Paradoxical activity of beta-lactam antibiotics against Proteus vulgaris in experimental infection in mice.
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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)
Complete genome sequence of Streptomyces cattleya NRRL 8057, a producer of antibiotics and fluorometabolites.
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Utilization of ornithine and arginine as specific precursors of clavulanic acid.
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Ornithine and arginine (5 to 20 mM), but not glutamic acid or proline, exerted a concentration-dependent stimulatory effect on the biosynthesis of clavulanic acid in both resting-cell cultures and long-term fermentations of Streptomyces clavuligerus. Ornithine strongly inhibited cephamycin biosynthesis in the same strain. [1-14C]-, [5-14C]-, or [U-14 C] ornithine was efficiently incorporated into clavulanic acid, whereas the incorporation of uniformly labeled glutamic acid was very poor. [U-14C] citrulline were not incorporated at all. Mutant nca-1, a strain that is blocked in clavulanic acid biosynthesis, did not incorporate arginine into clavulanic acid. S. clavuligerus showed arginase activity, converting arginine into ornithine, but not amidinotransferase activity. Both arginase activity and clavulanic acid formation were enhanced simultaneously by supplementing the production medium with 10 mM arginine. (+info)
Evaluation of the bactericidal activity of beta-lactam antibiotics on slowly growing bacteria cultured in the chemostat.
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The bactericidal activity of 23 beta-lactam antibiotics was compared in slowly growing bacteria cultured in a chemostat. In an attempt to mimic possible in vivo conditions, slowly growing cultures were produced by limitation of iron, glucose, phosphate, or magnesium. Only select antibiotics remained effectively bactericidal against slowly growing cells. For these compounds, the rate of antibiotic-induced loss of viability was a constant when killing was expressed per generation (in contrast to absolute time) in that slowly growing bacteria were killed proportionately more slowly. Individual antibiotics differed greatly, however, in their specific bactericidal activities against slowly growing cells, i.e., in the absolute degree of killing elicited during exposure of the bacteria to MIC equivalents of the drugs. Specific bactericidal activities varied not only with drug structure but also with the bacterial strains and, to a lesser extent, with the nature of the growth-limiting nutrient. In slowly growing cultures exposure to the low drug concentrations studied here (near MIC) caused killing without detectable lysis. Antibiotics with high specific bactericidal activities were capable of rapidly killing cultures of slowly growing pathogens despite extremely long generation times approaching those reported for in vivo growth rates. (+info)
Antimicrobial activity of cefmetazole (CS-1170) and recommendations for susceptibility testing by disk diffusion, dilution, and anaerobic methods.
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Cefmetazole, formerly CS-1170, was found to have antimicrobial activity slightly superior to that of cefoxitin but a clinically usable antimicrobial spectrum that should be considered identical to that of cefoxitin. Disk diffusion and dilution test methods with cefmetazole correlated highly (r, greater than or equal to 0.95) with cefoxitin results. The recommended 30-micrograms cefmetazole disk interpretive breakpoints for susceptibility and resistance were greater than or equal to 18 mm (MIC, less than or equal to 8.0 micrograms/ml) and less than or equal to 14 mm (MIC, greater than or equal to 32 micrograms/ml), respectively. Cefmetazole and cefoxitin should be considered to be in the same antimicrobial spectrum class, requiring separate testing for other cephalosporins such as cephalothin, cefamandole, cefuroxime, and cefotetan. Recommended interpretive criteria performed well for fastidious organisms (Haemophilus influenzae, Neisseria meningitidis, and Branhamella catarrhalis) and for broth microdilution tests with anaerobes. Cefmetazole and cefoxitin broth disk elution tests for anaerobic bacteria produced higher rates of false susceptibility results. (+info)
Effects of 1-S replaced and/or decarboxylated latamoxef on rabbit platelet aggregation in vitro.
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Latamoxef, 1-S replaced and/or decarboxylated derivatives of latamoxef were examined for their effects on ADP-, collagen- and platelet activating factor (PAF)-induced rabbit platelet aggregation in vitro. The results were compared with those of cefotaxime, cefmetazole, carbenicillin and aspirin. Latamoxef produced a dose-dependent inhibition of platelet aggregation at concentrations over about 4 mM, and the potency was almost similar to that produced by the other beta-lactam antibiotics, although the inhibiting effect of ADP-induced aggregation was more potent for latamoxef, whereas that on collagen-induced aggregation was stronger for cefmetazole and carbenicillin. The inhibitory effect of beta-lactam antibiotics on collagen-induced aggregation was, however, much weaker than that of aspirin. With respect to drug potency, replacement of the oxygen atom in the oxacephem ring with a sulfur atom caused no significant change in ADP-induced aggregation or slightly stronger inhibition of collagen- and PAF-induced aggregations. The decarboxylated derivatives of latamoxef and the 1-S replaced analogue of latamoxef showed slightly weaker inhibition of ADP-induced aggregation, but much stronger inhibition of collagen- and PAF-induced aggregation than the parent compounds. These data suggest that 1) the oxygen atom in the oxacephem ring is not responsible for the inhibitory effect of latamoxef on platelet aggregation and 2) the carboxyl group in the amide side chain had no significant role in this inhibition. (+info)
In vitro activity of cefotetan compared with that of other antimicrobial agents against anaerobic bacteria.
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The activity of cefotetan against 430 strains of anaerobic bacteria was compared with that of cefoxitin, ceftizoxime, clindamycin, metronidazole, and chloramphenicol. Percent susceptible values for the Bacteroides fragilis group were 60, 80, 29, 86, 100, and 100%, respectively. Percent susceptible values for the B. fragilis species were 91, 92, 46, 98, 100, and 100%, respectively. Non-B. fragilis-group Bacteroides species were inhibited very well (90 to 100%) by all drugs except ceftizoxime (80%). Cefotetan and metronidazole were the most active agents against Clostridium difficile. Percent susceptible values for all strains were 72, 79, 44, 82, 93, and 98%, respectively. (+info)