| The antibacterial activity of fluoroquinolones against Staphylococcus aureus 25923and Escherichia coli 25922 in vitro were stodied. At the same time, the post-antibioticeffects (PAE ) and post-antibiotic Sub-MIC effects (PA-SME) offluoroquionlones againsttwo bacteria strains were observed. The infected tissue cage models that had been improvedwere built in rabbits by implanting plastic tissue cages for studying -the PAE ofdanofloxacin against StaPhylococcus aureus and Escherichia coli in vivo. ThemorPhologica1 and ultra-strUctural changes of tWo strains exposed to danofloxacin in highand Sub-inhibitory concentrations were observed with transmission electronic microscope.The DNA gyrase of Escherichia coli were purified by novobiocin-Sepharose CL-6B, andthe activity of enzyme and the 50% inhibitory concentrations (IC,,) of danofloxacin weredetected.The PAE and PA-SME of fluoroquionlones against two bacteria strains weredetermined. DiIuting method was used fOr the drugs removaI and the growth of bacteriawas monitored by Muelle-Hinton (MH ) agar colony counting method in the study. Resultsshowed that the minimal inhibitory concentrations (MIC ) of four in five fluoroquinolones(ciprofloxacin, ofloxacin, enrofloxacin, danofloxacin and saIafloxacin ) were under 0.25u g/ml, the minimal bactercidal concentration(MBC )were under l .0 u g/ml, and the valuesof MBC/MIC were 2~4. It appeared that the fluoroquinolones had not only stronginhibitory activities, but also had quick killing activities.The results of PAE and PA-SME showed that there have long period persistentsuppression of bacterial groWth after a limited exposure to fluoroquinolones. The longestPAE of ciprofloxacin, ofloxacin, enrofloxacin, danofloxacin and salafloxacin againstStaphylococcus aureus are 3.58, 2.22, 3.22, 2.82 and 2.55 hours, respectively. The valuesagainst Escherichia coli are 4. l l, 2.76. 4.24. 4.5l and 2.88 hours, respectively. The va1uesof PAE increased as increasing of drug concentration in l~4MIC, and the period ofexposing to drugs and the quantities of inoculum also affected the PAE. The PA-SMEvalues of fluoroquinplones were longer than that of PAE in the same inducementconcentration.32002.5The infected tissue cage model in rabbits with normal host defending mechanism had been set up successfully using subcutaneously two plastic tissue cages implanted in each animal. The improved model exposing to drugs in vivo were adopted for determining PAE of danofloxacin against Staphylococcus aureus and Escherichia coli after exposed to drug for 1 hour. The PAE of danofloxacin against Staphylococcus and Escherichia were 3.41 and 4.86 hours, respectively. The long period of PAE in vitro and in vivo of danofloxacin showed that the projection of administration in clinic should been improved. It was that the interval of administration should equal the sum of the period of drug concentration in blood over MIC and the period of PAE.The morphological and ultra-structural changes of two strains exposed to both high and Sub-inhibitory concentrations of danofloxacin for 2 hours were observed under scanning electron microscope. Shrinking of the cell membrane, rupture of cell wall, and vacuoles in the cell or even lysis of the cell were seen as the bacteria were hatched with 2MIC and 4MIC danofloxacin. When the exposed concentration was 0.5MIC, the Staphylococcus aureus became larger with irregular shape, decreased dense and a thick wall, and Escherichia coli presented elongation or even filamentation with or without vacuoles in the cell. The results indicated that the danofloxacin inhibited the DNA gyrase mainly.The novobiocin-Sepharose CL-6B affinity chromatography was prepared by Epoxy-activated Sepharose 6B and novobiocin to purifying DNA gyrase which were used for determining the half inhibitory concentration ( ICJO ) of danofloxacin against DNA gyrase. The results showed that the 50% inhibitory concentrations (ICJO) of danofloxacin was 1.38 V- g/ml, and the period...
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