.

Dehydropeptidase I from human kidney was purified over 100-fold. The purified enzyme had an isoelectric point of 4.75, apparent molecular weights of 135,000 by gel filtration and of 66,500 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and an optimal pH of 7.4. Human renal dehydropeptidase I hydrolyzed imipenem, carpetimycins A and B, and Sch 29,482.

Anti-Bacterial Agents↗
PubMed1988

In vitro and in vivo antibacterial activities of T-3262, a new fluoroquinolone.

T-3262, a new fluoroquinolone, showed a broad spectrum of activity against gram-positive and gram-negative bacteria. T-3262 had most potent activity against gram-positive cocci, such as Staphylococcus, Streptococcus, and Enterococcus spp. The MICs of T-3262 for 90% of strains tested were between 0.05 and 1.56 micrograms/ml. Against members of the family Enterobacteriaceae and Pseudomonas aeruginosa, the activities of T-3262 were almost equal to those of ciprofloxacin. Obligate anaerobes were also susceptible to T-3262. T-3262 was bactericidal for one strain each of Staphylococcus aureus, Escherichia coli, and P. aeruginosa at concentrations near its MIC; and fluoroquinolones, including T-3262, inhibited DNA gyrase activity at low concentrations. The 50% effective dose of T-3262 after oral administration against systemic infections with S. aureus in mice was about 6 times lower than that of ofloxacin and about 20 times lower than that of norfloxacin.

Animals↗
PubMed1988

Clinical isolate of Citrobacter freundii highly resistant to new quinolones.

About 30% of 150 recent clinical isolates of Citrobacter freundii were resistant to greater than or equal to 3.13 micrograms of norfloxacin and ofloxacin per ml. Study of one quinolone-resistant strain for which the norfloxacin MIC was 100 micrograms/ml suggested that resistance was associated with both an altered A subunit of DNA gyrase and reduction in drug uptake accompanied by a decrease in an outer membrane protein.

Bacterial Outer Membrane Proteins↗