cefuzonam and flomoxef

The excretion of medicated drugs into saliva may disturb the oral environment and antibiotic excretion into saliva appears to be regulated by many factors that have not been fully explored.. Excretion of four cephem antibiotics into saliva was examined in healthy volunteers and rats, using high-performance liquid chromatography, and the relationship between excretion levels and plasma protein-binding activities of the antibiotics was investigated.. Following addition of 50 microgram/ml of each antibiotic to human plasma, protein binding rates (PBRs) of cefuzonam (CZON, molecular weight (MW): 535.58), cefotaxime (CTX, MW: 477.45), flomoxef (FMOX, MW: 518.45) and cefozopran (CZOP, MW: 551.99) were 87.8 +/- 1.2, 70.8 +/- 0.8, 36.2 +/- 0.5 and 8.3 +/- 0.3%, respectively. In rat plasma, PBRs of the four antibiotics were 94.0 +/- 0.5, 62.1 +/- 1.4, 54.0 +/- 0.8 and 6.0 +/- 0.8%, respectively. Similar PBRs were observed when the antibiotic concentration was increased to 100 and 200 microgram/ml. CZOP was most rapidly excreted into saliva and had the highest concentration in saliva among the tested antibiotics, while the plateau level of CZON was the lowest. The excreted levels of each antibiotic in saliva, when locally perfused through the rat facial artery, were inversely associated with each PBR. Similarly, the ratios of antibiotic concentration in saliva to rat plasma were almost constant for each antibiotic, revealing an inverse relationship with PBRs.. These results appear to indicate that low molecular weight antibiotics are excreted into saliva through passive diffusion, inversely relating to their PBRs, and that high concentrations of antibiotics in the saliva have the potential to change the oral ecological environment.

Topics: Adult; Animals; Area Under Curve; Cefotaxime; Cefozopran; Ceftizoxime; Cephalosporins; Chromatography, High Pressure Liquid; Diffusion; Female; Humans; Hydrogen-Ion Concentration; Injections, Intravenous; Kinetics; Male; Perfusion; Protein Binding; Rats; Rats, Sprague-Dawley; Saliva; Statistics, Nonparametric

The in vitro and in vivo antibacterial activities of sulopenem (CP-70,429),a new parenteral penem antibiotic, were compared with those of imipenem (IPM), flomoxef, cefuzonam (CZON) and cefotaxime. Sulopenem possessed broad-spectrum activities against Gram-positive bacteria and Gram-negative bacteria. Antibacterial activities of sulopenem against methicillin-sensitive Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pyogenes and Streptococcus pneumoniae were equivalent to or somewhat superior to those of IPM. Against members of the family Enterobacteriaceae, sulopenem was 4- to 260-fold more active than reference antibiotics with broad-spectra. In a killing kinetics study for Haemophilus influenzae, sulopenem showed a 99.9% decrease of viable cells after 8 hours at a concentration of 0.20 micrograms/ml. This effect was obtained at a concentration 8-fold lower than that of IPM. The protective effects of sulopenem in murine experimental systemic infections were superior to those of imipenem/cilastatin. In murine experimental mixed infection with Escherichia coli and Bacteroides fragilis, sulopenem had lower ED50, in other words stronger antimicrobial activities than IPM. The therapeutic effect of sulopenem are related well with its MIC value. In guinea pigs experimental lung infection with Klebsiella pneumoniae, sulopenem was more effective than CZON or cefotiam.

Topics: Animals; Anti-Bacterial Agents; Bacteroides fragilis; Bacteroides Infections; beta-Lactam Resistance; Cefotaxime; Ceftizoxime; Cephalosporins; Escherichia coli Infections; Gram-Negative Bacteria; Gram-Positive Bacteria; Guinea Pigs; Imipenem; Klebsiella Infections; Lactams; Lung Diseases; Mice; Mice, Inbred ICR; Thienamycins

We determined the in vitro activities of arbekacin in combination with other antibiotics against 96 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). Efficacies were evaluated by comparing frequencies of susceptible strains at concentrations of antibiotics present in serum 3 hours after intravenous administration of recommended dosages with those obtained with addition of 1 or 2 micrograms/ml of arbekacin. The addition of arbekacin significantly increased the antibacterial activities of cefotiam, cefuzonam, flomoxef and fosfomycin, but had no effect on the activity of either imipenem or minocycline. Arbekacin in combination with fosfomycin was found to have the greatest activity against MRSA among combinations tested. In addition, arbekacin had excellent antimicrobial activity against Pseudomonas aeruginosa, compared to other anti-pseudomonal agents such as piperacillin, ceftazidime and imipenem.

Topics: Aminoglycosides; Anti-Bacterial Agents; Cefotiam; Ceftizoxime; Cephalosporins; Dibekacin; Drug Therapy, Combination; Fosfomycin; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Staphylococcus aureus

We evaluated combined effects of sulbactam/cefoperazone (SBT/CPZ) with each of imipenem/cilastatin (IPM), cefuzonam, flomoxef, amikacin (AMK) and tobramycin (TOB) against 324 clinical strains. Through this study, we obtained the following results. 1. Against Serratia marcescens and Enterobacter cloacae, good synergism was obtained by combining SBT/CPZ with IPM, AMK, or TOB. 2. Against Pseudomonas aeruginosa, good synergism was obtained by combining SBT/CPZ with AMK or TOB. 3. When SBT/CPZ was used in combination with IPM, antagonism was observed among about 45% of strains of P. aeruginosa.

Topics: Amikacin; Anti-Bacterial Agents; Bacteria; Cefoperazone; Ceftizoxime; Cephalosporins; Cilastatin; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Humans; Imipenem; Sulbactam; Tobramycin

The synthesis and antibacterial activity of 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2-(hydroxy or alkoxy)iminoacetamido]cephalosporins with various thiadiazolylthiomethyl moieties at the 3-position are discussed. Of the compounds (1a-1e, 7a-7d), 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2-hydroxyiminoacetamido]-3-[(1,2 ,4- thiadiazol-5-yl)thiomethyl]cephalosporin (1d: FK312) exhibited the highest activity against Gram-positive and Gram-negative bacteria, especially, against methicillin-resistant Staphylococcus aureus. Furthermore, the pharmacokinetic profiles of the compound 1d showed longer serum levels than that of ceftriaxone in rats.

Topics: Anti-Bacterial Agents; Ceftizoxime; Cephalosporins; Microbial Sensitivity Tests; Staphylococcus aureus; Structure-Activity Relationship

The influence of Mueller-Hinton (MH) broth (from BBL Microbiology Systems, and Difco Laboratories) of minimum inhibitory concentrations (MIC) of cefuzoname (CZON), flomoxef (FMOX), imipenem (IPM), and minocycline (MINO) for 100 strains of Staphylococcus aureus was investigated. Antibacterial activity of MINO was stronger than any other antibiotics. MICs of CZON for 16 strains (14 of 50 methicillin-resistant S. aureus (MRSA), 2 of 50 methicillin-sensitive S. aureus) were greater than or equal to 4-fold greater when tested in BBL MH broth than when tested in Difco MH broth, thus, different media altered categories of some strains (8 of 50 MRSA) from susceptible to resistant. MICs of FMOX in the BBL MH broth for 12 of 50 MRSA strains rose greater than or equal to 4-fold compared to the Difco MH broth. On the other hand, MICs of IPM and MINO were affected very little by the different brand of MH broth used.

Topics: Ceftizoxime; Cephalosporins; Culture Media; Drug Resistance, Microbial; Imipenem; Minocycline; Staphylococcus aureus; Tetracyclines