Levels of cefmenoxime in sera and peritoneal tissues of patients undergoing gastrointestinal surgery. (1/55)

It is not known whether a prophylactic antibiotic administered prior to surgery reaches adequate levels in the peritoneum, where peritonitis may take place. This study determined levels of cefmenoxime in sera and peritoneal tissues of patients undergoing gastrointestinal surgery. Fifteen patients who underwent elective gastrointestinal surgery received an intravenous drip infusion of cefmenoxime (2 g) over 1 h prior to surgery. In patients who underwent gastrectomy, the level of cefmenoxime in serum was 130.8 +/- 6.9 micrograms/ml at laparatomy and decreased to 5.0 +/- 0.7 micrograms/ml at 4 h. Levels in parietal peritoneal and omental tissues at laparotomy were 35.3 +/- 5.2 and 19.2 +/- 3.5 micrograms, respectively, and decreased time dependently. In patients who underwent cholecystectomy, the level of cefmenoxime in serum was 137.9 +/- 7.3 micrograms/ml at laparotomy and decreased to 5.0 +/- 1.2 micrograms/ml at 4 h. Levels in parietal peritoneal and omental tissues were 31.0 +/- 8.4 and 13.7 +/- 3.3 micrograms/g, respectively, and decreased time dependently. The level of cefmenoxime in serum correlated with the levels of cefmenoxime in parietal peritoneum (r = 0.64, P less than 0.01) and in omentum (r = 0.47, P less than 0.02). In patients with appendicitis who received a bolus injection of 2 g of cefmenoxime, the level of drug in inflammatory omental tissue correlated with the level in serum. The levels in peritoneal tissue during surgery lasting up to 2 h were significantly greater than in MIC of cefmenoxime against almost all bacteria reported. A preoperative single dose of 2 g of cefmenoxime probably is effective as a prophylactic for intraoperative contamination.  (+info)

Synergistic effects of romurtide and cefmenoxime against experimental Klebsiella pneumonia in mice. (2/55)

We investigated the synergistic effects of romurtide (MDP-Lys [L18]) and cefmenoxime (CMX) in the treatment of experimental Klebsiella pneumonia in mice. Mice were infected with 1 x 10(4) CFU of Klebsiella pneumoniae by inhalation of aerosol bacterial suspension. About 90% of untreated animals died within a week; however, the mortality rate of animals treated with CMX alone at a dose of 40 mg/kg/day was 60% at 7 days after the infection. When one or two doses of L18 were administered before or after the infection concomitantly with CMX, a remarkable improvement in the survival rate was observed. There was no significant improvement in the survival rate of animals treated with L18 alone before or after infection. Histopathological sections of the lungs of mice treated with CMX and L18 showed slower progression of infection than those of mice treated with CMX alone. Significant differences were also found in quantitative cultures of viable bacteria in the lungs 1 to 4 days after the infection. Although viable bacterial counts in the lungs of the control and CMX-treated groups showed a rapid increase 24 to 48 h after the infection, they remained lower than the initial counts (x 10(4)) in the lungs of mice treated with combination regimens. From these results, it can be concluded that L18 is a useful biological response modifier in the treatment of acute pulmonary bacterial infections.  (+info)

Studies on condensed-heterocyclic azolium cephalosporins. III. Synthesis and antibacterial activity of 7 beta-[2-(2-amino-5-substituted-thiazol-4-yl)-2 (Z)-alkoxyiminoacetamido]-3-(condensed-heterocyclic azolium)methyl-3-cephem-4- carboxylates. (3/55)

As a part of our research on the synthesis of cephalosporins bearing condensed-heterocyclic azolium groups at the 3 position in the cephalosporin nucleus, we describe herein the synthesis of 7 beta-[2-(2-amino-5-halogeno-, methylthio-, methylsulfinyl-, methylsulfonyl- and sulfothiazol-4-yl)-2(Z)-alkoxyiminoacetamido] cephalosporins and their antibacterial activity. Among the compounds prepared, 7 beta-[2-(2-amino-5-chlorothiazol-4-yl)-2(Z)- methoxyiminoacetamido]-3-(imidazo[1,5-a]-pyridinium-1-yl)methyl-3-cephem -4-carboxylate (14) showed good antibacterial activity against both Staphylococcus aureus including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, whereas the antibacterial activity against other Gram-negative bacteria was a slightly lower than that of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3-(im ida zo [1,2-a]pyridinium (I-1) and imidazo[1,5-a]pyridinium (I-4)-1-yl)methyl-3-cephem-4-carboxylates.  (+info)

Application of mathematical model to multiple-dose experimental chemotherapy for fatal murine pneumonia. (4/55)

Two beta-lactam antibiotics, cefazolin and cefmenoxime, were administered for 7 days to mice with pneumonia caused by Klebsiella pneumoniae by using dosage regimens that would simulate multiple dosing in usual clinical treatments at dosing intervals of 8 or 12 h. Viable numbers of the bacteria in the lungs were measured at 12- or 24-h intervals. The mathematical model established in a previous single-dose study was applied in this study to explain the time courses of the changes in bacterial count over 7 days. However, because the error in viable count measurements was larger than that in the previous study, the time course of the changes in mean viable count was not regular and the viable count reduction rate changed during multiple dosing, and therefore it was difficult to explain the time course by repeated application of the mathematical model described previously. This study suggests that the changes in pharmacokinetic and pharmacodynamic parameters during multiple dosing need to be considered.  (+info)

Paradoxical activity of beta-lactam antibiotics against Proteus vulgaris in experimental infection in mice. (5/55)

In previous papers (Y. Ikeda and T. Nishino, Antimicrob. Agents Chemother. 32:1073-1077, 1988; Y. Ikeda, T. Nishino, and T. Tanino, Antimicrob. Agents Chemother. 31:865-869, 1987), we reported that many of the 7-aminothiazolyl cephalosporins, such as cefmenoxime, showed paradoxically reduced activity against Proteus vulgaris at higher concentrations, whereas these paradoxical effects were not observed for other types of cephalosporins, such as cefbuperazone and cefoperazone. In this study, we compare the therapeutic effect of cefmenoxime with that of cefbuperazone and explore the in vivo paradoxical effect of cefmenoxime by using an experimental infection model in mice. In an intraperitoneal infection with P. vulgaris 11, the survival rate with cefmenoxime was increased to 43% at 3.13 mg/kg but was lower at higher doses. On the other hand, cefbuperazone did not show such a paradoxical therapeutic effect. In mice infected with P. vulgaris 11, cefmenoxime levels in both serum and peritoneal washings were rapidly reduced and beta-lactamase activities in the peritoneal cavity were increased at higher cefmenoxime doses. These findings suggested that high levels of cefmenoxime at the infection site induced increased production of beta-lactamase, which then rapidly inactivated the antibiotic. We conclude that the paradoxical therapeutic effect of cefmenoxime against P. vulgaris occurs by the same mechanisms as the in vitro effect and that the high beta-lactamase inducibility and low beta-lactamase stability may account for the paradoxical therapeutic effect of cefmenoxime against P. vulgaris.  (+info)

Application of mathematical model to experimental chemotherapy of fatal murine pneumonia. (6/55)

Two beta-lactam antibiotics, cefazolin and cefmenoxime, were administered in an experimental model of murine pneumonia caused by Klebsiella pneumoniae in a way which enabled us to approximate the serum antibiotic concentration time course in humans. Bacterial counts during the experiments were subjected to nonlinear least-squares analyses by using a mathematical model that explained the bacterial killing by the antibiotic concentration time course and other factors associated with antimicrobial potency and bacterial growth. Cefazolin gave a killing curve that changed synchronously with the drug levels in serum; in contrast, cefmenoxime gave a curve that was prolonged as compared with the change in the drug levels in serum. Multiple correlation coefficients were about 0.9, and the model worked well for bacterial count data. Parameters relating to antimicrobial potency of the drugs, bacterial growth rate, and drug distribution into the tissue were estimated numerically.  (+info)

In vitro assessment of the cytotoxicity of six topical antibiotics to four cultured ocular surface cell lines. (7/55)

To determine the cytotoxicity of antibiotic eyedrops to ocular surface cells using a semi-quantitative method, a range of commercially available antibiotic eyedrops were assessed by using three corneal cell lines and one conjunctival cell line. All antibiotic solutions were free of benzalkonium chloride. Cell viability was determined by the MTT assay and neutral red assay following the exposure of cells to the undiluted, 2- and 10-fold diluted drugs for 10, 30, and 60 min. Toxicity was compared using % cell viability score (%CVS) . The tested eyedrops and values of %CVS50 and %CVS40/80 were Bestron((R)) (cefmenoxime, 100, 94) , Panimycin((R)) (dibekacin, 86, 58) , Noflo((R)) (norfloxacin, 90, 50) , Cravit((R)) (levofloxacin, 86, 46) , Tosfulo((R)) (tosufloxacin, 57, -3) , and Vigamox((R)) (moxifloxacin, 57, -6) . Cell viability markedly increased after dilution. For instance, cell viability assayed by MTT was > 80% for all the measurements in antibiotics diluted 10-fold, and the rate of the measurements showing > 80% cell viability decreased to 43% (31 out of 72 measurements) in the solutions diluted 2-fold. Of the drugs tested, Bestron((R)) containing cefmenoxime showed the weakest toxicity. Vigamox((R)) containing moxifloxacin and Tosuflo((R)) containing tosufloxacin were more toxic when compared with the other antibiotics. CVS was useful for the comparison of the cytotoxicity of the drugs.  (+info)

Antimicrobial activity and stability to beta-lactamase of BMY-28271, a new oral cephalosporin ester. (8/55)

BMY-28271, the acetoxyethyl ester of BMY-28232, 7-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3(Z) -propen-1-yl-3- cephem-4-carboxylic acid, is a new oral cephalosporin. BMY-28232 has a widely expanded spectrum with high activity against gram-positive and gram-negative bacteria. BMY-28232 is far more active than cefixime or cefteram against Staphylococcus aureus and Staphylococcus epidermidis. Against gram-negative bacteria, the activity of BMY-28232 was comparable to or somewhat weaker than that of cefixime or cefteram. BMY-28232 was a poor substrate for various beta-lactamases. Orally administered BMY-28271 had a good therapeutic effect on systemic infections with S. aureus and some gram-negative bacteria in mice. Oral BMY-28271 was efficacious against S. aureus Smith infection: the efficacy of BMY-28271 was 80 to 90 times higher than that of cefixime or cefteram.  (+info)

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